Explanation:

Mammography is not useful in women under the age of 35 with current techniques because the breast tissue is too dense to allow accurate interpretation of the x-rays. The general flow of diagnoses of a breast mass is to first do a needle aspiration, and then if necessary proceed to a biopsy. Mastectomy will be nearly the final step if the mass is proved to be malignant.

Explanation:

Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones (hypothyroidism).
Children with hypothyroidism may develop excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, exaggerated jaundice, and low body temperature. Physical features may include a larger anterior fontanel, persistence of a posterior fontanel, an umbilical hernia, and a large tongue (macroglossia).
In the developed world, nearly all cases of congenital hypothyroidism are detected by the newborn screening program. These are based on measurement of TSH or thyroxine (T4) on the second or third day of life. If the TSH is high, or the T4 low, the infant´s doctor and parents are called and a referral to a pediatric endocrinologist is recommended to confirm the diagnosis and initiate treatment. The goal of newborn screening programs is to detect and start treatment within the first 1-2 weeks of life. Treatment consists of a daily dose of thyroxine, available as a small tablet. Down´s syndrome (Trisomy 21), Edwards´s syndrome (Trisomy 18) and Patau syndrome (Trisomy 13) would not present like this.

Explanation:

Huntington´s disease has autosomal dominant inheritance, meaning that an affected individual typically inherits one copy of the gene with an expanded trinucleotide repeat (the mutant allele) from an affected parent. It has CAG repeats that increase in the number of repeats (and hence earlier age of onset and severity of disease) in successive generations known as genetic anticipation.

Explanation:

This is a classic presentation for Turner syndrome. In Turner syndrome (gonadal dysgenesis), girls are born with one of the two X chromosomes partially or completely missing. A karyotype will reveal her chromosome profile to be 45,X.
Girls with Turner syndrome have a webbed neck, a low hairline at the back of the neck, a broad chest with wide-spaced nipples, and poorly developed nails.
As a girl with Turner syndrome gets older, she has no menstrual periods (amenorrhea), and the breasts, vagina, and labia remain childlike rather than undergoing the changes of puberty. A girl or woman with Turner syndrome is virtually always short; obesity is common.

Explanation:

Congenital adrenal hyperplasia is a group of genetic disorders, each characterized by inadequate synthesis of cortisol, aldosterone, or both. The salt-wasting form causes hyponatremia (sometimes severe), hyperkalemia, and hypotension as well as virilization. If undiagnosed and untreated, this form can lead to life-threatening adrenal crisis, with vomiting, diarrhea, hypoglycemia, hypovolemia, and shock.
Very young female infants with the salt-Wasting form will have ambiguous external genitals, with clitoral enlargement, fusion of the labia majors, and a urogenital sinus rather than distinct urethral and vaginal openings. Male infants typically have normal sexual development. When the enzyme deficiency is much milder, neonates have little or no virilization, but androgen excess manifests later with early appearance of pubic hair and increase in growth velocity in both sexes, clitoral enlargement in (girls, and penile enlargement and earlier deepening of voice in boys.

Explanation:

In Turner syndrome (gonadal dysgenesis), girls are born with one of the two X chromosomes partially or completely missing.
Many newborns with Turner syndrome have swelling (lymphedema) on the backs of their hands and tops of their feet. Swelling or loose folds of skin are often evident over the back of the neck. Many other abnormalities often develop, including a webbed neck, a low hairline at the back of the neck, a broad chest with wide-spaced nipples, and poorly developed nails.
As a girl with Turner syndrome gets older, she has no menstrual periods (amenorrhea), and the breasts, vagina, and labia remain childlike rather than undergoing the changes of puberty. The ovaries usually do not contain developing eggs. A girl or woman with Turner syndrome is virtually always short; obesity is common.
Other disorders often develop. Heart defects include narrowing of part of the aorta (coarctation of the aorta). Kidney and eye defects, diabetes mellitus, and thyroid diseases are common.

Explanation:

The most common abnormality seen in a primary caregiver´s office in children younger than 12 years is a unilateral breast mass corresponding to asymmetric-breast development. One breast commonly develops earlier than the other. Ultimately, the breasts are symmetric, despite the discrepancy in the initial development.
Breast asymmetry may develop as thelarche ensues. In this condition, one breast may develop before or more rapidly than the other. The physical examination finding usually include homogenous enlargement of one breast with no discrete masses or discharge. Accompanying breast tenderness may be present if the breast bud is starting to develop. If a mass is excluded either by physical examination or ultrasonography; the patient and parents can be reassured that the asymmetry will become less noticeable with age.

Explanation:

Infants with cystic fibrosis are most prone to develop meconium impaction as a result of lack of pancreatic enzymes in the intestinal tract. Hyaline membrane disease, prematurity, Necrotizing eneterocolitis, and homocystinuria, an inborn error of metabolism, are not associated with meconium impaction.

Explanation:

Vitamin E toxicity may cause a necrotizing enterocolitis and hepatitis in children. Vitamin K toxicity although uncommon, may cause vomiting and hemolysis, as well as albuminuria and hemoglobinuria. Vitamin D toxicity is associated with hypercalcemia, as well as constipation, and sometimes nephrocalcinosis. Pantothenic acid toxicity is associated with diarrhea. Pyridoxine toxicity, while very rare, is associated with peripheral sensory neuropathy.

Explanation:

Vitamin C overdose may cause a decrease in copper absorption or a rise in the excretion of oxalic acid. Although thiamin toxicity is very rare, the potential adverse effects include an anaphylactic response and/or respiratory depression. There are no significant toxicities associated with biotin overdose. Vitamin A toxicity may cause pseudotumor cerebri, or retching associated with a rise in intracranial pressure. Vitamin K overdose shows no toxicity except for the product Menadione which is banned by FDA due to allergic reactions, hemolytic anemia, and cytotoxicity in liver cells.

