Hyperphenylalalinemia due to dihydropteridine reductase deficiency
Overview
A genetic condition where phenylalanine (component of protein) is unable to be broken down due to an enzyme (phenylalanine hydroxylase) deficiency which leads to a harmful build up of the compound. The condition is characterized by neurological symptoms as well as the presence of increased levels of phenylalanine in the blood.
Symptoms
* Progressive neurological symptoms * Basal ganglia calcifications * Subcortical calcifications * Increased blood phenylalanine * Phenylketonuria
Causes
PKU is transmitted by an autosomal recessive gene on chromosome 12. Patients with this disorder have insufficient hepatic phenylalanine hydroxylase, an enzyme that acts as a catalyst in the conversion of phenylalanine to tyrosine. As a result, phenylalanine and its metabolites accumulate in the blood, eventually causing mental retardation if left untreated. The exact biochemical mechanism that causes this retardation is unclear. In the United States, this disorder occurs in 1 in approximately 14,000 births. (About 1 person in 60 is an asymptomatic carrier.) The gene is most common in Ireland, Scotland, Belgium, and West Germany and rare in Blacks, Asians, Native Americans, Finns, and Ashkenazi Jews.
Treatment
Treatment consists of restricting dietary intake of the amino acid phenylalanine to keep phenylalanine blood levels between 3 and 9 mg/dl. Because most natural proteins contain 5% phenylalanine, they must be limited in the child's diet. An enzymatic hydrolysate of casein, such as Lofenalac powder or Pregestimil powder, is substituted for milk in the diets of affected infants. This milk substitute contains a minimal amount of phenylalanine, normal amounts of other amino acids, and added amounts of carbohydrate and fat. Dietary restrictions usually continue throughout life. The special diet for PKU calls for careful monitoring. Because the body doesn't make phenylalanine, overzealous dietary restriction can induce phenylalanine deficiency, producing lethargy, anorexia, anemia, rashes, and diarrhea.