Glutaric acidemia type 1 (GA1) is an autosomal recessive inherited metabolic disorder caused by pathogenic variants in the GCDH gene. The prevalence is approximately 1:150,000 in newborns. The enzyme glutaryl-CoA dehydrogenase is involved in the degradation of the amino acids L-lysine, L-hydroxylysine and L-tryptophan. Decreased enzyme activity leads to accumulation of glutaric acid produced in the metabolic pathway, which cannot be further degraded. Increased levels of glutaric acid (GA), 3-hydroxyglutaric (3-OH-GA), glutaconic acid, and glutarylcarnitine in blood and urine are characteristic. If the disease remains undiagnosed and untreated, an encephalopathic crisis with striatal lesions and severe dystonic-dyskinetic movement disorder will occur in the first 3–36 months. In the absence of a crisis, dystonia gradually develops in children over 6 years of age. Approximately 75% of patients have macrocephaly.
Diagnosis of glutaric acidemia type 1 is part of the newborn screening. If the findings are abnormal, the diagnosis can be confirmed by molecular genetics. With timely initiation of therapy (low lysine diet and carnitine administration), glutaric acidemia type 1 is considered treatable.
Leitlinie 027/018 "Glutarazidurie Typ I, Diagnostik, Therapie und Management", 2016