Explanation:

There are no significant toxicities associated with biotin overdose. Although thiamin toxicity is very rare, the potential adverse effects include an anaphylactic response and or respiratory depression. Vitamin A toxicity may cause pseudotumor cerebri, or retching associated with a rise in intracranial pressure. Niacin overdose may cause anaphylaxis due to histamine release; also, cholestatic jaundice, cutaneous vasodilation, and cardiac arrhythmias may arise. Finally, vitamin C overdose may cause a decrease in copper absorption or a rise in the excretion of oxalic acid.

Explanation:

Werner´s syndrome is a DNA-repair disease stemming from mutated DNA helicase genes. It is characterized by an accelerated and premature onset of aging.

Explanation:

Full rapid replacement of thyroxine is critical in children to allow normal mental and physical development. Gradual replacement therapy is indicated in older people or those with known coronary artery disease. Dietary supplements and vitamin therapy are not helpful. Treatment is critical.

Explanation:

Pyruvate dehydrogenase (PDH) catalyzes the irreversible conversion of pyruvate to acetyl-CoA. If PDH is absent, pyruvate will be used in other pathways instead. Pyruvate will be converted to alanine via alanine aminotransferaseand to lactate via lactate dehydrogenase.
Glutamate dehydrogenaseis involved in oxidative deamination, releasing ammonium ion for urea synthesis. Deficiency of this enzyme would not cause the symptoms described. Phenylethanolamine N-methyltransferase is an enzyme involved in the synthesis of epinephrine. Deficiency of this enzyme would not cause the symptoms described.

Explanation:

Sickle cell anemia arises due to the mutation in the beta-globin gene. Because both of the beta-globin genes have to be abnormal to produce the disease, it is an example of autosomal recessive inheritance. When both parents are carriers of the abnormal gene (sickle-cell trait), the risk of having a child with disease (two abnormal genes; sickle-cell anemia) is 25%. The probability of having a child who is a carrier (one abnormal gene; sickle-cell trait) is 50%, and the probability of having a child who is normal (no abnormal gene) is 25%.
Certain congenital anomalies follow multigenic inheritance (non-Mendelian inheritance). Examples include Hirschsprung disease, pyloric stenosis, cleft lip, and other common congenital malformations. The recurrence risk in the second offspring after one affected child is in the range of 5% for such disorders. In diseases that follow autosomal dominant inheritance, the risk to the child where one parent is affected is 50%. Examples of such disorders include polycystic kidney disease and Huntington chorea. Under rare circumstances, the risk to the offspring can be higher than 50% in diseases with Mendelian inheritance. For example, if in the index case, both parents have sickle cell anemia (homozygous state); the risk to the offspring will be 100% because none of the beta-globin genes is normal.

Explanation:

This patient´s diagnosis is Turner syndrome. Patients present with characteristic physical Findings of short stature, webbed neck, shield-like chest with widely spaced nipples, and no secondary sexual characteristics. In Turner syndrome, follicle- stimulating hormone is high and so are luteinizing hormones, while estradiol is low. Turner syndrome patients also get buccal smear that shows normal-appearing epithelial cells, but without Barr bodies. There is no progesterone withdrawal bleeding because there is no estrogen. Turner syndrome patients have normal intellectual function. Treatment is estrogen replacement therapy, which will cause normal secondary characteristics to develop. These patients are infertile.

Here are the findings in Turner syndrome:

• High follicle-stimulating hormone
• High luteinizing hormone
• Low estradiol
• Buccal smear shows normal-appearing epithelial cells with no Barr bodies
• Progesterone challenge does not cause withdrawal bleeding because there is no estrogen
• Normal intelligence

Explanation:

The patient described in this question has type l diabetes mellitus, which is associated with an increased risk for celiac disease (non-tropical sprue, gluten-sensitive enteropathy). Early diagnosis of celiac disease has the potential to reduce later complications of untreated sprue, such as growth failure, osteopenia, and intestinal lymphoma. For that reason, screening for celiac disease should be done in all patients who have type 1 diabetes, because the prevalence of celiac disease in patients who have type l diabetes is 3 to 6%. Other risk factors for celiac disease, in which screening should be done, are Down syndrome, chronic lymphocytic (Hashimoto) thyroiditis, selective IgA deficiency and a first-degree relative who has celiac disease. The recommended screening test for celiac disease is the measurement of serum tissue transglutaminase IgA (TTG) antibody, in conjunction with a measurement of total serum IgA. This test has a sensitivity of 95%, although it may have false-negative results in patients who are IgA-deficient Anyone who has a positive TTG antibody test needs to have the diagnosis verified by way of endoscopy and duodenal biopsy, which would demonstrate varying degrees of inflammation and villous atrophy. Patients who have positive biopsy results must be placed on a lifelong gluten-free diet. Compliance can be documented by the return of TTG antibody levels returning to normal within 6 to 12 months.
Because celiac disease is a lifelong condition that requires permanent dietary restriction, empiric withdrawal of gluten from the diet without a definitive diagnosis is not appropriate. The anti-gliadin antibody test has poor specificity (large number of false-positives), and therefore it should not be used regularly for screening.

