Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients
Abstract Fabry disease (FD) is a treatable X linked lysosomal storage disorder with a wide phenotypic spectrum. There is a scarcity of published data on the burden of FD in India. This study evaluates the clinical and molecular spectrum of Indian patients with FD. In this multicentric study involvin...
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| Format: | Article |
| Language: | English |
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Wiley
2020-11-01
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| Series: | JIMD Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jmd2.12156 |
| _version_ | 1818256441313591296 |
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| author | Sheela Nampoothiri Dhanya Yesodharan Amrita Bhattacherjee Hisham Ahamed Ratna Dua Puri Neerja Gupta Madhulika Kabra Prajnya Ranganath Meenakshi Bhat Shubha Phadke Akella Radha Rama Devi Sujatha Jagadeesh Sumita Danda Padmavathy Narayana Sylaja Kausik Mandal Sunita Bijarnia‐Mahay Ravinder Makkar Ishwar Chander Verma Ashwin Dalal Uma Ramaswami |
| author_facet | Sheela Nampoothiri Dhanya Yesodharan Amrita Bhattacherjee Hisham Ahamed Ratna Dua Puri Neerja Gupta Madhulika Kabra Prajnya Ranganath Meenakshi Bhat Shubha Phadke Akella Radha Rama Devi Sujatha Jagadeesh Sumita Danda Padmavathy Narayana Sylaja Kausik Mandal Sunita Bijarnia‐Mahay Ravinder Makkar Ishwar Chander Verma Ashwin Dalal Uma Ramaswami |
| author_sort | Sheela Nampoothiri |
| collection | DOAJ |
| description | Abstract Fabry disease (FD) is a treatable X linked lysosomal storage disorder with a wide phenotypic spectrum. There is a scarcity of published data on the burden of FD in India. This study evaluates the clinical and molecular spectrum of Indian patients with FD. In this multicentric study involving 10 tertiary referral centers in India, we analyzed the clinical course and genotype of 54 patients from 37 families. Family screening identified 19 new patients (35%) from 12 index cases. Then, 33 GLA gene variants were identified in 49/54 (90.7%) which included 11 novel and 22 known pathogenic variants. Of the 54 patients in our cohort, 40 patients had “classical” and 10 patients had a “nonclassical” presentation. The symptoms and signs included kidney dysfunction in 38/54 (70.3%), neuropathic pain in 34/54 (62.9%), left ventricular hypertrophy in 22/49 (44.8%) and stroke in 5/54 (9.2%). Female heterozygotes were 10/54 (18.5%) of whom 2 were index cases. There was a significant delay in reaching the diagnosis of 11.7 years. Enzyme replacement therapy was initiated in 28/54 (51.8%) patients with significant improvement of neuropathic pain and gastrointestinal symptoms. This study highlights the clinical presentation and mutational spectrum of FD in India and suggests that family screening and screening of high‐risk groups (hypertrophic cardiomyopathy, idiopathic chronic renal failure and cryptogenic stroke) could be the most cost‐effective strategies for early identification of FD. |
| first_indexed | 2024-12-12T17:27:48Z |
| format | Article |
| id | doaj.art-1fc4e82c88a64b728007b9797e36a37d |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-12T17:27:48Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-1fc4e82c88a64b728007b9797e36a37d2022-12-22T00:17:29ZengWileyJIMD Reports2192-83122020-11-01561829410.1002/jmd2.12156Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patientsSheela Nampoothiri0Dhanya Yesodharan1Amrita Bhattacherjee2Hisham Ahamed3Ratna Dua Puri4Neerja Gupta5Madhulika Kabra6Prajnya Ranganath7Meenakshi Bhat8Shubha Phadke9Akella Radha Rama Devi10Sujatha Jagadeesh11Sumita Danda12Padmavathy Narayana Sylaja13Kausik Mandal14Sunita Bijarnia‐Mahay15Ravinder Makkar16Ishwar Chander Verma17Ashwin Dalal18Uma Ramaswami19Department of Pediatric Genetics Amrita Institute of Medical Sciences and Research Centre Cochin Kerala IndiaDepartment of Pediatric Genetics Amrita Institute of Medical Sciences and Research Centre Cochin Kerala IndiaDiagnostics Division Centre for DNA Fingerprinting and Diagnostics (CDFD) Hyderabad IndiaDepartment of Cardiology Amrita Institute of Medical Sciences and Research