The correct answer is E. Population-based newborn screening has enabled health care providers to detect some metabolic disorders in a single process that involves collecting dried blood spot specimens from heel sticks in all newborns. Newborn screening is conducted in all states. Most newborn screening programs currently test for primary congenital hypothyroidism, galactosemia, sickle cell disease, other hemoglobinopathies, and phenylketonuria. Phenylketonuria is caused by a deficiency of phenylalanine hydroxylase, which is normally found in organs outside of the brain. As a result, the normal hydroxylation of phenylalanine to tyrosine does not take place. If not recognized, a normal diet will lead to accumulation of large amounts of phenylalanine. In the brain there is a delay of maturation, defective myelination, and decreased pigmentation of the substantia nigra. Affected children have deficient pigmentation. They are irritable and vomit early on before showing delayed milestones. By 18 months seizures are common.
Hartnup disease (choice A) is not one of the diseases routinely tested in newborn screening. The disease is a combination of intermittent episodes of unsteady gait (ataxia), emotionality, and a photosensitive skin rash in a patient coming from a consanguineous mating. This disease is a recessively inherited error of metabolism characterized by a deficiency in the gastrointestinal and renal transport of tryptophan and certain other monoaminomonocarboxylic amino acids. The critical diagnostic test for Hartnup disease is the demonstration of the pattern of excessive excretion of monoaminomonocarboxylic acids in the urine. The direct selection of this single, simple urine screening test eliminates the need for further laboratory testing.
Homocystinuria (choice B) is not one of the diseases routinely tested for in newborn screening. It is the most common disorder of metabolism of sulfur-containing amino acids. In most cases, cystathionine synthetase is lacking. The enzyme synthesizes the catabolism of cystathionine from homocysteine and serine. As a result, increased levels of homocysteine and methionine accumulate. Patients have strokes in the first year or two of life. Patients who have acquired elevated homocystine levels can have folate deficiency, and folate replacement may be used to help normalize the homocysteine levels. Although elevated homocysteine levels may be associated with increased risk for atherosclerosis, there is no proof that normalizing these levels with folate supplementation changes their cardiovascular risk pattern at this time.
Lesch-Nyhan syndrome (choice C) is not one of the diseases routinely tested for in newborn screening. It is a disorder of purine metabolism caused by a lack of hypoxanthine-guanine phosphoribosyltransferase. This leads to increased purine metabolism with a buildup of uric acid that may simulate gout. The neurologic syndrome that differentiates it from most other disorders is the uniform presence of self-mutilation. Severe dementia, spasticity, and choreoathetosis start in the first year of life.
The oculocerebrorenal syndrome (choice D) is not one of the diseases routinely tested for in newborn screening. The oculocerebrorenal syndrome is a disorder of amino acid transport and is sex-linked recessive. Patients have elevated lysine levels in the urine. The kidney defect is an aminoaciduria with renal tubular acidosis and rickets. Neurologically, there is severe retardation and growth delay.
PEARL: PKU is a rare inborn error of metabolism that is associated with an elevated level of blood phenylalanine. If undetected and untreated, patients can develop mental retardation, problems with executive functioning, and seizures. Newborn screening identifies this deficiency of hepatic phenylalanine hydroxylase activity. Treatment is by restriction of dietary protein and phenylalanine . When dietary regimens are followed, patients are able to develop a normal IQ. Blood testing is drawn via heel stick soon after birth.