Explanation:

This neonate has the typical clinical presentation of congenital hypothyroidism. The most appropriate screening tests to diagnose this disorder would be to measure total T4 and thyrotropin levels. Congenital hypothyroidism results from a deficiency of thyroid hormone. Congenital hypothyroidism occurs in approximately 1 in 4,000 births and is the most common treatable cause of mental retardation. The most common cause of congenital hypothyroidism is thyroid dysgenesis. This is caused by either complete absence hypoplasia/ ectopy of thyroid tissue. Congenital hypothyroidism is twice as com on in females. Symptoms appear gradually. Weak cough and prolonged jaundice may be the earliest sign. Generalized hypotonia, slow respiratory effort, coarse facial features, enlarged fontanelles, poor feeding, somnolence, a large tongue, constipation, and an umbilical hernia may be present The skin may be dry, cold, mid mottled. The lull clinical picture develops by 3-6 months of age. Growth mid development are retarded. The fontanelles stay widely open. Hair is coarse and brittle. Serum levels of total T4 are low, whereas thyrotropin (thyroid-stimulating hormone) levels are elevated. Newborn screening tests detect most cases of congenital hypothyroidism. Early diagnosis and treatment has greatly reduced the incidence of complications.
Hereditary defects in thyroid hormone biosynthesis is incorrect because these are all inherited in an autosomal recessive pattern. For this choice to be correct, the child would have family history of thyroid disease, which is not mentioned in the stem.
Moreover, this is not a common cause of congenital hypothyroidism. . Among the hereditary defects, the most common is a defect in thyroid peroxidase enzyme activity that causes impaired iodide oxidation and organification.
Iodine deficiency and transplacental transfer of blocking antibodies (TRA-Ab) can cause transient congenital hypothyroidism. TRA-Ab occurs only in infants of mothers with autoimmune thyroid disease. The mother in this question does not give any such history.
Pituitary hypothyroidism is not a common cause of congenital hypothyroidism. Thyroid dysgenesis is much more common.
Transplacental transfer of insulin is incorrect for two reasons. First, insulin does not cross the placenta. Second, even if it did, it would not cause hypothyroidism. Insulin has nothing to do with hypothyroidism.

Explanation:

Explanation:

The patient described in the question has signs of metabolic syndrome and is most at risk for developing hypertension and obesity into adulthood. The criteria for metabolic syndrome is having a body mass index (BMI) of greater than 30 kg/m2 plus two of the following:

• Fasting triglyceride level >150 mg/dL
• High-density lipoprotein cholesterol <40 mg/dL
• Hypertension (e.g., systolic BP >130 mm Hg and diastolic BP >85 mm Hg)
• Fasting plasma glucose >100 mg/dL

Acanthosis nigricans is not included as a criterion for the diagnosis of metabolic syndrome, although it is often found.
Maternal or family history of diabetes is frequently found, and although it does increase the chances of developing type 2 diabetes in the child, it is not one of the criteria for the diagnosis of metabolic syndrome.

Explanation:

Part of the physical examination of every newborn is a gross examination of the eyes and a retinal examination to detect a red reflex, indicating that there are no structures preventing light from falling on the retina. There may be loss of the normal transparency of the cornea due to hereditary factors or environmental effects. A cataract is any opacity of the lens, and may significantly affect vision. The differential diagnosis is large and includes developmental variants, genetic disorders, endocrinopathies, congenital infections, ocular anomalies, and idiopathic causes. Of the diagnoses listed for this ponticular patient, the only one that is seen with cataracts is galactosemia. Other inborn errors of metabolism may also present with cataracts, such as homocystinemia, Fabry disease (alpha- galactosidase A deficiency) , Niemann-Pick disease (sphingomyelinase deficiency), abetalipoproteinemia (absent chylomicrons) , Refsum disease (phytanic acid alpha-hydrolase deficiency) , mannosidosis (acid alpha- mannosidase deficiency), and Wilson disease. Wilson disease, however, will not manifest at birth.
Of the congenital infections, mumps is not associated with cataracts. The infections that may present with cataracts are rubella, syphilis, CMV, toxoplasmosis, herpes simplex, measles, varicella-zoster, influenza, and polio.
Maple-syrup urine disease is not one of the inborn errors associated with congenital cataracts.
A ponticular type of lens change may be seen in some preterm infants a cluster of tiny vacuoles in the distribution of the Y sutures on the lens. These need to be seen with the ophthalmoscope with the pupil dilated. The patient in the question, however, is not preterm.

Explanation:

The patient described above has Gaucher disease (GD), which is an autosomal recessive, lysosomal storage disorder. Caused by the deficiency of the enzyme glucosylceramidase, GD results in the accumulation of glucosylceramide and other glycolipids.
A subset of patients with GD is asymptomatic, and has painless hepatosplenomegaly, possibly with elevated transaminases.
Thrombocytopenia and anemia are often seen in these patients. Most effected individuals also suffer from bone abnormalities, which can include pain crisis, avascular necrosis, osteoporosis, fractures, and even abnormal modeling with widening of the distal femurs. If these children are left untreated, they are at high risk of developing splenic infarctions, severe hepatosplenomegaly, growth, and development delay and pulmonary infiltration. The management of GD, type 1, is via enzyme replacement therapy.
Alpha-mannosidosis has more than one form and includes mental retardation as a feature.
Hunter syndrome, an X-linked mucopolysaccharidosis (MPS II), has mild and severe forms, both of which re associated with coarse facial features and characteristic bone abnormalities.
Niemann-Pick disease, type A, my present with hepatosplenomegaly s early as birth and is associated with failure to thrive and neurologic deterioration, which usually results in death during the first few years of life.
Sanfilippo disease, type B (MPSIII B) is associated with developmental delays, variable coarsening of the facial features, and progressive CNS deterioration.

