Expanding phenotypic and mutational spectra of mitochondrial HMG-CoA synthase deficiency.

Expanding phenotypic and mutational spectra of mitochondrial HMG-CoA synthase deficiency. Eur J Med Genet. 2020 Oct 09;:104086 Authors: Rojnueangnit K, Maneechai P, Thaweekul P, Piriyanon P, Khositseth S, Ittiwut C, Chetruengchai W, Kamolvisit W, Theerapanon T, Suphapeetiporn K, Porntaveetus T, Shotelersuk V Abstract Mitochondrial 3-hydroxy-3 methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) is a rare autosomal recessive inborn error of hepatic ketogenesis, caused by mutations in HMGCS2. As its clinical and laboratory manifestations resemble many other metabolic disorders, HMGCS2D definite diagnosis presents a challenge, frequently requiring molecular tests. Only 26 patients with HMGCS2 mutations have been previously described, and this study reports the first two unrelated Thai patients, a 9-month-old male and an 8-month-old female, with HMGCS2D. During acute episodes, steatorrhea and dyslipidemia occurred, both previously unreported. Increased serum levels of triglycerides, very low density lipoproteins (VLDL), and low density lipoproteins (LDL), along with a decreased serum level of HDL were found. Both patients had hypophosphatemic encephalopathy, and the female had metabolic acidosis without hypoglycemia. Trio whole-exome sequencing (WES) revealed that the male harbored two HMGCS2 mutations, a novel c.1480C>T (p.Arg494*) and a previously reported c.1502G>C (p.Arg501Pro), while the female was compound heterozygous for the ...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research