Diagnosis and Management of Gaucher Disease in India – Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics

Puri, Ratna Dua; Kapoor, Seema; Kishnani, Priya S.; Dalal, Ashwin; Gupta, Neerja; Muranjan, Mamta; Phadke, Shubha R.; Anupam, Sachdeva; Verma, Ishwar C.; Mistry, Pramod K.; Force, Gaucher Disease Task

doi:10.1007/s13312-018-1249-9

Cited by 27 publications

(19 citation statements)

References 52 publications

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“…Nearly two-thirds of them were from North India and consanguinity among them was only 10%. Although only one-third of them were from South India, due to the traditional marriage practices [16], 23.3% of them were born of consanguineous marriages. The whole spectrum of non-neuronopathic type (GD1), acute neuronopathic type (GD2), and chronic neuronopathic type (GD3) were seen, although GD2 constituted only 2 (3.3%) of the cohort.…”

Section: Resultsmentioning

confidence: 99%

Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study

Barney

Danda

Abraham

et al. 2021

Public Health Genomics

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Introduction: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder, in which biallelic pathogenic variants in the Glucosidase beta acid (GBA) gene result in defective functioning of glucosylceramidase that causes deposition of glucocerebroside in cells. GD has 3 major types namely, non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). Definite treatment options are limited and expensive. They succumb early to the disease, if untreated. There is paucity of studies from the Indian subcontinent, which elicit the factors resulting in their premature mortality. Materials and Methods: A retrospective study was carried out in a tertiary care setting of South India to assess the clinical profile, mutation spectrum, and various management strategies (only supportive therapy, enzyme replacement therapy [ERT], substrate reduction therapy [SRT] haematopoietic stem cell transplant [HSCT]), and mortality predictors of patients with GD from 2004 to 2019. A Kaplan-Meier survival curve was plotted. In silico predictions were performed for novel variants. Results: There were 60 patients with all types of GD seen over the study period of 15 years. Their median age at diagnosis was 2 years. The median follow-up was for 5 years (interquartile range [IQR] = 2–8). The overall mortality rate was 35%; however, it was only 10% in those receiving definite treatment. Mortality was higher (47.5%) by more than 4 folds in those only on supportive therapy. The median survival from the time of diagnosis was 6.3 years (IQR = 3.5–10.8) in the definite treatment group and 3.5 years (IQR = 1–5) in those on supportive therapy. The Kaplan-Meier survival analysis showed significant (p value 0.001) mortality difference between these groups. The multiple logistic regression analysis found the neuronopathic type (OR = 5) and only supportive therapy (OR = 6.3) to be the independent risk factors for premature mortality. Conclusion: GD is a rare disease with a high mortality rate, if left untreated. ERT and SRT are the definitive treatments which increase the survival. In resource-limited settings like India, with higher prevalence of the neuronopathic type, HSCT may be a more suitable definitive treatment option, due to its one-time intervention and cost, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD needs to be established further by substantial patient numbers undergoing it.

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Section: Resultsmentioning

confidence: 99%

Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study

Barney

Danda

Abraham

et al. 2021

Public Health Genomics

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“…Biallelic variants in the GBA gene causing a de ciency of acid β-glucosidase and cause Gaucher disease, the most common lysosomal storage disorder in the world [75]. The variant p.Gly289Ala and p.Leu483Pro were observed in one individual in the present cohort.…”

Section: Slc26a4 Related Hearing Lossmentioning

confidence: 52%

NGS based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study.

