NMR-based urinalysis for beta-ketothiolase deficiency.

Abstract

BACKGROUND:

Beta-ketothiolase deficiency is a rare inborn errors of metabolism (IEM) affecting the catabolism of isoleucine, characterized by severe ketoacidosis in children of 6 to 24months old. A prompt diagnosis is of paramount importance as the metabolic decompensation can be effectively reverted by glucose infusion and health outcomes are improved on a protein-restricted diet. Currently, majority of the laboratory diagnosis were made based on mass-spectrometry and molecular genetics while little is mentioned on the advancement of nuclear magnetic resonance (NMR) spectroscopy for the diagnosis of this condition.

CASE:

We report a case of beta-ketothiolase deficiency in a 1-y-old Chinese boy who presented with repeated vomiting, impaired consciousness and severe ketoacidosis. NMR urinalysis detected excessive amount of butanone (a disease specific marker of beta-ketothiolase deficiency), tiglylglycine, (intermediate of isoleucine catabolism) and ketones. Diagnosis of beta-ketothiolase deficiency was further established by molecular genetic studies of ACAT1 gene of the proband.

CONCLUSIONS:

This case illustrated that NMR-based urinalysis is complementary to organic acid analysis for diagnosis of beta-ketothiolase deficiency. The operation of NMR is simple and fast; sample preparation is a two-step procedure while the NMR acquisition is automatic and usually takes <15min. We envisage that NMR analysis will become more available in clinical laboratories and will play an important role in acute pediatric care.

• Authors: Chun-Yiu Law, Ching-Wan Lam, Chor-kwan Ching, Kin-Cheong Eric Yau, Tsz-wai Ho, Chi-kong Lai, Chloe Miu Mak
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 438 Pg. 222-5 (Jan 01 2015) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 25195009 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Butanones
• Ketones
• tiglylglycine
• Acetyl-CoA C-Acyltransferase
• Glycine

Topics

• Acetyl-CoA C-Acyltransferase (deficiency, urine)
• Amino Acid Metabolism, Inborn Errors (diagnosis, urine)
• Biomarkers (urine)
• Butanones (urine)
• Gas Chromatography-Mass Spectrometry
• Glycine (analogs & derivatives, urine)
• Humans
• Infant
• Ketones (urine)
• Magnetic Resonance Imaging (methods)
• Male
• Urinalysis (methods)