3‐Hydroxy‐3‐methylglutaryl‐CoA‐lyase deficiency

Abstract

A 1-year-old Austrian girl of healthy non-consanguineous parents was admitted ~o hospital because of vomiting and diarrhoea. During infancy vomiting and feeding difficulties were reported repeatedly. Nutrition consisted unusually in a mixture of one-third milk and two-thirds water. Shortly before admission change to whole milk had taken place.The liver was enlarged, consciousness was reduced. There was acidosis (pH 7.32), some ketosis and hypoglycaemia (50 mg/dl). Transaminases were elevated. The organic acids in urine showed, in addition to dicarboxylic aciduria (glutaric acid 0.06, adipic acid 0.60, suberic acid 0.11 and sebacic acid 0.04mmol/mmol creatinine), the typical pattern for 3-hydroxy-3-methylglutaric aciduria (3-hydroxy-3-methylglutaric acid 8.12, 3-methylgtutaconic acid 3.26, 3-methylglutaric acid 0.40 and 3-hydroxyisovaleric acid 2.12 mmol/mmol creatinine) due to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (McKusick 24645).After protein reduction the abnormal organic acids decreased but did not completely disappear in the following months. While hepatomegaly disappeared 3 weeks after admission, transaminases normalized after the next 2months. The activity of 3-hydroxy-3-methylglutaryl-CoA lyase (Sovik et al., 1984) was reduced to 0.07nmolmin -1 (mg protein) -~ in the patient's fibroblasts, only 1.5% of mean controk An oral glucose tolerance test showed the following glucose values: 0min, 77; 30rain, 113.9; 60min, 91.6; 120min, 74.8 and 180min, 96mg/dl, and the following insulin values: 0min, 13.4; 30min, 20.1; 60min, 18.0; 120min, 9.0 and 180min, 13.0~tU/ml. About 3weeks after admission not only a protein-(1.5 g kg -1 day -1) and fat-(1.4 g kg-1 day-i) restricted diet, but also carnitine supplement was introduced. With approximately 100mgkg -t day -1 there was no carnitine deficiency (total carnitine in plasma 77, free carnitine 39~mol/L, creatinine 47~tmol/L; total carnitine in urine 4900~tmol/L, free carnitine 2900/xmol/L, creatinine 6560/zmol/L). The mother changed the regime on her own and discontinued the carnitine supplementation for 2 months.With the exception of severe hypoglycaemic seizures on one morning (blood glucose 18 mg/dl) the 2-year-old child shows a normal development.