title: 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.
  
  
  METHODS
  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.affiliation: Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Chun-Yiu
authors.initials: CY
authors.lastname: Law
authors.affiliation: Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk.
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Chor-kwan
authors.initials: CK
authors.lastname: Ching
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Kin-Cheong Eric
authors.initials: KC
authors.lastname: Yau
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Tsz-wai
authors.initials: TW
authors.lastname: Ho
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Chi-kong
authors.initials: CK
authors.lastname: Lai
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Chloe Miu
authors.initials: CM
authors.lastname: Mak
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency* / Q000652:urine; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D002074:Butanones / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D007223:Infant; D007659:Ketones / Q000652:urine; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D016482:Urinalysis / Q000379:methods*
chemical_list: D015415:Biomarkers; D002074:Butanones; D007659:Ketones; C003603:tiglylglycine; D000102:Acetyl-CoA C-Acyltransferase; D005998:Glycine
keywords: Beta-ketothiolase deficiency; Inborn errors of metabolism; NMR spectroscopy