Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or ... Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting (Aledo et al., 2006).
Thompson et al. (1997) described an 11-year-old boy, born of nonconsanguineous Chinese parents, with deficiency of mitochondrial HMG-CoA synthase. The boy first presented at 6 years of age after mild gastroenteritis with poor oral intake for 2 to ... Thompson et al. (1997) described an 11-year-old boy, born of nonconsanguineous Chinese parents, with deficiency of mitochondrial HMG-CoA synthase. The boy first presented at 6 years of age after mild gastroenteritis with poor oral intake for 2 to 3 days that culminated in a brief generalized seizure that left him semicomatose. His blood glucose concentration was 9 mg per deciliter, and a urine dipstick test was negative for ketones. He had previously been well and tolerated minor illnesses without difficulty. He was asymptomatic except during prolonged fasting. Provocative tests were performed when he was 7 years of age. After fasting for 22 hours, the patient had a blood glucose concentration of 41 mg per deciliter and a plasma beta-hydroxybutyrate concentration of 0.2 mmol per liter. He rapidly became comatose and awake about 30 minutes after receiving a bolus intravenous injection of dextrose followed by a continuous infusion at a rate of 10 mg per kilogram per minute. The response was slower than that expected in children with brief episodes of hypoglycemia, in whom coma usually resolves within minutes. After the ingestion of long chain triglycerides, the patient's plasma free fatty acid concentrations increased appropriately, but plasma beta-hydroxybutyrate concentrations remained low. These concentrations also remained low after the ingestion of medium-chain triglycerides, indicating that enzyme function after the oxidation of long chain fatty acids, the first step in ketone body formation, was abnormal. Four hours after the ingestion of medium-chain triglycerides, the boy became comatose, with a blood glucose concentration of 50 mg per deciliter. Bouchard et al. (2001) followed up on this patient and another patient reported by Morris et al. (1998). They noted that both patients had normal development and no further decompensation following diagnosis. Aledo et al. (2001) described a boy with HMG-CoA synthase-2 deficiency who presented at the age of 11 months with acute hypoglycemic coma and respiratory arrest after a 2-day history of gastroenteritis, vomiting, and poor food intake. In addition to low blood glucose, elevated transaminases and lactate dehydrogenase were found at admission. During a monitored fasting test, massive elevation of plasma free fatty acids without concomitant elevation of total plasma ketones was observed. The patient was placed on supplementary carnitine and the family was advised to avoid fasting for more than 8 hours and to administer a caloric drink at around midnight. Under this regimen, there were no subsequent hypoglycemic episodes, and the child at 4 years of age was developing normally with no residual neurologic impairment.
In the patient with mitochondrial HMG-CoA synthase deficiency reported by Thompson et al. (1997), Bouchard et al. (2001) identified homozygosity for a phe174-to-leu (F174L; 600234.0001) mutation in exon 2 of the HMGCS2 gene. In another patient with deficiency ... In the patient with mitochondrial HMG-CoA synthase deficiency reported by Thompson et al. (1997), Bouchard et al. (2001) identified homozygosity for a phe174-to-leu (F174L; 600234.0001) mutation in exon 2 of the HMGCS2 gene. In another patient with deficiency of mitochondrial HMG-CoA synthase who had been described by Morris et al. (1998), Bouchard et al. (2001) found an arg424-to-ter (R424X; 600234.0001) mutation in compound heterozygosity. The second mutation in this patient was not characterized. In a boy with mitochondrial HMG-CoA synthase deficiency, Aledo et al. (2001) identified compound heterozygosity for 2 mutations in the HMGCS2 gene (600234.0003-600234.0004).