Acidemia, Glutaric Type I

Key Features

• Suspect in children with acute basal ganglia necrosis, macrocrania with subdural bleeds, and acute or progressive dystonia

• Presymptomatic diagnosis by newborn screening and treatment reduces the incidence of acute encephalopathic crises

• Caused by deficiency of glutaryl-CoA dehydrogenase

• Patients have frontotemporal atrophy with enlarged sylvian fissures and macrocephaly

• Sudden or chronic neuronal degeneration in the caudate and putamen causes an extrapyramidal movement disorder in childhood with dystonia and athetosis

Clinical Findings

• May present with retinal hemorrhages and intracranial bleeding

• Severely debilitated children often die in the first decade, but many patients have had only mild neurologic abnormalities

• Symptoms almost always develop in the first 6 years of life, which represents the vulnerable period

• The condition is autosomal recessive and prenatal diagnosis is possible

Diagnosis

• Should be suspected in patients with acute or progressive dystonia in the first 6 years of life

• MRI of the brain is highly suggestive

• Diagnosis is supported by finding glutaric, 3-hydroxyglutaric acid, and glutarylcarnitine in urine or serum or by finding two mutations in the GCDH gene

• Demonstration of deficiency of glutaryl-CoA dehydrogenase in fibroblasts can confirm the diagnosis

• Prenatal diagnosis is by mutation analysis, enzyme assay, or quantitative metabolite analysis in amniotic fluid

Treatment

• Strict catabolism prevention during any intercurrent illness is critically important

• Supplementation with large amounts of carnitine and provision of a lysine and tryptophan restricted diet reduces the risk of degeneration of the basal ganglia

• Early diagnosis does not prevent neurologic disease in all patients, but it clearly reduces the risk, warranting newborn screening

• Neurologic symptoms, once present, do not resolve

• Symptomatic treatment of severe dystonia is important for affected patients