A 2-week-old girl is admitted to the hospital for dehydration and vomiting. She had an uncomplicated vaginal delivery at home and did not undergo newborn screening. Breastfeeding has been difficult due to the newborn's lethargy and frequent vomiting. The mother has no medical problems, took no medications during the pregnancy, and had normal prenatal laboratory results. Family history is significant for a brother who died at age 1 month from severe dehydration several years ago. The newborn has a 2-year-old sister who is healthy. Vital signs show hypotension and tachycardia. Examination shows a sunken fontanelle and ambiguous genitalia. The rest of the examination is unremarkable. Abdominal x-ray, abdominal ultrasound, and upper gastrointestinal studies are normal. Karyotype analysis is pending. Serum chemistry results are as follows: A deficiency of which of the following is the most common cause of this patient's presentation?

Question

A 2-week-old girl is admitted to the hospital for dehydration and vomiting.  She had an uncomplicated vaginal delivery at home and did not undergo newborn screening.  Breastfeeding has been difficult due to the newborn's lethargy and frequent vomiting.  The mother has no medical problems, took no medications during the pregnancy, and had normal prenatal laboratory results.  Family history is significant for a brother who died at age 1 month from severe dehydration several years ago.  The newborn has a 2-year-old sister who is healthy.  Vital signs show hypotension and tachycardia.  Examination shows a sunken fontanelle and ambiguous genitalia.  The rest of the examination is unremarkable.  Abdominal x-ray, abdominal ultrasound, and upper gastrointestinal studies are normal.  Karyotype analysis is pending.  Serum chemistry results are as follows:   A deficiency of which of the following is the most common cause of this patient's presentation?

Quizplus · Accepted Answer

Explanation: 11ec2b69_beac_f8cf_8f63_5b28ca91606e_MD0005_00 Congenital adrenal hyperplasia (CAH) is a group of disorders characterized by a deficiency in an enzyme involved in steroid synthesis. Most cases are due to autosomal recessive inheritance of 21-hydroxylase deficiency. In addition to low production of mineralocorticoids and glucocorticoids, the deficiency of 21-hydroxylase results in an excess of its substrates. These excess substrates are shunted toward androgen synthesis, resulting in ambiguous genitalia in girls and precocious puberty in boys. Adrenocorticotropic hormone levels are also elevated and lead to hyperplasia of the adrenal glands, further contributing to the increased production of androgens. Salt-wasting syndrome occurs in severe deficiencies of 21-hydroxylase and presents in the first few weeks of life with life-threatening emesis, dehydration, and shock. Laboratory findings include hyponatremia and hyperkalemia (from lack of aldosterone) and hypoglycemia (from lack of cortisol). This patient's presentation and laboratory results are consistent with classic CAH. (Choices A and B) 11 β-hydroxylase and 17 α-hydroxylase deficiencies are rare causes of CAH and can be distinguished from 21-hydroxylase deficiency by the presence of hypertension. (Choice D) Galactosemia is an autosomal recessive disorder characterized by the inability to digest galactose due to deficiency of galactose-1-uridyl transferase. Patients are hypoglycemic and become very ill and dehydrated due to vomiting after ingestion of breast milk or cow's milk-based formula. However, these patients would not have hyperkalemia or ambiguous genitalia. (Choice E) Steroid 5 α-reductase deficiency is a rare autosomal recessive disorder that can cause 46,XY individuals to have external female-appearing genitalia, with clitoromegaly in some patients. Affected 46,XX patients have normal external female genitalia. Neither type would have electrolyte derangements as cortisol and aldosterone levels should be normal. Educational objective: The most common cause of congenital adrenal hyperplasia is 21-hydroxylase enzyme deficiency. Clinical features include ambiguous genitalia in 46,XX individuals, hyponatremia, hyperkalemia, hypoglycemia, and hypotensive shock. References: Congenital adrenal hyperplasia due to 21 hydroxylase deficiency: from birth to adulthood. (http://www.ncbi.nlm.nih.gov/pubmed/23044877) Congenital adrenal hyperplasia: issues in diagnosis and treatment in children. (http://www.ncbi.nlm.nih.gov/pubmed/24254335)

A 2-Week-Old Girl Is Admitted to the Hospital for Dehydration