A Treatable Neurometabolic Disorder: Glutaric Aciduria Type 1

Glutaric aciduria type 1 (GA-1) is an autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by deficiency of glutaryl-CoA dehydrogenase. It results in the accumulation of 3-hydroxyglutaric and glutaric acid. Affected patients can present with brain atrophy and macrocephaly and with acute dystonia secondary to striatal degeneration in most cases triggered by an intercurrent childhood infection with fever between 6 and 18 months of age. We report two such cases with macrocephaly, typical MRI pictures, and tandem mass spectrometry suggestive of glutaric aciduria type 1. 1. Introduction Glutaric aciduria type I (GA-1) is an autosomal recessive disorder of the degradation of lysine, hydroxylysine, and tryptophan, caused by a defect of the enzyme glutaryl-CoA dehydrogenase [1]. Prevalence of GA-1 is 1 in 56000 [2]. Enzyme deficiency results in an accumulation of glutaric and glutaconic acid, which can be measured by urine testing for organic acids. Glutaric acid has a cytotoxic effect and causes cerebral atrophy and brain damage [3]. It is characterized by macrocephaly at birth or shortly after, dystonia, and many times resembling seizures at the first episode, with degeneration of the caudate and the putamen [4]. Therapy consists in carnitine supplementation to remove glutaric acid, a diet restricted in amino acids capable of producing glutaric acid, and prompt treatment of intercurrent illnesses [5]. Early diagnosis and therapy reduce the risk of acute dystonia in patients with GA-1 [6]. 2. Case Reports 2.1. Case 1 A one-and-half-year-old Muslim male child born of consanguineous marriage presented with gross developmental delay and large head size, with the child having history of recurrent episodes of seizures. Although he could smile responsively and feed well, complete head control had not been achieved. On examination he had macrocephaly (OFC 52？cms, expected 47？cms), broad nasal root, hypertelorism, thin sparse hypopigmented hair, and gross developmental delay. Investigations including peripheral blood picture, serum electrolytes, blood glucose, serum ammonia, and liver function test were normal. Urine for tandem mass spectrometry (TMS) report was suggestive of glutaric aciduria. MRI (on T2 weighted MR) brain reveals frontotemporal atrophy, dilated sylvian fissures with open opercula (bat-wing appearance) with hyperintense lesions in bilateral basal ganglia, and the both frontal white matter and bilateral periventricular area suggestive of glutaric aciduria type 1 (Figure 1). Then the child was put on protein