Mutation analysis of Indian patients with urea cycle defects

Gupta, Neerja; Kabra, Madhulika; Häberle, Johannes

doi:10.1007/s13312-012-0100-y

Cited by 9 publications

(8 citation statements)

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“…An accurate genetic diagnosis is essential not only for appropriate management of the child, but also for genetic counseling in the context of subsequent pregnancies and carrier testing. So far, only a few mutations have been reported from India [ 9 – 12 ]. The Indian population is a unique mix of several cultures and sects, with considerable consanguinity.…”

Section: Introductionmentioning

confidence: 99%

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Bijarnia-Mahay

Häberle

Jalan

et al. 2018

Orphanet J Rare Dis

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BackgroundUrea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile.ResultsWe present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed.Molecular genetic analysis revealed two common ASS1 mutations: c.470G > A (p.Arg157His) and c.1168G > A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis.ConclusionsWe report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0908-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Bijarnia-Mahay

Häberle

Jalan

et al. 2018

Orphanet J Rare Dis

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“…Urea cycle disorders (UCD) occur when a body fails to metabolize the surplus nitrogen produced by the breakdown of protein and other nitrogen containing molecules. Gupta, Kabra and Haberle [ 5 ] reported four cases of UCD in which all showed ammonia accumulation with a varying severity of enzyme defects in the urea cycle. In three out of the four cases, sodium benzoate therapy was given but this did not bring significant improvements.…”

Section: Resultsmentioning

confidence: 99%

“…The International League Against Epilepsy (ILAE) recognizes eight types of metabolic epilepsies, namely: biotinidase and holocarboxylase synthase deficiency, cerebral folate deficiency, creatine disorders, folinic acid responsive seizures, glucose transporter type 1 (GLUT-1) deficiency, mitochondrial disorders, peroxisomal disorders and pyridoxine-dependent epilepsy (PDE) [ 2 ]. However, we also found evidence for more types of metabolic epilepsies during our literature search, such as: urea cycle disorders [ 5 ], glutaric aciduria [ 6 ], molybdenum cofactor deficiency [ 7 ], non-ketotic hyperglycaemia [ 8 ], non-ketotic hyperglycinemia [ 9 ], and succinic semialdehyde dehydrogenase deficiency [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment, Therapy and Management of Metabolic Epilepsy: A Systematic Review

Lee

Choo

Chung

et al. 2018

IJMS

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Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect. After applying our inclusion and exclusion criteria as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed a total of 43 articles. Based on the reviewed articles, we summarized the methods used for the treatment, therapy and management of metabolic epilepsy. These methods were tailored to address the root causes of the metabolic disturbances rather than targeting the epilepsy phenotype alone. Diet modification and dietary supplementation, alone or in combination with antiepileptic drugs, are used in tackling the different types of metabolic epilepsy. Identification, treatment, therapy and management of the underlying metabolic derangements can improve behavior, cognitive function and reduce seizure frequency and/or severity in patients.

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“…et al [9] have reported genetic diagnosis of three cases of citrullinemia type 1 with antenatal diagnosis in one. The present report is only the second in which genetic diagnosis for citrullinemia is being documented in Indian literature.…”

Section: Discussionmentioning

confidence: 99%

Citrullinemia type 1: Genetic diagnosis and prenatal diagnosis in subsequent pregnancy

et al. 2013

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Citrullinemia type 1 was diagnosed by tandem mass spectrometry in a full term male neonate who presented with an acute catastrophic collapse on the 3rd day of life. Both parents were identified to be carriers for the exon 15 p Gly390Arg mutation in the argininosuccinate synthetase gene located at chromosome 9q34.1. Chorionic villus sampling and prenatal genetic testing in the subsequent pregnancy revealed an affected fetus resulting in termination of pregnancy.

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Mutation analysis of Indian patients with urea cycle defects

Cited by 9 publications

References 1 publication

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Treatment, Therapy and Management of Metabolic Epilepsy: A Systematic Review

Citrullinemia type 1: Genetic diagnosis and prenatal diagnosis in subsequent pregnancy

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