Centre Cochin Kerala IndiaInstitute of Genetics and Genomics Sir Ganga Ram Hospital New Delhi IndiaDivision of Genetics, Department of Pediatrics All India Institute of Medical Sciences New Delhi IndiaDivision of Genetics, Department of Pediatrics All India Institute of Medical Sciences New Delhi IndiaDepartment of Medical Genetics Nizam's Institute of Medical Sciences Hyderabad IndiaDepartment of Clinical Genetics Centre for Human Genetics Bangalore IndiaDepartment of Medical Genetics Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow IndiaRainbow Children Hospital Hyderabad IndiaDepartment of Clinical Genetics and Genetic Counseling Mediscan Systems Chennai IndiaDepartment of Clinical Genetics Christian Medical College and Hospital Vellore IndiaComprehensive Stroke Care Program, Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) Trivandrum Kerala IndiaDepartment of Medical Genetics Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow IndiaInstitute of Genetics and Genomics Sir Ganga Ram Hospital New Delhi IndiaSanofi Genzyme New Delhi IndiaInstitute of Genetics and Genomics Sir Ganga Ram Hospital New Delhi IndiaDiagnostics Division Centre for DNA Fingerprinting and Diagnostics (CDFD) Hyderabad IndiaLysosomal Disorders Unit, Institute of Immunity and Transplantation Royal Free London NHS Foundation Trust London UKAbstract Fabry disease (FD) is a treatable X linked lysosomal storage disorder with a wide phenotypic spectrum. There is a scarcity of published data on the burden of FD in India. This study evaluates the clinical and molecular spectrum of Indian patients with FD. In this multicentric study involving 10 tertiary referral centers in India, we analyzed the clinical course and genotype of 54 patients from 37 families. Family screening identified 19 new patients (35%) from 12 index cases. Then, 33 GLA gene variants were identified in 49/54 (90.7%) which included 11 novel and 22 known pathogenic variants. Of the 54 patients in our cohort, 40 patients had “classical” and 10 patients had a “nonclassical” presentation. The symptoms and signs included kidney dysfunction in 38/54 (70.3%), neuropathic pain in 34/54 (62.9%), left ventricular hypertrophy in 22/49 (44.8%) and stroke in 5/54 (9.2%). Female heterozygotes were 10/54 (18.5%) of whom 2 were index cases. There was a significant delay in reaching the diagnosis of 11.7 years. Enzyme replacement therapy was initiated in 28/54 (51.8%) patients with significant improvement of neuropathic pain and gastrointestinal symptoms. This study highlights the clinical presentation and mutational spectrum of FD in India and suggests that family screening and screening of high‐risk groups (hypertrophic cardiomyopathy, idiopathic chronic renal failure and cryptogenic stroke) could be the most cost‐effective strategies for early identification of FD.https://doi.org/10.1002/jmd2.12156chronic renal failureFabry diseaseGLA mutationhypertrophic cardiomyopathylate onsetstroke |
| spellingShingle | Sheela Nampoothiri Dhanya Yesodharan Amrita Bhattacherjee Hisham Ahamed Ratna Dua Puri Neerja Gupta Madhulika Kabra Prajnya Ranganath Meenakshi Bhat Shubha Phadke Akella Radha Rama Devi Sujatha Jagadeesh Sumita Danda Padmavathy Narayana Sylaja Kausik Mandal Sunita Bijarnia‐Mahay Ravinder Makkar Ishwar Chander Verma Ashwin Dalal Uma Ramaswami Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients JIMD Reports chronic renal failure Fabry disease GLA mutation hypertrophic cardiomyopathy late onset stroke |
| title | Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients |
| title_full | Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients |
| title_fullStr | Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients |
| title_full_unstemmed | Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients |
| title_short | Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients |
| title_sort | fabry disease in india a multicenter study of the clinical and mutation spectrum in 54 patients |
| topic | chronic renal failure Fabry disease GLA mutation hypertrophic cardiomyopathy late onset stroke |
| url | https://doi.org/10.1002/jmd2.12156 |
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