Cinical treatment of 3-hydroxy-3-methylglutaric aciduria and a novel mutation on 3-hydroxy-3-methylglutaryl-coenzyme A lyase gene

Objective To investigate the clinical manifestations and biochemical characteristics of 3-hydroxy-3-methylglutaric aciduria, and discuss results of 3-hydroxy-3-methylglutaryl-coenzyme A lyase (HMGCL) gene mutation. Methods The clinical data of a boy with 3-hydroxy-3-methylglutaric aciduria who was treated at Peking University First Hospital on December 7th 2014 was collected into this study. The admission examination, auxiliary examination, diagnosis and treatment, gene detection and follow-up of this boy were retrospectively analyzed. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Peking University First Hospital. Informed consents were obtained from patient's parents. Results The boy complained of unexplained diarrhea, vomiting, repeated hematemesis, fever 2 d and coma 3 h. The admission examination and auxiliary examination results showed increased white blood cell count, liver damage, electrolyte imbalance, low blood sugar, blood clotting abnormalities, low-protein, high ammonia, metabolic acidosis. Cranial MRI result showed that abnormal signal could be found in bilateral lateral ventricle and double fronto-temporal parietal cortex. The final diagnosis of the boy was 3-hydroxy-3-methylglutaric aciduria. By limiting protein intake, intravenous infusion of glucose and L-carnitine treatment, the symptom alleviated gradually. Genetic analysis results showed that exon region of HMGCL was found two heterozygous mutation point: c. 509G> T and c. 348 + 1 G>C, where c. 509G> T was heterozygous mutation from the mother, c. 348 + 1 G>C emerged in child homozygous mutation, the mutation site of c. 348+ 1G>C splice site mutation caused amino acid changes p. Cys170Phe, splicing (cysteine phenylalanine, shear mutation). After discharge, the six months follow-up results showed as follow. Psychomotor developed slightly behind the health children, but no significant setback. The boy lived in good general condition, and biochemical markers and the level of urinary 3-hydroxy-3-methylpentyl reduce to normal range. Conclusions 3-hydroxy-3-methylglutaric aciduria is one of rare autosomal recessive genetic disease. Genetic gene detection and genetic analysis of HMGCL was helpful not only to diagnose the disease, but also crucial important to genetic counseling for family guidance and prenatal diagnosis. Key words: 3-Hydroxy-3-methylglutaric aciduria; 3-Hydroxy-3-methylglutaryl-coenzyme A lyase gene; Organic acid; Metabolic diseases; Child