Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria
ABSTRACT Homocystinuria due to cystathionine beta‐synthase (CBS) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait. Spectrum of genetic variants in CBS gene and their correlation with the phenotypes of homocystinuria in Sri Lankan patients have not been reported to da...
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Wiley
2025-01-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12470 |
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| author | Hewa Warawitage Dilanthi Kandana Liyanage Subhashinie Jayasena Nambage Dona Priyani Dhammika Neluwa Liyanage Ruwan Indika Matara Mahavidanage Nishani De Silva Imalke Kankananarachchi Pushpa Malkanthi Gardiye Punchihewa Dharma Irugalbandara Sabine Schroeder Kosala Karunaratne Eresha Jasinge |
| author_facet | Hewa Warawitage Dilanthi Kandana Liyanage Subhashinie Jayasena Nambage Dona Priyani Dhammika Neluwa Liyanage Ruwan Indika Matara Mahavidanage Nishani De Silva Imalke Kankananarachchi Pushpa Malkanthi Gardiye Punchihewa Dharma Irugalbandara Sabine Schroeder Kosala Karunaratne Eresha Jasinge |
| author_sort | Hewa Warawitage Dilanthi |
| collection | DOAJ |
| description | ABSTRACT Homocystinuria due to cystathionine beta‐synthase (CBS) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait. Spectrum of genetic variants in CBS gene and their correlation with the phenotypes of homocystinuria in Sri Lankan patients have not been reported to date. The objective of this study was to identify the genotypes and genotype–phenotype correlations in a cohort of Sri Lankan patients with homocystinuria due to CBS deficiency. We determined the variants in CBS gene in 14 Sri Lankan patients with homocystinuria, from 9 unrelated families. The clinical features and the biochemical response to pyridoxine were studied for further correlations. Among the 14 patients, the common clinical features were ectopia lentis (100%), intellectual disability (92%) and marfanoid features (78%) at presentation while three of them had developed osteoporosis (21%). Median age at diagnosis was 8 years (range 2–12). Three pathogenic variants (c.1006C>T, c.785C>T and c.19del) and two likely pathogenic variants (c.869C>T, c.772G>A) in CBS gene were identified. Thirteen patients with homozygous genotypes were non‐responsive to pyridoxine while the only patient with the compound heterozygous genotype (c.869C>T/c.772G>A) responded to pyridoxine treatment. The genotypic spectrum observed in Sri Lankan patients is unique and mostly associated with pyridoxine non‐responsiveness. The majority of the patients were identified clinically at a later stage of the disease due to lack of a screening programme in the country. Therefore, it is important to improve the awareness of the disease among the clinicians in the interest of early diagnosis and early commencement of metabolic treatment. |
| format | Article |
| id | doaj-art-7d3dc0b2f9ce402292ccc995c486b20a |
| institution | Kabale University |
| issn | 2192-8312 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj-art-7d3dc0b2f9ce402292ccc995c486b20a2025-01-28T07:38:32ZengWileyJIMD Reports2192-83122025-01-01661n/an/a10.1002/jmd2.12470Genotypic Spectrum in a Cohort of Sri Lankan Patients With HomocystinuriaHewa Warawitage Dilanthi0Kandana Liyanage Subhashinie Jayasena1Nambage Dona Priyani Dhammika2Neluwa Liyanage Ruwan Indika3Matara Mahavidanage Nishani De Silva4Imalke Kankananarachchi5Pushpa Malkanthi Gardiye Punchihewa6Dharma Irugalbandara7Sabine Schroeder8Kosala Karunaratne9Eresha Jasinge10Department of Chemical Pathology Lady Ridgeway Hospital for Children Colombo Sri LankaDepartment of Chemical Pathology Lady Ridgeway Hospital for Children Colombo Sri LankaDepartment of Chemical Pathology Lady Ridgeway Hospital for Children Colombo Sri LankaDepartment of Chemical Pathology Lady Ridgeway Hospital for Children Colombo Sri LankaDepartment of Chemical Pathology Lady Ridgeway Hospital for Children Colombo Sri LankaDepartment of Paediatrics, Faculty of Medicine University of Ruhuna Galle Sri LankaPaediatric Unit Lady Ridgeway Hospital for Children Colombo Sri LankaOphthalmology Unit Lady Ridgeway Hospital for Children Colombo Sri LankaCentogene GmbH Rostock GermanyPaediatric Unit Lady Ridgeway Hospital for Children Colombo Sri LankaDepartment of Chemical Pathology Lady Ridgeway Hospital for Children Colombo Sri LankaABSTRACT Homocystinuria due to cystathionine beta‐synthase (CBS) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait. Spectrum of genetic variants in CBS gene and their correlation with the phenotypes of homocystinuria in Sri Lankan patients have not been reported to date. The objective of this study was to identify the genotypes and genotype–phenotype correlations in a cohort of Sri Lankan patients with homocystinuria due to CBS deficiency. We determined the variants in CBS gene in 14 Sri Lankan patients with homocystinuria, from 9 unrelated families. The clinical features and the biochemical response to pyridoxine were studied for further correlations. Among the 14 patients, the common clinical features were ectopia lentis (100%), intellectual disability (92%) and marfanoid features (78%) at presentation while three of them had developed osteoporosis (21%). Median age at diagnosis was 8 years (range 2–12). Three pathogenic variants (c.1006C>T, c.785C>T and c.19del) and two likely pathogenic variants (c.869C>T, c.772G>A) in CBS gene were identified. Thirteen patients with homozygous genotypes were non‐responsive to pyridoxine while the only patient with the compound heterozygous genotype (c.869C>T/c.772G>A) responded to pyridoxine treatment. The genotypic spectrum observed in Sri Lankan patients is unique and mostly associated with pyridoxine non‐responsiveness. The majority of the patients were identified clinically at a later stage of the disease due to lack of a screening programme in the country. Therefore, it is important to improve the awareness of the disease among the clinicians in the interest of early diagnosis and early commencement of metabolic treatment.https://doi.org/10.1002/jmd2.12470betainecystathionine beta‐synthasecystathionine beta‐synthase deficiencyhomocystinuriapyridoxine |
| spellingShingle | Hewa Warawitage Dilanthi Kandana Liyanage Subhashinie Jayasena Nambage Dona Priyani Dhammika Neluwa Liyanage Ruwan Indika Matara Mahavidanage Nishani De Silva Imalke Kankananarachchi Pushpa Malkanthi Gardiye Punchihewa Dharma Irugalbandara Sabine Schroeder Kosala Karunaratne Eresha Jasinge Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria JIMD Reports betaine cystathionine beta‐synthase cystathionine beta‐synthase deficiency homocystinuria pyridoxine |
| title | Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria |
| title_full | Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria |
| title_fullStr | Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria |
| title_full_unstemmed | Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria |
| title_short | Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria |
| title_sort | genotypic spectrum in a cohort of sri lankan patients with homocystinuria |
| topic | betaine cystathionine beta‐synthase cystathionine beta‐synthase deficiency homocystinuria pyridoxine |
| url | https://doi.org/10.1002/jmd2.12470 |
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