Experiences during newborn screening for glutaric aciduria type 1: Diagnosis, treatment, genotype, phenotype, and outcomes

Tsai, Fang-Chih; Lee, Han-Jui; Wang, An-Guor; Hsieh, Shu-Chen; Lu, Yung-Hsiu; Lee, Ming-Che; Pai, Ju-Shan; Chu, Tzu-Hung; Yang, Chia‐Feng; Hsu, Ting-Rong; Lai, Chih-Jou; Tsai, Ming-Tzu; Ho, Ping-Hsun; Lin, Min-Chieh; Cheng, Ling-Yee; Chuang, Ya-Chin; Niu, Dau‐Ming

doi:10.1016/j.jcma.2016.07.006

Cited by 31 publications

(25 citation statements)

References 47 publications

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“…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.…”

Section: Study Populationmentioning

confidence: 99%

“…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.…”

Section: Therapeutic Impact On the Neurological Outcomementioning

confidence: 99%

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

Boy

Mengler

Heringer-Seifert

et al. 2021

Genetics in Medicine

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Purpose Glutaric aciduria type 1 (GA1), a rare inherited neurometabolic disorder, results in a complex movement disorder (MD) with predominant dystonia if untreated. Implementation into newborn screening (NBS) programs and adherence to recommended therapy are thought to improve the neurological outcome. Methods Systematic literature search for articles published from 2000 to 2019 was performed using the PRISMA protocol. Studies reporting on more than one individual identified by NBS were included. We investigated effects of interventional and noninterventional variables on neurological outcome. Results Fifteen publications reporting on 647 GA1 patients were included. In the NBS group (n = 261 patients), 195 patients remained asymptomatic (74.7%), while 66 patients (25.3%) developed a MD. Compared with the NBS group, a much higher proportion of patients (349/386; 90.4%; p < 0.0001) diagnosed after the manifestation of neurologic symptoms had a MD and an abnormal motor development (285/349; 81.7%; p < 0.0001). For NBS patients, deviations from the recommended diet increased the risk of insidious onset MD, while delayed start of emergency treatment increased the risk of acute onset MD. Conclusions This meta-analysis demonstrates that NBS programs for GA1 have an overall positive effect on the neurological outcome of affected individuals but their success critically depends on the quality of therapy.

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Section: Study Populationmentioning

confidence: 99%

Section: Therapeutic Impact On the Neurological Outcomementioning

confidence: 99%

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

Boy

Mengler

Heringer-Seifert

et al. 2021

Genetics in Medicine

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Section: Discussionmentioning

confidence: 99%

“…Early GA-I patients are often neglected for their no obvious symptoms before clear diagnosis, consequently, early screening and early diagnosis are important [9] . However, the urine organic acid analysis may appear false negative for the intermittent metabolites discharge in urine, that is, GA-I may not be detected in non-acute phase [9] . In our study, four cases showed increased urinary glutaric acid, 3-hydroxy glutaric acid and glutaryl carnitine, and one case with no special treatment showed no significant abnormality after carrying out GC/MS or MS/MS (at the age of 16.5 years and 18 years), which would be caused by false negative, or age dependent of GA-I.…”

Section: Discussionmentioning

confidence: 99%

Clinical and mutational spectrum of 4 Chinese families with glutaric aciduria type 1

Shi

Shao

Zheng

et al. 2019

Preprint

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Background To investigate clinical presentation and molecular aspects of five patients suffered from glutaric aciduria type I (GA-I ), a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. Methods All five patients were diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Low protein diet supplemented with special formula, GABA analog and L-carnitine were initialed following laboratory confirmation of diagnosis. The clinical and biochemical features were analyzed, and mutational analysis of GCDH was conducted using Sanger sequencing. Results Clinical manifestations of 5 patients varied from macrocephaly to severe encephalopathy, with notably different phenotype between siblings with the same mutations. Three members present complex heterozygous mutations, while two sisters present homozygous mutations. Among them, four mutations in GCDH were identified (c.1133C>T 、c.1244-2A>C 、c.339delT 、c.406G>T). Of these four mutations, c.1244- 2A>C was found in four patients and c.339delT and c.1133C>T has not yet been reported until now. Conclusions In 5 Chinese patients with GA1, two novel mutations of GCDH gene were identified, which may expand the mutation spectrum of GCDH gene. What we found confirm that there is no correlation between clinical phenotype and genotype in GA-I patients, and c.1244-2A>C may be mutation hotspot in Southern China.

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“…, propionic acidemia [PA, OMIM #606054], methylmalonic acidemia [MMA, OMIM #251000], isovaleric acidemia [IVA, OMIM #243500] and glutaric acidemia type 1 [GA1, OMIM # 231670 ] and maple syrup urine disease [MSUD, OMIM #248600]). OAs result from a defect in the branched-chain amino acids (BCAAs) or lysine catabolism [ 28 – 30 ], leading to a specific NBS acylcarnitines pattern [ 31 – 33 ]. MSUD is also due to a defect in the metabolic pathway of the BCAAs [ 20 ], which leads to high levels of BCAAs and alloisoleucine [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Food triggers and inherited metabolic disorders: a challenge to the pediatrician

Maines

Palma

Burlina³

2018

Ital J Pediatr

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Several disorders should be considered in the case of newborns and infants experiencing acute or recurrent symptoms after food ingestion. Immune-mediated adverse food reactions are the most frequent and always to be considered. Nevertheless, in the extensive differential diagnosis, clinicians should also include inherited metabolic disorders (IMDs).This review reports clinical features and diagnostic aspects of the most common IMDs that may present with acute manifestations triggered by food intake. Major focus will be amino acid and protein metabolism defects and carbohydrate disorders.Nowadays, for many of these disorders the risk of an acute presentation triggered by food has been decreased by the introduction of expanded newborn screening (NBS). Nevertheless, clinical suspicion remains essential because some IMDs do not have still reliable markers for NBS and a false negative screening result may occur.The aim of this review is to help pediatricians to take these rare inherited disorders into account in the differential diagnosis of acute or recurrent gastrointestinal symptoms related to food intake, which may avoid delayed diagnosis and potentially life-threatening consequences.

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Experiences during newborn screening for glutaric aciduria type 1: Diagnosis, treatment, genotype, phenotype, and outcomes

Abstract: Early diagnosis by newborn screening followed by full compliance with treatment guidelines is important to a good outcome.

Cited by 31 publications

References 47 publications

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

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

Clinical and mutational spectrum of 4 Chinese families with glutaric aciduria type 1

Food triggers and inherited metabolic disorders: a challenge to the pediatrician

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