Glutaric aciduria type I: Outcome in the Republic of Ireland

Abstract

Twenty-one patients have been diagnosed with glutaric aciduria type I over a 16-year period in the Republic of Ireland, 11 following clinical presentation and 10 following a high-risk screen. Nineteen have been managed with diet. Eight patients have died, of whom 7 were diagnosed clinically. Six had dystonic and one spastic cerebral palsy. Of the 11 patients who did not have cerebral palsy, 10 were diagnosed following a high-risk screen. Seven of the 11 have no abnormal neurological signs; 6 of the 7 have abnormal CT or MRI findings; and no case of striatal degeneration has occurred during the past 14 years in the high-risk screened group.

Natural History, Outcome, and Treatment Efficacy in Children and Adults with Glutaryl-CoA Dehydrogenase Deficiency

“…In addition, the age at first crisis and severity of the clinical presentation was also not significantly influenced by the biochemical phenotype. In contrast to this, the outcome (3,20,25). *Ireland (asymptomatic/symptomatic patients: 10/11); **the Amish Community (20/17); and ***Scandinavia (3/25).…”

“…Before the onset of an encephalopathic crisis, the presentation of affected children is nonspecific, with macrocephaly being the most characteristic clinical feature (3,19,21). If diagnosed in a timely manner and treated with a special diet and L-carnitine supplementation as well as an intensified emergency therapy during intercurrent illness (24), the development of acute encephalopathic crises and striatal damage has been prevented in 65-95% of children (3,19,25). However, the neuroprotective effect of different protocols has not been studied systematically and the level of evidence in the majority of clinical studies has been low.…”

“…Furthermore, it remains to be elucidated whether treatment efficacy varies among specific subgroups of patients, such as insidious-or late-onset type. We could not estimate the neuroprotective value of emergency treatment, which is considered an important treatment strategy in GCDH deficiency (3,19,25) because the exact timing of the start of treatment could not be ascertained in the retrospective analysis of the episodes of acute illness.…”

Decline of Acute Encephalopathic Crises in Children with Glutaryl-CoA Dehydrogenase Deficiency Identified by Newborn Screening in Germany

“…In two variant forms of GCDH deficiency (insidious onset, late onset), neurologic disease develops without overt crises, suggesting chronic neurodegenerative changes. If treatment starts before the onset of irreversible neurologic symptoms, encephalopathic crises can be prevented in the majority of patients (4,8,(11)(12)(13).…”

“…However, the natural history of patients with GCDH deficiency does not correlate with the genotype or the biochemical phenotype (32) resulting in a similar a priori risk for all untreated patients to suffer acute encephalopathic crises (4,10,11,13). Furthermore, no variables are known that allow predicting the disease course of presymptomatically diagnosed patients and the necessity for treatment.…”