Clinical and metabolic profile of glutaric aciduria type 1 from North India: Tertiary centre experience

Abstract

Introduction: Glutaric aciduria type 1 is caused by deficiency of glutaryl-CoA dehydogenase leading to accumulation of glutarylcarnitine in blood and excretion of glutaric acid, 3-hyroxyglutaric acid and glutaconic acid in urine. It can be diagnosed through high risk screening in symptomatic cases. Aim: To know the clinical, biochemical, neuroimaging and outcome profile of Glutaric aciduria type 1 patient diagnosed during testing by Tandem Mass Spectrometry (TMS) and Gas Chromatography and Mass Spectrometry (GCMS). Materials and Methods: It was retrospective record analysis of patients diagnosed with Glutaric aciduria type 1. 2000 patients were screened for various indications like (developmental delay/regression, unexplained seizures, encephalopathy, dystonia, chorea, large head, unexplained sibling death). Screening strategy involved estimation of lactate, ammonia, TMS and GCMS. Neuroimaging was done where it was required. This study was conducted over a period of three years (Jan 2014 to Dec 2016). Results: Study group comprised of 10 males and 3 females. Median age (interquartile range) of presentation in study group was 11 months (10-22.5). Pretesting diagnosis was suspected as inborn error of metabolism in each case based on clinical presentation. Seizure and dystonia were important clinical presentation. Frontotemporal atrophy was important neuroimaging finding. Macrocephaly was present in two of thirteen cases. Glutarylcarnitine level was normal in 5 of 11 patients, suggesting poor sensitivity of TMS in diagnosed cases. There was wide variation in excretion of urinary metabolite from cases to cases, highlighting genetic heterogenousity. Conclusion: Seizures and dystonia were important clinical presentations. Presence of bilateral frontotemporal atrophy in clinical testing was an important clue to diagnosis. Presence of macrocephaly (important sign of disease) was present in only two cases. There was only one death in follow up. © 2017, Journal of Clinical and Diagnostic Research. All rights reserved.