The parents of a 3-month-old infant rush their child to the ER following a seizure. Blood work indicates the child is hyperphenylalaninemic with serum phenylalanine measured at 650 μM. The attending physician suspects the infant has PKU and places the infant on a low-phenylalanine diet. Upon follow-up 3-days later, the level of serum phenylalanine is found to be reduced to 250 μM. However, while at home, the infant developed progressive movement disorders, difficulty swallowing, seizures, and elevated body temperature. A defect in which of the following enzymes would best explain the hyperphenylalaninemia and the lack of positive outcome on the low phenylalanine treatment?

Question

Quizplus · Accepted Answer

A defect in dihydropteridine reductase would lead to hyperphenylalaninemia and a lack of response to a low-phenylalanine diet, as this enzyme is necessary for the regeneration of tetrahydrobiopterin, a cofactor for phenylalanine hydroxylase.  Several hyperphenylalaninemias are not PKU and are called non-PKU hyperphenylalaninemias (HPA). Hyperphenylalaninemia is defined as a plasma phenylalanine concentration greater than 120 μM. PKU is characterized by plasma phenylalanine greater than 1000 μM and HPA have plasma phenylalanine amounts that are less than 1000 μM. Dihydropteridine reductase (DHPR) deficiency leads to neurological signs at age 4 or 5 months, although clinical signs are often obvious from birth. The principal symptoms include psychomotor retardation, tonicity disorders, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficult swallowing.

The Parents of a 3-Month-Old Infant Rush Their Child to the ER