Explanation:

The majority of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, and most of these are the classic, salt-losing form. Due to a deficiency of the enzyme, there is a block in the biosynthesis of cortisol and aldosterone. Because of this, prior to the block there is a buildup of the major substance, which is 17-hydroxyprogesterone, and shunting of the pathways to androstenedione, which is then converted to testosterone. The major effect of this is virilization in female fetuses. One generally finds clitoral enlargement, partial or complete labial fusion, and a urogenital sinus (vagina and urethra with common opening). If undiagnosed at birth (which would happen in a male), the baby develops progressive weight loss, weakness, vomiting, dehydration, hypoglycemia, hyperkalemia, and hyponatremia, resulting in cardiac arrhythmias, shock, and death. If untreated, affected patients develop further virilization alter birth due to postnatal androgen excess-accelerated growth and skeletal maturation resulting in early epiphyseal closure and premature pubertal changes. Diagnosis is established by measuring 17-hydroxprogesterone in the blood before and after stimulation with a cortisol derivative.
The main goal of management in subsequent pregnancies is to prevent masculinization of affected females. Treatment of any at-risk pregnancy is to administer dexamethasone to the mother beginning no later than 6 weeks gestation. Dexamethasone crosses the placenta and will suppress fetal adrenal steroid secretion and prevent masculinization. CVS is then performed to determine the genotype, and therapy is continued if ` it is female. Therapy is then continued until genetic analysis confirms the absence of abnormal genes. The mother must be followed carefully for steroid side effects. There is no deleterious effect on the unaffected fetus.
The major point in the management of a baby born with ambiguous genitalia is that the patient must be evaluated and monitored for the possibility of a salt-losing crisis; however, when there is a positive family history, we do not simply await the birth of subsequent child (as explained above). A reasonable approach to the initial evaluation of a newborn with ambiguous genitalia is: (1) perform a thorough examination to look for other anatomic abnormalities and to define the genital anatomy, locate the urethral meatus, and palpate the scrotum, inguinal areas, and labia for gonads (usually indicates testes and a genetic male); (2) perform an ultrasound to try to locate gonads and determine if there is a uterus; (3) obtain blood for a karyotype to determine the genotype; and ( 4) inject contrast into the urogenital sinus of females to demonstrate a uterus and vagina and to assist the surgeon with surgical management. After this; specific hormonal studies may be obtained (obtaining the results will take longer). Thus, the parents can at least be told the genetic sex and the internal anatomy.
The neonatal screen for 21-hydrowyiase deficiency involves performing a heel-stick puncture and placing the blood on a filter paper card (as part of the general newborn screening for other congenital disorders). The test screens for elevated levels of 11-hydroyprociesterone, but there are many false negatives. Any positive result requires that the infant have a blood 17- hydroxyprogesterone level at 2 weeks of age. The disorder may be diagnosed prenatally with chorionic villus sampling (CVS) in the late first trimester or in the second trimester by amniocentesis. Although these will diagnose the condition (when there is a previous child born with the condition), one can not wait this long for the results because shunting to androstenedione will already have begun. High-resolution ultrasound can certainly follow genital development, but for the reasons stated above, therapy must be instituted early.
For those children diagnosed with the disorder alter birth, therapy is with glucocorticoids (hydrocortisone) for the cortisol deficiency and mineralocorticoid replacement (fludrocortisone) for salt-wasting disease. Females who have been significantly virilized undergo surgery in the first year of life.

Explanation:

This patient has a pituitary adenoma, as indicated by the neurologic complaints of headaches and visual disturbances (bitemporal loss of vision, suggested by the lamppost collisions while driving). Impaired vision, the most common symptom that leads a patient to seek medical attention, is caused by suprasellar extension of the adenoma that compresses the optic chiasm. The most common complain is diminished vision in the temporal fields (bitemporal hemianopsia). Headaches and diplopia, (due to oculomotor nerve compression) are other common complaints. Pituitary adenomas can cause overproduction (more common and most frequently prolactinoma) or underproduction of hormones (most frequently luteinizing hormone [LH]).
Many patients with sellar masses admit to symptoms of pituitary hormone deficiencies at the time of initial presentation of pituitary adenoma. But these symptoms do not usually bother the patient. LH deficiency ultimately leads to a decreased serum androgen concentration, which produces symptoms of decreased energy, decreased libido, and loss of axillary and pubic hair in both men and women. In women, there is amenorrhea. Breast atrophy is seen only in chronic deficiency.
Excessive production of androgens in a female results in virilization, which means excessive male-pattern hair growth in a woman (hirsutism) plus other masculinizing signs (such as clitorimegaly, baldness, lowering of the voice, increasing muscle mass, and loss of female body contours); The conditions responsible for excess androgen production are adrenal tumor, ovarian tumor (Sertoli-Leydig), congenital adrenal hyperplasia, and polycystic ovarian syndrome. Excessive production of estrogens would produce feminization in a male (gynecomastia, for instance). A high level of prolactin is incorrect, as this patient does not have galactorrhea. Prolactinomas produce:
In either sex: hypogonadism (decreased libido and loss of axillary and pubic hair), if hyperprolactinemia is sustained. In women: amenorrhea, galactorrhea, and infertility

• In men: decreased libido, impotence, and galactorrhea (rarely).

Insufficient production of estrogens would have inhibited the development of this patient´s breasts.

Explanation:

