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Clinical and genetic features of patients with glutaric aciduria type I (GA1)

      Introduction: GA1 is a metabolic disorder produced by a defect on glutaryl CoA dehydrogenase (GCDH) enzyme, in the GCDH gene localized in 19p13.2 chromosome.
      Objective: To analyze clinical manifestations, neurologic evolution, imaging characteristics and type of mutations found in children with diagnosis controlled in our service.
      Materials and method: Retrospective-descriptive study and prospective analysis of 11 children diagnosed in our center in the last 17 years, with positive genetic studies.
      Results: Of a total of 11 patients, six were male. Eight debuted with anencephalitis-like episode at a mean age of 9,9 months. The three remaining patients debuted with psychomotor delay (mean age 4 months) with two of them presenting an encephalitis-like crisis later. Three patients progressed with macrocephaly. One patient presented mild, two moderate and eight severe disability. Cerebral RM in acute episode showed basal ganglia and white matter compromise, bifrontotemporal atrophy, progressing to striatal atrophy. Residual enzymatic activity was deficient in four patients who were studied. Mutations found were heterozygous to R161Q/R402W, Y133H/R161Q, Y133H/R402W, V133/A385V and homozygous to R402W/R402W, A293T/A293T, Y113H/Y113H. No relationship was found between neurologic severity and specific genotype.
      Conclusion: In our series, the most frequent presentation was an encephalitis-like episode. The most invalidating symptoms were extrapyramidal and neuroimages were distinctive. The homozygous and heterozygous mutation in Y113H and R402W are frequent in chilean population, being Y113H exclusive in this population. Thebiochemical genotype and phenotype did not predict clinical course. In conclusion, presymptomatic diagnosis of this affection allows an appropriate management with a favorable evolution.