A 5-month-old boy is brought to the emergency department with a 2-day history of projectile vomiting, diarrhea, and an episode of generalized tonic-clonic seizure activity just prior to arrival. He has been exclusively formula-fed since birth. He was born at 39 weeks gestation and had a "natural birth" at home. The pregnancy and delivery were uncomplicated. The boy did not undergo newborn screening due to parental preferences. His parents and 4-year-old sister are all healthy. One of his maternal uncles is intellectually disabled and lives in a long-term care facility. The boy's weight, height, and head circumference are at the 10th percentile. Physical examination shows fair hair and skin, blue eyes, an eczematous rash, and mild dehydration. His urine has a musty odor. Which of the following is the most appropriate diagnostic test for this patient's condition?

Question

A 5-month-old boy is brought to the emergency department with a 2-day history of projectile vomiting, diarrhea, and an episode of generalized tonic-clonic seizure activity just prior to arrival.  He has been exclusively formula-fed since birth.  He was born at 39 weeks gestation and had a "natural birth" at home.  The pregnancy and delivery were uncomplicated.  The boy did not undergo newborn screening due to parental preferences.  His parents and 4-year-old sister are all healthy.  One of his maternal uncles is intellectually disabled and lives in a long-term care facility.  The boy's weight, height, and head circumference are at the 10th percentile.  Physical examination shows fair hair and skin, blue eyes, an eczematous rash, and mild dehydration.  His urine has a musty odor.  Which of the following is the most appropriate diagnostic test for this patient's condition?

Quizplus · Accepted Answer

11ec25c8_d663_94c1_bc81_c9560fc9f1b5_MD0003_00 The clinical signs and family history of this patient are very suggestive of phenylketonuria (PKU). PKU is a rare (1/10,000 births) autosomal recessive disorder that is potentially devastating. A deficiency in the phenylalanine hydroxylase results in an inability to metabolize phenylalanine into tyrosine, which in turn causes an accumulation of phenylalanine and its neurotoxic byproducts. Untreated patients have severe intellectual disability and seizures. Other classic features include fair complexion and musty ("mousy") body odor, as in this patient. Newborn screening is extremely important as early diagnosis and treatment can allow these patients to live relatively healthy lives with normal intellect. Most infants with PKU are asymptomatic initially; diagnosis is typically made from positive newborn screening tests. Tandem mass spectrometry of dried blood spots can detect the presence of metabolic products of phenylalanine. Mass spectrometry screening for PKU is mandated in all 50 states and is the most cost-effective screening test. If PKU is suspected later in life, as in this patient, quantitative amino acid analysis will show elevated phenylalanine levels. Phenylalanine is an essential amino acid, and small amounts are necessary for growth and development. Treatment consists of a low-phenylalanine diet. Cereals, starches, fruits, vegetables, and phenylalanine-free milk formulas are recommended. High-protein foods should be avoided. Early diagnosis and treatment improve the prognosis, with most treated patients having normal mental development and a normal life span. (Choice A) Aldolase B deficiency causes hereditary fructose intolerance. The introduction of fruits and vegetables into the diet is followed by the accumulation of fructose-1-phosphate. Affected infants can present with vomiting, poor feeding, and lethargy. Seizures or encephalopathy follow if fructose is not removed from the diet. This infant is exclusively formula-fed, and hereditary fructose intolerance is therefore unlikely to be the cause of his symptoms. (Choice B) Complete absence of galactose-1-phosphate uridyl transferase activity in red blood cells is consistent with galactosemia. Galactosemia usually presents in the first few days after birth with jaundice, hepatomegaly, and failure to thrive after consumption of breast milk or regular infant formula. (Choice C) A karyotype can diagnose numerical (eg, Down syndrome, Turner syndrome) or large structural (eg, Fragile X syndrome) chromosomal abnormalities. A karyotype is a low-yield test for infants with no dysmorphic features. (Choice E) Failure to thrive and poor feeding are consistent with hypothyroidism. However, seizures and vomiting are not. Elevated thyroid-stimulating hormone levels are found in congenital hypothyroidism, which usually presents with large fontanelles, failure to thrive, and hypotonia. Educational objective: Phenylketonuria is caused by a deficiency of phenylalanine hydroxylase, which results in the buildup of phenylalanine and its neurotoxic metabolites. Clinical features include intellectual disability, fair complexion, eczema, and a musty or "mousy" body odor. Infants diagnosed early through newborn screening and treated with low-phenylalanine diets can expect normal health and development. References: Phenylalanine hydroxylase deficiency: diagnosis and management guideline. (http://www.ncbi.nlm.nih.gov/pubmed/24385074) Universal screening for inherited metabolic diseases in the neonate (and the fetus). (http://www.ncbi.nlm.nih.gov/pubmed/23025760)

A 5-Month-Old Boy Is Brought to the Emergency Department with a 2-Day