Type 2 diabetes mellitus (DM) is an increasing problem in adolescence, and mostly in the markedly obese. The problem is usually insulin resistance and secondary hyperinsulinemia over time, hyperglycemia worsens and is accompanied by hyperlipidemia often the symptoms are not as dramatic as those with type 1 DM, and do not usually present with diabetic ketoacidosis (DKA.). DKA may, however, occur with the stress of another illness. Over time, one may see the typical microvascular and macrovascular complications if the hyperglycemic state continues. The presence of acanthosis nigrans, as in this question (darker pigmentation in skin creases and flexural areas), is seen in the majority of patients with type 2 DM. The accepted criterion for diagnosing DM is lasting plasma glucose greater than 126 mg/dL. A fasting glucose of 109 mg/dL is the upper limit of normal, and therefore values between this and the minimum for DM represent the term impaired glucose tolerance. An abnormal screen should be followed with an oral glucose tolerance test. Impaired glucose tolerance is a risk factor for future DM and cardiovascular disease and is associated with the insulin resistance syndrome, or syndrome X. This consists of insulin resistance, compensatory hyperinsulinemia, obesity, dyslipidemia, and hypertension. Thus, in the present case, the patient is obese, is mildly hypertensive, has acanthosis, and needs to be screened for impaired glucose tolerance or DM as the most important initial step in management.
Nutritional education is the mainstay of therapy, and the initial therapy should be that of weight loss and increasing exercise. If the patient is diagnosed with DM, depending on the presentation, he may need insulin therapy (the only universally accepted therapeutic agent in children) in combination with metformin (a biguanide that decreases hepatic glucose production), but these may be reduced or discontinued after the patient is in good glucose control. Certainly, in the present question, the increased blood pressure needs to be confirmed and repeated measurements on subsequent visits are important. The BP is mildly elevated and should improve with weight reduction. Medications are typically not necessary unless the hypertension is severe. One should not be confused by the presence of abdominal striae. This is a very common finding in obese patients and should not immediately suggest a diagnosis of adrenal insufficiency.

Explanation:

Explanation:

This infant presents with ambiguous genitalia and hypovolemic shock secondary to electrolyte abnormalities. These are the cardinal clinical features of the salt-wasting form of-congenital adrenal hyperplasia (CAH), and they are the cause of 90% of CAH cases. Deficiency of 21-hydroxylase enzyme results in low or absent plasma cortisol and aldosterone and a compensatory´ ACTH elevation. The following upstream precursors accumulate: progesterone, 17- hydroxyprogesterone, androstenedione, androgens, and dehydroepiandrosterone (DHEA), a weak androgen that masculinizes the affected female infant. The decreased secretion of aldosterone results in salt loss with hyponatremia and hyperkalemia. Elevated basal 17- hydroxyprogesterone levels are diagnostic of 21-hydroxylase deficiency related to CAH. It is important to note that patients do not require confirmatory studies to treat with glucocorticoids because prompt administration may be life-saving.
A deficiency of 5-alpha reductase and an elevated testosterone dihydrotestosterone (DHT) ratio are diagnostic of male under virilization (also called pseudovaginal perineoscrotal hypospadias), which is an autosomal recessive disorder associated with failure of DHT formation that results in normal internal male derivatives but in utero failure of external genitalia virilization. It is often not diagnosed until puberty. This infant however, has normal female internal structures making this condition unlikely.
Imaging studies of the adrenal gland are generally not useful in the evaluation of adrenal hyperplasia. A CT scan of the abdomen may be used in patients without ambiguous genitalia and who present with acute adrenal failure to exclude the possibility of bilateral adrenal hemorrhage.
Maternal androgen levels may be elevated in female pseudohermaphroditism, a disorder where a chromosomal female has virilized external genitalia secondary to androgens in the maternal circulation. However, the presence of electrolyte abnormalities and shock suggest CAH as the cause of this infant´s virilization. A Serum estrogen level and serum LH levels are normal and serve no diagnostic utility´ in CAH.

Explanation:

The metabolic syndrome is a series of clinical and laboratory findings that include truncal obesity, elevated concentrations of serum triglycerides, decreased concentrations of high-density lipoprotein (HDL) cholesterol, and an elevation in blood pressure. Patients who have metabolic syndrome are at an increased risk for developing type 2diabetes and cardiovascular disease. The patient described has abdominal obesity, hypertension, and a family history of type 2 diabetes, which places him at a higher risk for cardiovascular disease as he ages.
Insulin resistance, which is often found in metabolic syndrome, may lead to hyperglycemia, not hypoglycemia C-reactive protein and fibrinogen values are often elevated in patients who have metabolic syndrome.
The most likely laboratory abnormalities to be identified with the metabolic syndrome are elevated triglyceride concentrations and decreased concentrations Of HDL cholesterol, not low triglycerides and high LDL.

Explanation:

Parents of a child who has Down syndrome have an increased risk of having a second child with the same disorder. The age-related risk of the mother is 1% after age 35 years. The general risk of parents having a second child who has the disorder is 1%; therefore, the risk of any parents having a second child who has Down syndrome is 1% plus the age-related risk of the mother. In this case the mother being younger than age 35 years has an age-related risk of 0.1%, so her risk of having a second child who has Down syndrome is 1.1 %. Approximately 94% of individuals who have Down syndrome have a trisomy of chromosome 21, usually caused by nondisjunction of the maternal chromosomes. If a meiotic error occurred once, it has a likelihood of occurring again. There is therefore a higher risk for having a second child who has Down syndrome if a set of parents already have one child with that disorder.

Explanation:

The disease is Wilson disease; an autosomal-recessive disease caused by a mutation in ATP/B, a gene that code for a P type ATPase, which transports copper into bile. This impaired excretion of copper causes a buildup of copper that can lead to neurologic (psychiatric symptoms, bradykinesia and rigidity, tremors, or chorea) and hepatic (hepalitis, cirrhosis, or asymptomatic liver function test abnormalities) findings. The corneal rings described in the question stem are the pathognomonic Kayser Fleischer rings that result from copper deposition. Treatment is with lifelong administration of the copper chelating agent penicillamine. Deferoxamine is used parenterally to chelate circulating iron. EDTA is an effective chelator of divalent (and trivalent) cations such as lead. Lithium is used to treat bipolar disorder. Phenobarbital is used to treat epilepsy.

Explanation:

The majority of children with failure to thrive (FTT) have no laboratory abnormalities. In a classic study of children hospitalized with FTT, only 1.4% of laboratory tests were of diagnostic significancs. A practical approach is not to order any laboratory test initially unless suggested by the history or physical examination. Screening laboratory studies can be considered in considered in children who fail to respond to nutritional intervention.

