So far 12 children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (McKusick 24645) have been described (Wysocki and Hfihnel, 1986). We present a new case of this genetic disorder.The boy was born as a second child of healthy unrelated Caucasian parents. Pregnancy and delivery were normal, birth weight 3200 g. He was breast-fed for 6 months and then transferred to a normal diet without any problems.At the age of 18 months, the child was admitted to hospital because of sudden unconsciousness accompanying hypoglycaemia (0.9 mmolL-~). His condition improved rapidly after correction of the blood glucose level.At the age of 28 months, the child had a mild afebrile upper respiratory tract infection, and, two days later, persistent vomiting and diarrhoea appeared. In the hospital he was pale, dehydrated, hypotonic and lethargic. Hypoglycaemia (1.1 mmo! L-a), metabolic acidosis (pH 7.23, pCO 2 3.11 kPa), hyperammonaemia (242/xmol L-a), higher GT, ALT and AST activity (9.05, 4.28 and 1.27 mmol L -~, respectively) and hepatomegaly were found.Thin layer chromatography of urinary organic acids showed a very large unusual spot at the position of methylmalonic acid, but the specific test for this acid was negative. On the gas chromatogram, several organic acids were elevated. They were identified by gas chromatography-mass spectrometry as 3-hydroxyisovaleric, 3-methylglutaric, 3-methylglutaconic and 3-hydroxy-3-methylglutaric acids and the diagnosis of 3-hydroxy-3-methylglutaric aciduria was made.The tolerance of leucine was tested on the fasting child by a n oral load of 65 mg L-leucine per kg body mass; we could not see any elevation of individual leucine metabolites.3-Hydroxy-3-methylglutaryl-CoA lyase activity in skin fibroblasts was found to be less than 0.5% of normal value (Dr Wanders, University Hospital, Amsterdam).The boy is now 3 years old and his psychomotor development is normal. He was recommended to take frequent meals rich in carbohydrates, and some reduction of fat and leucine-rich meals, such as maize, milk and blood products.It was the first case of this disease in the family; his elder sister and the parents have a normal excretory pattern of organic acids (gas chromatography).