Singh¹,

Bijarnia-Mahay²,

Ramprasad

et al. 2020

Preprint

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Background: To determine the carrier frequency and pathogenic variants of common genetic disorders in the north Indian population by using next generation sequencing (NGS).Methods: After pre-test counselling, 200 unrelated individuals (including 88 couples) were screened for pathogenic variants in 88 genes by NGS technology. The variants were classified as per American College of Medical Genetics criteria. Pathogenic and likely pathogenic variants were subjected to thorough literature-based curation in addition to the regular filters. Variants of unknown significance were not reported. Individuals were counselled explaining the implications of the results, and cascade screening was advised when necessary.Results: Of the 200 participants, 52 (26 %) were found to be carrier of one or more disorders. Twelve individuals were identified to be carriers for congenital deafness, giving a carrier frequency of one in 17 for one of the four genes tested (SLC26A4, GJB2, TMPRSS3 and TMC1 in decreasing order). Nine individuals were observed to be carriers for cystic fibrosis, with a frequency of one in 22. Three individuals were detected to be carriers for Pompe disease (frequency one in 67). None of the 88 couples screened were found to be carriers for the same disorder. The pathogenic variants observed in many disorders (such as deafness, cystic fibrosis, Pompe disease, Canavan disease, primary hyperoxaluria, junctional epidermolysis bullosa, galactosemia, medium chain acyl CoA deficiency etc.) were different from those commonly observed in the West. Conclusion: A higher carrier frequency for genetic deafness, cystic fibrosis and Pompe disease was unexpected, and contrary to the generally held view about their prevalence in Asian Indians. In spite of the small sample size, this study would suggest that population-based carrier screening panels for India would differ from those in the West, and need to be selected with due care. Testing should comprise the study of all the coding exons with its boundaries in the genes through NGS, as all the variants are not well characterized. Only study of entire coding regions in the genes will detect carriers with adequate efficiency, in order to reduce the burden of genetic disorders in India and other resource poor countries.

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“…Biallelic variants in the GBA gene causing a deficiency of acid β-glucosidase and cause Gaucher disease, the most common lysosomal storage disorder in the world [ 75 ]. The variant p.Gly289Ala and p.Leu483Pro were observed in one individual in the present cohort.…”

Section: Discussionmentioning

confidence: 99%

NGS-based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background To determine the carrier frequency and pathogenic variants of common genetic disorders in the north Indian population by using next generation sequencing (NGS). Methods After pre-test counselling, 200 unrelated individuals (including 88 couples) were screened for pathogenic variants in 88 genes by NGS technology. The variants were classified as per American College of Medical Genetics criteria. Pathogenic and likely pathogenic variants were subjected to thorough literature-based curation in addition to the regular filters. Variants of unknown significance were not reported. Individuals were counselled explaining the implications of the results, and cascade screening was advised when necessary. Results Of the 200 participants, 52 (26%) were found to be carrier of one or more disorders. Twelve individuals were identified to be carriers for congenital deafness, giving a carrier frequency of one in 17 for one of the four genes tested (SLC26A4, GJB2, TMPRSS3 and TMC1 in decreasing order). Nine individuals were observed to be carriers for cystic fibrosis, with a frequency of one in 22. Three individuals were detected to be carriers for Pompe disease (frequency one in 67). None of the 88 couples screened were found to be carriers for the same disorder. The pathogenic variants observed in many disorders (such as deafness, cystic fibrosis, Pompe disease, Canavan disease, primary hyperoxaluria, junctional epidermolysis bullosa, galactosemia, medium chain acyl CoA deficiency etc.) were different from those commonly observed in the West. Conclusion A higher carrier frequency for genetic deafness, cystic fibrosis and Pompe disease was unexpected, and contrary to the generally held view about their prevalence in Asian Indians. In spite of the small sample size, this study would suggest that population-based carrier screening panels for India would differ from those in the West, and need to be selected with due care. Testing should comprise the study of all the coding exons with its boundaries in the genes through NGS, as all the variants are not well characterized. Only study of entire coding regions in the genes will detect carriers with adequate efficiency, in order to reduce the burden of genetic disorders in India and other resource poor countries.

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Diagnosis and Management of Gaucher Disease in India – Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics

Cited by 27 publications

References 52 publications

Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study

Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study

NGS based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study.

NGS-based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study

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