2-Methylglutaconic acid as a biomarker in routine urine organic acids leading to the diagnosis of glutaric acidemia type I in a low excretor.

Autor: Wongkittichote P; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Hong X; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Master SR; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Kaur S; Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ, USA., Cuddapah SR; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., He M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: HeM@chop.edu.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2023 Apr; Vol. 138 (4), pp. 107549. Date of Electronic Publication: 2023 Feb 23.
DOI: 10.1016/j.ymgme.2023.107549
Abstrakt: GA1 (OMIM# 231670) is an organic aciduria caused by defective Glutaryl-CoA dehydrogenase (GCDH), encoded by GCDH. Early detection of GA1 is crucial to prevent patients from developing acute encephalopathic crisis and subsequent neurologic sequelae. Diagnosis of GA1 relies on elevated glutarylcarnitine (C5DC) in plasma acylcarnitine analysis and hyperexcretion of glutaric acid (GA) and 3-hydroxyglutaric acid (3HG) in urine organic acid (UOA) analysis. Low excretors (LE), however, exhibit subtly elevated or even normal plasma C5DC and urinary GA levels, leading to screening and diagnostic challenges. The measurement of 3HG in UOA is thus often used as the 1st tier test for GA1. We described a case of LE detected via newborn screen with normal excretion of GA, absent of 3HG and increased 2-methylglutaconic acid (2MGA), which was detected at 3 mg/g creatinine (reference interval <1 mg/g creatinine) without appreciable ketones. We retrospectively examined UOA of 8 other GA1 patients and the 2MGA level ranged from 2.5 to 27.39 mg/g creatinine, which is significantly higher than normal controls (0.05-1.61 mg/g creatinine). Although the underlying mechanism of 2MGA formation in GA1 is unclear, our study suggests 2MGA is a biomarker for GA1 and should be monitored by routine UOA to evaluate its diagnostic and prognostic value.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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