Abstract:Background
Mucopolysaccharidosis IVA (Morquio syndrome A, MPS IVA) is an autosomal recessive lysosomal storage disorder caused due to biallelic variants in the N-acetylgalactoseamine-6-sulfate sulfatase (GALNS) gene. The mutation spectrum in this condition is determined amongst sub-populations belonging to the north, south and east India geography, however, sub-populations of west Indian origin, especially Gujarati-Indians, are yet to be studied. We aimed to analyse the variants present in the … Show more
“…Subsequently, low activity of enzyme N ‐acetylgalactosamine 6‐sulphatase in these patients confirmed the diagnosis of MPS IVA. The founder variant p.Pro77Arg in the GALNS gene, previously reported in the Patel community from Gujarat, India, 31 was identified in patient P14. Patients P16–P18 suspected with MPS I, showed mild coarse face, with corneal clouding seen only in patient P17.…”
Lysosomal storage disorders (LSDs) in adults have milder phenotype and variable age at presentation. Several studies have described the phenotype, genotype and treatment outcomes for adult‐onset LSDs like Gaucher, Fabry, Pompe disease and others. We describe the first systematic study on the occurrence of LSDs in an adult population from India. It describes, the key clinical signs seen in these patients and those from literature review that can aid in early detection. Of 2102 biochemically diagnosed LSDs cases, 32 adult patients were identified with LSDs. Based on the clinical suspicion, screening test and enzyme study was carried out. Twenty‐two patients were subjected to a genetic study to identify the causative variant in a respective gene. Of the 32 adult patients, we observed a maximum percentage of 37.5% (n = 12) cases with Gaucher disease, followed by 13% (n = 4) with Fabry disease. We found 10% of cases with MPS IVA and MPS I, and 9% cases with Pompe. Single case of adult mucolipidosis III and two cases each of Type 1 Sialidosis, Niemann‐Pick disease B and metachromatic leukodystrophy were identified. We observed two common variants p.Leu483Pro and p.Ala487Thr in the GBA1 gene in 23% of Indian patients with adult Gaucher disease. No common variants were observed in other aforementioned LSDs. Study identified 50% of Fabry patients and 4% of Gaucher patients diagnosed at our centre to be adults. The prevalence of adult Pompe patients was low (3.4%) as compared to 80% reported in the Caucasian population. Adult LSDs such as, MPS III, GM1/GM2 gangliosidosis and Krabbe disease were not identified in our cohort.
“…Subsequently, low activity of enzyme N ‐acetylgalactosamine 6‐sulphatase in these patients confirmed the diagnosis of MPS IVA. The founder variant p.Pro77Arg in the GALNS gene, previously reported in the Patel community from Gujarat, India, 31 was identified in patient P14. Patients P16–P18 suspected with MPS I, showed mild coarse face, with corneal clouding seen only in patient P17.…”
Lysosomal storage disorders (LSDs) in adults have milder phenotype and variable age at presentation. Several studies have described the phenotype, genotype and treatment outcomes for adult‐onset LSDs like Gaucher, Fabry, Pompe disease and others. We describe the first systematic study on the occurrence of LSDs in an adult population from India. It describes, the key clinical signs seen in these patients and those from literature review that can aid in early detection. Of 2102 biochemically diagnosed LSDs cases, 32 adult patients were identified with LSDs. Based on the clinical suspicion, screening test and enzyme study was carried out. Twenty‐two patients were subjected to a genetic study to identify the causative variant in a respective gene. Of the 32 adult patients, we observed a maximum percentage of 37.5% (n = 12) cases with Gaucher disease, followed by 13% (n = 4) with Fabry disease. We found 10% of cases with MPS IVA and MPS I, and 9% cases with Pompe. Single case of adult mucolipidosis III and two cases each of Type 1 Sialidosis, Niemann‐Pick disease B and metachromatic leukodystrophy were identified. We observed two common variants p.Leu483Pro and p.Ala487Thr in the GBA1 gene in 23% of Indian patients with adult Gaucher disease. No common variants were observed in other aforementioned LSDs. Study identified 50% of Fabry patients and 4% of Gaucher patients diagnosed at our centre to be adults. The prevalence of adult Pompe patients was low (3.4%) as compared to 80% reported in the Caucasian population. Adult LSDs such as, MPS III, GM1/GM2 gangliosidosis and Krabbe disease were not identified in our cohort.
“… 5 , 6 Their study also demonstrated the presence of a founder variant for Tay-Sachs and Morquio-A disease in a particular community of Gujarat, India. 6 , 7 They have also observed a common variant L444P in the GBA1 gene for Gaucher disease patients pan India. 8 Fig.…”
Section: Introductionmentioning
confidence: 96%
“… 19 A recent study by Sheth and his group has shown the presence of a founder variant P77R in the GALNS gene in MPS IVA patients from Gujarat in a particular ethnicity. 7 Another group of LSDs consisting of Batten disease, Pompe disease, and Fabry disease has a low prevalence in the country. However, in absence of accurate data, the observed low percentages may be due to lack of awareness among clinicians and a dearth of diagnostic facilities across the country.…”
Section: Introductionmentioning
confidence: 99%
“…2014 42 p.Pro77Arg 14/23 families Gujarat Sheth et al. 2022 7 (DHR-ICMR-NTF-LSD) MPS VI p.W450C (c.1350 G>C) p.L98R: Founder variant 4/14 families 2/8 families Pan-India South-India Uttarilli et al. 2015 43 Mathew et al.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