Explanation:

Some gynecomastia occurs in 30%-50% of pubertal males. It typically appears between 12 and 15 years of age, at Tanner stages 2 and 3. Physiologic gynecomastia is usually mild and may be either unilateral or bilateral. Breast tenderness is common and also mild. The enlargement typically regresses within a few months to 2 years. Serum hormone levels are the same as in boys without gynecomastia, although the ratio of testosterone to estrogen is lower than in males at similar stages without the condition. There is no indication for chromosomal investigation or radiography. A biopsy should be considered only if the condition persists beyond mid-puberty.

Explanation:

In the Tanner I stage, male genitalia of childhood size, as well as the absence of public hair, are noted. The transition of tanner I to Tanner II stage denotes the growth of the testicles as well as the formation of sparse, long public hairs. The public hairs gradually grow longer and coarser in the tanner III stage, and the hairs cover the pubis in the Tanner IV stage. It is not until the Tanner V stage that the hair begins to grow on the lateral aspects of the thigh, indicating that adult quantities and distribution of public hairs have been achieved.

Explanation:

In G6PD deficiency, a sex-linked condition, with the gene located on the X chromosome, the red blood cell is unable to protect itself from oxidative damage. Oxidation of hemoglobin produces intracellular precipitates of denatured hemoglobin, known as Heinz bodies. The G6PD activity declines approximately 50% as the red cell ages. Some foods are agents that precipitate attacks of jaundice in G6PD deficiency. The most frequently cited food is the fava bean, which generates oxidants when metabolized. Favism is endemic in the Mediterranean, Middle East, and parts of Africa where consumption is prevalent. Both infections (viral as well as bacterial) and the oxidant drugs implicated are numerous, including antimalarials (e.g., primaquine and chloroquine), sulfonamides, nitrofurantoins, and others

Explanation:

The pubic hair in boys reaches its maximum quantity and distribution (resembling that of an adult male) at approximately 15 years of age, coinciding with maximal genitalia size and maximal height spurt in adolescent boys.

Explanation:

Werner´s syndrome is a DNA-repair disease stemming from mutated DNA helicase genes. It is characterized by an accelerated and premature onset of aging.

Explanation:

Lesch-Nyhan syndrome was described in 1964 in two brothers who manifested self-mutilative behavior, choreoathetosis, and mental retardation beginning in their first year of life. This X- linked hereditary disorder is due to complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), an enzyme that catalyzes the “salvage” pathway of purines, A salvage pathway deficiency results in increased de-novo synthesis of purines, with consequent overproduction of uric acid. This is why patients with deficient HPRT develop hyperuricemia, with secondary uric acid stones, renal impairment, and gouty arthritis. Lesch-Nyhan syndrome is also characterized by self-mutilative behavior (bite marks on fingers and forearms), choreoathetosis, and mental retardation; these manifestations are still largely unexplained. Renal failure is the most frequent cause of death. Definitive diagnosis is obtained by measurement of HPRT enzyme activity in blood or tissue. The diagnosis can be further confirmed by identifying a molecular genetic mutation in the HPRT gene.
Both 24-hour urinary uric acid excretion (choice A) and blood uric acid level will be elevated in Lesch-Nyhan syndrome because patients develop hyperuricemia due to HPRT deficiency, leading to gouty arthritis. Thus, these tests could be some initial steps in the diagnosis/management of this condition. But both of these tests lack specificity, as hyperuricemia could be present in many other conditions. Thus, these two choices are incorrect because they cannot confirm the diagnosis.
Blood lead level is incorrect, as the vignette gives the typical picture of Lesch-Nyhan syndrome. Chronic lead intoxication A affects the nervous, gastrointestinal, and hematopoietic systems. Behavioral anomalies, hypochromic microcytic anemia, and peripheral neuropathies are the most common manifestations. Children are particularly vulnerable to lead intoxication. Skeletal survey for suspected child abuse is incorrect because the vignette gives the typical picture of Lesch-Nyhan syndrome.
The bite marks here are due to self-mutilating behavior and not to child abuse. Moreover, a diagnosis of child abuse does not explain the other findings of arthritis, repeated nephrolithiasis, and progressive renal failure.
Urine for mucopolysaccharidoses is used to test for the diagnosis of Hunter syndrome. Patients with Hunter syndrome present differently. They tend to have short necks, broad chests, a protuberant abdomen, hepatosplenomegaly, umbilical hernia, thoracolumbar kyphosis, decreased joint mobility, claw like fingers, and stiff gait Short stature is usually detected after 3 years of age.

Explanation:

The child presented here has Prader-Willi syndrome, which is characterized by low birth weight, almond-shaped palpebral fissures, and hypogonadism. Conducting agenetic test such as florescent in situ hybridization test for the gene locus at the 15q11- 13 chromosomal region provides the definitive diagnosis. The main clue to this diagnosis based on physical examination is the hypotonia, which can be found in a variety of disorders.

• Cerebral or central causes of hypotonia include chromosomal abnormalities, such as Down syndrome, Turner syndrome, and Prader-Willi syndrome. Metabolic causes of hypotonia include hypothyroidism and leukodystrophies. Sepsis and perinatal trauma (hypoxia-ischemia or intracranial hemorrhage) are also causes of hypotonia in the newborn period. Deep tendon reflexes are normal.
• Spinal causes of hypotonia are the most worrisome and may be caused by spinal muscular atrophy. Deep tendon reflexes are diminished or absent.
• Peripheral hypotonia results from neuromuscular junction abnormalities, which include botulism, myasthenia gravis, or myasthenic syndrome. Deep tendon reflexes are absent or decreased.
• Neuropathic causes of hypotonia in infants are rare, but include congenital polyneuropathy and familial dysautonomia. Arylsulfatase A testing assesses for metachromatic leukodystrophy, which would typically develop alter the first year of life.

