Diagnosis, treatment and outcome of glutaric aciduria type I in Zhejiang Province, China

Abstract

SummaryBackgroundGlutaric aciduria type I (GA I; MIM 231670) is a rare autosomal recessive disorder resulting from glutaryl-CoA dehydrogenase deficiency. This article reports our experience in the diagnosis, treatment and outcome of GA I patients in Zhejiang Province, China.Material/MethodsA total of 129,415 newborns (accounting for approximately one-tenth of the annual births in Zhejiang Province) and 9640 high-risk infants were screened for inborn errors of metabolism in the Neonatal Screening Center of Zhejiang Province during a 3-year period. Tandem mass spectrometry and gas chromatography-mass spectrometry were used for diagnosis of the patients. Dietary modification, carnitine supplementation and aggressive treatment of intercurrent illnesses were adapted for GA I patients.ResultsThree infants were diagnosed with GA I by high-risk screening (detection rate: 1/3,213) and 2 were diagnosed by newborn screening (incidence: 1/64,708). Four patients (3 by high-risk screening and 1 by neonatal screening) undergoing MRI examination showed remarkable changes on T2-weighted image. Four patients accepted timely treatment, and in the patient diagnosed by neonatal screening, treatment was delayed until hypotonia appeared 3 months later. Neuropsychological assessment showed mental and motor retardation in 3 patients after treatment, including the patient diagnosed by neonatal screening.ConclusionsIndividualized timely treatment and close monitoring of GA I patients needs to be optimized in China. Appropriate communication with parents may help to achieve successful management of GA I patients.

Impact of newborn screening and quality of therapy on the neurological outcome in glutaric aciduria type 1: a meta-analysis

“…More than 20 years later evidence has increased that early diagnosis and treatment is beneficial. 1,6,15,16,[18][19][20]27,28,[30][31][32][33] This meta-analysis unequivocally confirms that patients identified by NBS show a superior neurologic outcome with a higher rate of normal motor development and a lower rate of acute or insidious onset of MD compared with patients identified by TMS. Accordingly, it is a significant progress that a growing number of countries worldwide (e.g., 17 have meanwhile included GA1 in their national NBS programs or NBS pilot studies 23 and this study will hopefully guide the decision of governments of those countries who have not so far.…”

“…Finally, a total of 15 publications 1,6,15,16,[18][19][20][21][27][28][29][30][31][32][33] reporting on more than one NBS patient were included into quantitative synthesis ( Fig. 1, Table S2) covering 11 populations in nine countries and two multinational publications (with patients from 37 6 and 16 countries, 29 respectively), of which 11 studies 1,6,15,18,20,[27][28][29][31][32][33] also reported on patients identified by TMS (Table S3). Overall, reports on 647 GA1 patients were included in the analysis.…”

“…Two studies reporting on a single patient with acute onset MD and nonadherence to recommended MT each were excluded from the analysis on insidious onset MD. We identified nine studies whose patients followed recommended low lysine diet with supplementation of a lysine-free, tryptophan-reduced, and arginine-fortified AAS according to the guideline, 1,6,15,16,19,20,29,32,33 while patients in another six studies 18,21,27,28,30,31 were treated with a nonrecommended different diet. Two studies compared different forms of MT.…”

“…Two studies compared different forms of MT. 1,33 Nonadherence to MT increases the risk of insidious onset MD…”

Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China

“…The Newborn Screening Center of Zhejiang Province is the largest screening center in China, and initially implemented MS/MS for screening 26 treatable metabolic disorders in symptomatic infants in 2008, and expanded this to newborn screening in 2009. However, MS/MS newborn screening is not currently mandatory, and only 10% of annual births in Zhejiang Province are screened [ 2 ] Samples from symptomatic patients with suspected IEM from throughout the province and neighboring provinces are sent to the Newborn Screening Center of Zhejiang Province. The cost of MS/MS screening in symptomatic infants is 390 RMB (around $59.72).…”