Two clinical categories: half of the patients
present with an acute neonatal illness with poor feeding, dehydration,
hypothermia, and coma, and if untreated, death secondary to severe metabolic
acidosis, cerebral edema, cerebral hemorrhage, or infection. The other half
of patients either are survivors of the acute neonatal episode or later
developed symptoms and suffer from a chronic intermittent form with similar
episodes. The majority of patients have normal psychomotor development, but
some present with various degrees of developmental delay. The recurrent
episodes often follow upper respiratory infection or intake of protein-rich
food to which patients frequently develop aversion. Most diagnoses of the
disease are made during the first episode. Acute episodes are treated
symptomatically (protein restriction, hydration, correction of acid-base
disturbances, glucose infusion). Along with symptomatic treatment are more
specific therapeutic approaches, such as glycine and carnitine
administration. Under stable conditions of a leucine-restricted diet, the
optimal regimen is 150 mg/kg/day of glycine per os or per nasogastric tube.
During acute crisis, increase glycine supplements to 600 mg/kg/day.
Administration of carnitine with or without glycine also decreases
isovaleric acidemia, but the data are still too limited to evaluate the
optimal combination for long-term management. Chronic pancreatitis may
occur.