EMG and nerve conduction studies would be used to assess a congenital myopathy or spinal muscular disorder. According to the classification above, the physical examination does not support this diagnosis.
MRI of the brain would be done to evaluate for any head trauma or cerebral dysgenesis, but the history does not support such a diagnosis.
Thyroid-stimulating hormone is not likely to be abnormal in this child, because he is not displaying any other signs or symptoms of hypothyroidism.

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Males are twice as likely to have a cleft lip with or without cleft palate. Cleft palate without cleft lip is more common in females.

Explanation:

Dehydration is significant depletion of body water and, to varying degrees, electrolytes. Symptoms and signs include thirst, lethargy, dry mucosa, decrease urine output, and as the degree of dehydration progresses, tachycardia, hypotension, and shock. Diagnosis is based on history and physical examination.
Treatment is best approached by considering separately the fluid resuscitation requirements, current deficit, ongoing losses, and maintenance requirements. The volume (e.g., amount of fluid), composition, and rate of replacement differ for each. Formulas and estimates used to determine treatment parameters provide a starting place, but treatment requires ongoing monitoring of vital signs, clinical appearance, urine output and specific gravity, weight, and sometimes serum electrolyte levels.
Children with severe dehydration (e.g., evidence of circulatory compromise) should receive fluid IV. Those unable or unwilling to drink or who have repetitive vomiting can receive fluid replacement IV, through an NGT, or sometimes orally through frequently repeated small amounts.

Explanation:

In boys, facial, axillary, and pubic hair appears and the penis grows, with or without enlargement of testes. In girls, breasts develop, and pubic hair, axillary hair, or both appear. Girls may begin to menstruate. Body odor, acne, and behavior changes may develop in either sex. Height growth is initially rapid in both sexes, but premature closure of the epiphyses results in short adult stature. Testicular or ovarian enlargement occurs in precocious puberty but is usually absent in isolated precocious adrenarche.
Diagnosis is clinical. X-rays of the left hand and wrist are done to assess skeletal maturation and check for accelerated bone growth. Unless history and examination suggest an abnormality, no further evaluation is required for children with pubertal-milestones that are within l year of population standards or for girls and boys with precocious adrenarche and girls with precocious thelarche as long as x- rays confirm that bone growth is not accelerated.
When further evaluation is necessary, the following serum hormones may be measured: β-human chorionic gonadotropin, estradiol, testosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, LH, follicle-stimulating hormone (FSH), and prolactin. Pelvic and adrenal ultrasonography and MRI or CT of the brain may be done.

Explanation:

Hypothyroidism is associated with markedly delayed bone age relative to height age and chronologic age. In cystic fibrosis, bone age and height age are equivalent, but both lag behind chronologic age. Children with chromosomal anomalies such as trisomy 21 (Down syndrome) or XO have a height age which is delayed relative to bone age. This pattern is also seen as a result of maternal substance abuse.

Explanation:

This patient has cystic fibrosis (CF), as indicated by the present respiratory tract infection, past history of neonatal jaundice, and recurrent episodes of bronchiolitis, growth retardation, and nasal polyps. Other findings that should make you think of CF include chronic diarrhea, features of malabsorption, meconium ileus, recurrent sinus infection, failure to thrive, and family history of CF. The CF gene is located on chromosome 7 and codes for a protein called cystic fibrosis transmembrane conductance regulator (CFTR). A defective CFTR leads to an abnormality of chloride transport that produces abnormally thick mucus, resulting in lung, gastrointestinal, sweat gland, biliary, and genitourinary system problems. Patients with CF have an elevated salt content in their sweat and other secretions, difficulty clearing abnormally viscous mucous secretions, and chronic lung infections. The most appropriate initial diagnostic test is the sweat chloride test. Respiratory manifestations, include a persistent, productive cough; hyperinflation of the lung fields on chest radiograph; and pulmonary function tests that are consistent with obstructive airway disease. As the disease progresses, chronic bronchitis with or without bronchiectasis develops and is , accompanied by acute exacerbations characterized by increased cough, tachypnea, dyspnea, increased sputum production, and weight loss. Digital clubbing is often seen in patients with moderate to advanced disease. Acute pulmonary exacerbations are treated with antibiotics alter sputum culture. Intravenous antibiotics re indicated when there is:

• Tobramycin plus a carbapenem (e.g., imipenem/cilastatin or meropenem) CFTR gene mutation analysis may be used as an adjunct for diagnosis in atypical cases, but it is not widely available and cannot (be considered the most appropriate initial diagnostic study. Moreover, this patient has an SaCO2 of 98% and is tachypneic. She needs to be treated first with IV antibiotics, and then the diagnosis of cystic fibrosis can be established.

Histopathologic analysis of the nasal polyps yields no characteristic findings and is not used in the diagnosis of CF.
Although levofloxacin is used in community-acquired pneumonia and has activity against some gram-negative bacilli such as P. aeruginosa, it is not approved for systemic use in children.
Oral antibiotics are appropriate if the exacerbation is relatively mild, providing all pathogens identified are sensitive to available agents. This child has acute severe exacerbation of respiratory tract infection with a SaO2 of 90%, indicating, hospitalization and intravenous antibiotic therapy with strong pseudomonal coverage.
Pilocarpine iontophoresis test to measure sweat chloride is the best initial test to diagnose CF. To conduct this test, at least 50 mg of sweat must be collected within 45-minute period. But this choice is incorrect in this acute setting where the child is desaturating with severe pulmonary infection. She needs to be treated first. Since this child´s clinical presentation is highly suspicious for CF, sweat chloride and subsequent genetic mutation analysis will be warranted after the acute crisis has been handled.

