[P1-151] A Chinese girl with mitochondrial 3-hydroxy-3-methyglutaryl-CoA synthase deficiency and two novel mutations in the HMGCS2 gene
Mitochondrial 3-hydroxy-3-methyglutaryl-CoA synthase deficiency is a rare autosomal recessive disease caused by the mutations of genes related in the ketone synthesis, leads to hypoketotic hypoglycemia, encephalopathy and hepatomegaly. Only few cases have been documented in the world. In this study, a Chinese case was firstly diagnosed. The proband, a previously healthy girl, presented with intermittent vomiting and disturbance of consciousness induced by acute infectious disease from the age of 9 months. She was admitted because of acute encephalopathy. Hepatomegaly, liver dysfunction, metabolic acidosis and hypoketotic hypoglycemia were noticed. Her urine organic acids, blood aminoacids and acylcarnitine profiles were normal. Blood free carnitine was significantly decreased. A compound heterozygous mutation, c.1201C>A (p.E401X) and c.559＋1C>A, were detected on her HMGCS2 gene, supporting the diagnosis of mitochondrial 3-hydroxy-3-methyglutaryl-CoA synthase deficiency. Both of the two mutations were novel. c.1201C>A was from her father, leading to a premature termination codon. c.559+1C>A is a splicing mutation inherited from her mother. Mitochondrial 3-hydroxy-3-methyglutaryl-CoA synthase deficiency is a rare ketogenesis deficiency disease. The diagnosis of the patients is usually difficult, while the prognosis is good in most cases by timely medical intervention. Carbohydrate administration in acute period and avoiding long-lasting fasting in stable stage are keys to improve the outcome at times of lipolytic stress.