Clinical, Biochemical and Molecular Characterizations of Patients With Glutaric Aciduria Type 1 in Henan Province, China

Abstract Background: Glutaric acidemia type 1 (GA1) is a rare organic acid metabolism disorder resulted from the deficiency of glutaryl-CoA dehydrogenase (GCDH). There are few studies on GA1 in China. This article is designed to investigate the clinical, biochemical and molecular characterizations of patients with GA1 in Henan province, in order to get further understanding of this disease . Results: The incidence of neonatal GA1 in Henan population was 1/172483. All patients had increased glutarylcarnitine (C5DC), glutaric acid (GA) and 3-hydroxyglutaric acid (3-OH-GA) levels. Twenty mutations were discovered in 14 patients. Four of them were novel: c.523G>A (p.G175S), c.1297G>C (p.A433P), c.467G>A (p.G156D) and c.1125T>G (p.C375W). The most common mutation was c.1064G>A (p.R355H), of which the allelic frequency was 17.86% (5/28), following by c.1109T>C (p.L370P), c.648G>A (p.S216S), c.395G>A (p.R132Q) and c.938G>A (p.R313Q), which had the same allelic frequency 7.14% (2/28). 84.6%(11/13) patients displayed abnormal brain MRI findings, of which cerebral dysplasia and arachnid/ependyma cysts(38.5%,5/13) were most commonly. Clinical features varied widely from asymptomatic to severe encephalopathy. Patients diagnosed by newborn screening had better outcome. A strong correlation was discovered among increasing disability in motor, speech and cognitive function. There were statistical significance differences in motor function(p=0.024) and speech function (p=0.008), but no statistical significance difference in cognitive function (p=0.106) between NBS group and non-NBS group. Conclusions: Our study provided comprehensive information about GA1 in Henan population, including morbidity, clinical, biochemical, molecular and outcome features. The novel variants expanded the GCDH variant spectra. This work emphasize that professional management of NBS programs and experienced genetic metabolic disease experts will be very important and urgent.