Explanation:

This is Leigh´s disease, a rare condition also known as subacute necrotizing encephalomyelopathy. The underlying problem is a defective form of cytochrome C oxidase, an electron transport chain component, in the mitochondria of muscle and brain. Clinically, the features described in the question stem are seen. Pathologically, there is a symmetric necrosis that affects central areas of the nervous system from the thalamus to the spinal cord. No effective treatment exists at this time.
The Golgi apparatusis involved in packaging materials for secretion outside the cell. You should associate the mucolipidosis I-cell disease with Golgi apparatus problems. Lysosomes are the organelles that degrade many cellular products. Defects can produce a wide variety of lysosomal storage diseases, including Hurler and Hunter syndromes. Ribosomes are the organelles that translate mRNA into proteins. There are no known diseases of ribosomes, probably because their function is so crucial that any problems produce death in utero. Hypertrophy of the smooth endoplasmic reticulum in the liver is associated with conditions that stimulate the cytochrome P450 detoxification systems (e.g., barbiturate use and alcoholism).

Explanation:

Vitamin E toxicity may cause a necrotizing enterocolitis and hepatitis in children. Vitamin K toxicity although uncommon, may cause vomiting and hemolysis, as well as albuminuria and hemoglobinuria. Vitamin D toxicity is associated with hypercalcemia, as well as constipation, and sometimes nephrocalcinosis. Pantothenic acid toxicity is associated with diarrhea. Pyridoxine toxicity, while very rare, is associated with peripheral sensory neuropathy.

Explanation:

Persons deficient in cell mediated immunity will be able to defend against encapsulated bacterial infections because these organisms are battled by the humoral immune response. However, T cell deficient individuals will harbor an inability to defend against viral, fungal, and parasitic infections because these are attacked by T-lymphocytes. T cell deficient persons also demonstrate an increased risk for the development of malignancy, as well as growth retardation.

Explanation:

This baby girl has phenylketonuria, an autosomal recessive disorder that occurs with a frequency of 1:10,000. Phenylketonuria results from a defect in hydroxylation of phenylalanine to tyrosine. Affected infants are normal at birth until there is sufficient buildup of toxic metabolites. Newborn infants are asymptomatic prior to the initiation of feeds containing phenylalanine (e.g., breast milk or standard infant formula). Mental retardation is the most common manifestation and is very severe. Projectile vomiting occurs and may be confused with pyloric stenosis. Infants are photosensitive, fair-haired, and fair-skinned, and have blue eyes. An eczematous rash similar to atopic dermatitis develops in flexural areas in about 50% of these newborns. Commonly, there is a musty odor of body and urine due to the increased concentration of the metabolite phenylacetic acid. Routine newborn screening now detects the diagnosis before most children exhibit symptoms. After a positive test confirms phenylalanine hydroxylase deficiency, blood levels of phenylalanine (high) and tyrosine (normal) should be drawn.
Maple syrup urine disease (MSUD) is a familial cerebral degenerative disease caused by a defect in branched-chain amino acid metabolism .The most important diagnostic test for MSUD is the measurement of plasma amino acid (leucine, isoleucine, and valine) concentrations. MSUD is characterized by severe mental and motor retardation and by urine with a maple syrup-like odor. The presence of eczematous rash, photosensitivity, and musty odor to urine points toward the diagnosis of phenylketonuria.
Blood levels of glucose are abnormally low in infants born to diabetic mothers. Maternal hyperglycemia leads to fetal hyperglycemia, which in turn leads to fetal hyperinsulinemia. Insulin is a growth hormone and is responsible, with the hyperglycemia, for the pathophysiologic changes. These babies are large for gestational age, jittery, and excitable, and with tremors resulting from hypoglycemia (alter birth there is no increased glucose level from the mother, and the hyperinsulinemia persists). Hypertrophic cardiomyopathy, respiratory distress, hyperbilirubinemia, polycythemia, and congenital cardiac, skeletal, and gastrointestinal defects may be present as well. Even though the mother had gestational diabetes, the child´s presentations are in consistent with the features of fetal hyperglycemia.
Serum tyrosine (choice D) is elevated in tyrosinemia, an autosomal recessive syndrome resulting from deficiency of hepatic aminotransferase. Clinical features are mild to severe keratitis, mental retardation, and hyperkeratotic and erosive lesions of the palms and soles. A low-tyrosine, low-phenylalanine diet may improve or prevent the eye and skin lesions but may or may not prevent mental retardation.
Urine homogentisic acid (choice E) is elevated in newborns with alkaptonuria (ochronosis), an autosomal recessive trait caused by the lack of renal and hepatic homogentisic acid oxidase. Excretion of homogentisic acid in the urine leads to black-colored urine, with concurrent deposition of a grossly brown-black pigment in connective tissue and ochronotic arthropathy.

Explanation:

This patient is likely a new-on set type 1 diabetic, with a classic presentation of polyuria, polyphagia, polydipsia, and weight loss. The most common cause of type 1 diabetes is autoantibody production against pancreatic antigens, such as glutamic acid decarboxylase. These antibodies are present in over 70% of type 1 diabetics at the time of presentation and can be a useful test to help confirm the mechanism of disease in unclear cases. Elevated fasting cholesterol and triglyceride levels are commonly seen in type 2 diabetics and are manifestations of insulin resistance type l diabetic patients who have sudden failure of insulin secretion do not suffer from dyslipidemia that is as severe, particularly at the time of presentation.
Parotid gland hypertrophy and loss of teeth enamel are insensitive findings that suggest bulimia Dramatic weight loss is not common in bulimic patients, unless there is also an anorexic component and most patients directly or indirectly admit to self-image problems.
Proteinuria and retinal changes are later complications of diabetes and usually take at least a decade before becoming evident. They are unlikely to be found at the time of presentation.

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