Glutaric aciduria type I: outcome following detection by newborn screening

Abstract

Glutaric aciduria type I (GA I), a cerebral organic acidaemia with the potential for severe neurological consequences, can now be detected by tandem mass spectrometry newborn screening. Early detection with implementation of careful management strategies appears to lessen the likelihood of neurological damage. We assessed the outcome in all 10 GA I patients detected in New South Wales during the last decade. Three patients were detected clinically and 7 by newborn screening. Diagnosis was confirmed by detection of significantly elevated urinary 3-hydroxybutyrate and glutarate in urine, isolated elevation of glutarylcarnitine in plasma, typical clinical and MRI findings in several, and mutation analysis or enzyme analysis on cultured skin fibroblasts in 4 cases. The birth frequency was 1:90 000. Following diagnosis, treatment was initiated in all children with oral carnitine (100 mg/kg per day) and a low-protein diet supplemented with a lysine-free, low-tryptophan amino acid formula. Disability was assessed in fields of motor, cognitive and speech development and scored according to Kyllerman. Clinically diagnosed patients were all symptomatic, with severity scores (out of 9) of 3, 5 and 9. Six of seven patients detected by newborn screening are asymptomatic, 4 being aged 2–6 years. One patient had a severe decompensation at 7 months, despite full management advice and treatment, and later died. Our data support previous findings that early diagnosis reduces neurological complications, but show that even with early diagnosis and careful management severe complications may ensue in some.