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Glutaric acid was elevated in plasma (0.1-0.6 mg %;normal = undetected), urine (5 gm/gm creatinine;normal=undetected),and CSF (0.25 mg %;normal=undetected) of two siblings, a 1½ year old girl and a 7½ year old boy. Both have a neurodegenerative disorder characterized by initial normalcy followed by progressive deterioration to opisthotonus and posturing. Recurrent metabolic acidemia was present in the male. One sibling has neither glutaric acidemia nor neurologic dysfunction, and the parents deny consanguinity. Glutaryl-CoA is an intermediate in the metabolism of L-lysine, L-tryptophan, and hydroxy-L-lysine, being further metabolized through glutaconyl-CoA to crotonyl-CoA. Oral administration of L-lysine augmented the glutaric aciduria; L-valine did not. Decreasing protein intake from 4.1 to 1.6 gm/kg/day decreased glutaric acid excretion from 5 to 2 gm/gm creat. The metabolism of glutaric acid-l,5-14C in peripheral leucocytes and cultured fibroblasts was normal. If inherited, transmission may be as an autosomal recessive trait; carriers cannot be differentiated easily from controls by lysine loading. It is speculated that (1) the disorder is due to a block at the level of glutaryl-CoA dehydrogenase, and (2) that CNS dysfunction may relate to inhibition by glutaric acid of transport or metabolism of glutamic acid.

Background Glutaric aciduria type I (GA-I) is a rare metabolic disorder caused by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for GA-I. So far only limited data is available enabling health care decision makers to evaluate whether investing into GA-I screening represents value for money. The aim of our study was therefore to assess the cost-effectiveness of newborn screening for GA-I by tandem mass spectrometry (MS/MS) compared to a scenario where GA-I is not included in the MS/MS screening panel. Methods We assessed the cost-effectiveness of newborn screening for GA-I against the alternative of not including GA-I in MS/MS screening. A Markov model was developed simulating the clinical course of screened and unscreened newborns within different time horizons of 20 and 70 years. Monte Carlo simulation based probabilistic sensitivity analysis was used to determine the probability of GA-I screening representing a cost-effective therapeutic strategy. Results Within a 20 year time horizon, GA-I screening averts approximately 3.7 DALYs (95% CI 2.9 – 4.5) and about one life year is gained (95% CI 0.7 – 1.4) per 100,000 neonates screened initially . Moreover, the screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176 Euro) per 100,000 screened neonates over a 20 year time horizon. Conclusion Within the limitations of the present study, extending pre-existing MS/MS newborn screening programmes by GA-I represents a highly cost-effective diagnostic strategy when assessed under conditions comparable to the German health care system.