Sheth Jayesh, Nair Aadhira, Bhavsar Riddhi, Godbole Koumudi, Datar Chaitanya, Nampoothiri Sheela, Panigrahi Inusha, Shah Heli, Bajaj Shruti, Tayade Naresh, Bhardwaj Naveen, Sheth Harsh
Department of Molecular and Biochemical Genetics FRIGE's Institute of Human Genetics Ahmedabad India.
Department of Clinical Genetics Deenanath Mangeshkar Hospital & Research Centre Pune India.
JIMD Rep. 2024 Jan 2;65(2):85-101. doi: 10.1002/jmd2.12407. eCollection 2024 Mar.
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% ( = 12) cases with Gaucher disease, followed by 13% ( = 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 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.
成人溶酶体贮积症（LSDs）具有较温和的表型，发病年龄各异。多项研究描述了成人起病的LSDs（如戈谢病、法布里病、庞贝病等）的表型、基因型和治疗结果。我们描述了对印度成年人群中LSDs发病情况的首次系统性研究。它描述了这些患者以及文献综述中有助于早期检测的关键临床体征。在2102例经生化诊断的LSDs病例中，确定了32例成年LSDs患者。基于临床怀疑，进行了筛查试验和酶学研究。22例患者接受了基因研究以确定各自基因中的致病变异。在这32例成年患者中，我们观察到戈谢病病例占比最高，为37.5%（n = 12），其次是法布里病，占13%（n = 4）。我们发现10%的病例为MPS IVA和MPS I，9%的病例为庞贝病。确诊了1例成人黏脂贮积症III型，以及各2例1型唾液酸沉积症、尼曼-匹克病B型和异染性脑白质营养不良。我们在23%的成年戈谢病印度患者中观察到该基因中有两个常见变异p.Leu483Pro和p.Ala487Thr。在其他上述LSDs中未观察到常见变异。研究发现，在我们中心确诊的法布里病患者中有50%为成年人，戈谢病患者中有4%为成年人。与白种人群中报告的80%相比，成年庞贝病患者的患病率较低（3.4%） .在我们的队列中未发现成人MPS III、GM1/GM2神经节苷脂贮积症和克拉伯病等LSDs。
