Metabolic encephalopathy in beta-ketothiolase deficiency: the first report from India

Brain Dev. 2014 Jun;36(6):537-40. doi: 10.1016/j.braindev.2013.07.007. Epub 2013 Aug 16.

Abstract

Beta-ketothiolase deficiency, or mitochondrial acetoacetyl-CoA thiolase (T2) deficiency, is a rare autosomal recessive disorder affecting isoleucine catabolism and ketone body metabolism. A patient from South India presented with acute ketoacidosis at 11 months of age. During the acute crisis the C5OH (2-methyl-3-hydroxybutyryl) carnitine and C5:1 (tiglyl) carnitine were elevated and large amounts of 2-methyl-3-hydroxybutyrate, tiglylglycine, and 2-methylacetoacetate were excreted. Brain CT showed bilateral basal ganglia lesions. Potassium ion-activated acetoacetyl-CoA thiolase activity was deficient in the patient's fibroblasts. The patient is a homozygote for a novel c.578T>G (M193R) mutation. This is the first report of T2 deficiency confirmed by enzyme and molecular analysis from India.

Keywords: 2-Methyl-3-hydroxybutyrate; ACAT1; C5OH; Ketoacidosis; T2 deficiency; Tiglylglycine.

Publication types

  • Case Reports

MeSH terms

  • Acetyl-CoA C-Acetyltransferase / genetics
  • Acetyl-CoA C-Acetyltransferase / metabolism
  • Acetyl-CoA C-Acyltransferase / deficiency*
  • Acetyl-CoA C-Acyltransferase / genetics
  • Acetyl-CoA C-Acyltransferase / metabolism
  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Amino Acid Metabolism, Inborn Errors / diagnostic imaging*
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Brain / diagnostic imaging
  • Brain Diseases, Metabolic / diagnosis
  • Brain Diseases, Metabolic / diagnostic imaging*
  • Brain Diseases, Metabolic / genetics*
  • Brain Diseases, Metabolic / metabolism
  • DNA Mutational Analysis
  • Humans
  • India
  • Infant
  • Male
  • Mutation
  • Tomography, X-Ray Computed

Substances

  • Acetyl-CoA C-Acyltransferase
  • ACAT1 protein, human
  • Acetyl-CoA C-Acetyltransferase

Supplementary concepts

  • Beta ketothiolase deficiency