Early detection of glutaric aciduria type I by newborn screening in Taiwan
Journal
Journal of the Formosan Medical Association
Journal Volume
107
Journal Issue
2
Pages
139-144
Date Issued
2008
Author(s)
Abstract
Background/Purpose: Glutaric aciduria type 1 (GA1) is an inborn error of lysine and tryptophan metabolism. There is a lack of initial diagnostic signs of the disease, but late treatment often results in severe neurologic impairment. In this study, we analyzed the results of screening for GAI in a Chinese population. Methods: Dry blood spots were obtained at about 3 days of age from 357,307 newborns and tested for elevation of glutaryl (C5DC)-carnitine by tandem mass spectroscopy. A second sample of blood spots was required from those cases with abnormal elevation of C5DC-carnitine (higher than the cut-off value) (recall). If the results remained abnormal, those cases were referred for confirmation of the diagnosis and treatment. Results: Between August 2001 and February 2005, there were 40 cases with C5DC-carnitine more than 0.13 μM (the cut-off value), from whom a second sample of blood spots was obtained (recall rate, 0.02%); two cases were confirmed to be affected by GAL Because of the low positive prediction rate using this cut-off value, we elevated the cut-off value slightly. Between February 2005 and August 2006, there were eight cases with C5DC-carnitine more than 0.22 μM from whom a second sample of blood spots was obtained (recall rate, 0.01%); three cases were confirmed to be affected by GA1. All five cases with persistent elevation of C5DC-carnitine were referred and diagnosis was confirmed in each, giving an incidence of 1 in 71,461 newborns. There were no false negatives. Magnetic resonance imaging studies obtained from four cases showed frontotemporal atrophy at the time of diagnosis. Two cases were followed for over 1 year, and under treatment with dietary control and carnitine supplementation, both had normal development and neither exhibited a frank episode of encephalopathic crisis. Conclusion: With properly established cut-offs, GAI can be successfully screened for in populations with a low incidence of the disease. Early treatment is likely to improve the outcome of cases discovered by screening. ? 2008 Elsevier & Formosan Medical Association.
SDGs
Other Subjects
carnitine; glutaryl coenzyme A dehydrogenase; vitamin; aciduria; article; blood analysis; brain atrophy; case report; Chinese; diagnostic accuracy; diagnostic value; diet therapy; early diagnosis; false negative result; follow up; frontal lobe; glutaric aciduria type 1; human; incidence; metabolic encephalopathy; mutational analysis; neuroimaging; newborn; newborn screening; nuclear magnetic resonance imaging; nucleotide sequence; patient referral; prediction; prognosis; reference value; Taiwan; tandem mass spectrometry; temporal lobe; treatment planning
Publisher
Scientific Communications International Ltd
Type
journal article