Spectrum of ARSA variations in Asian Indian patients with Arylsulfatase A deficient metachromatic leukodystrophy

Metachromatic leukodystrophy genotypes in The Netherlands reveal novel pathogenic ARSA variants in non-Caucasian patients

“…More phenotype information on pathogenic ARSA variants will also help interpreting results from the pilot [31,32]. Finally, Narayanan et al recently reported 36 ARSA variants in MLD patients from India, and no less than sixteen of them were novel [33].…”

“…A few examples are the c.847G > A, p.(Asp283Asn), c.853G > A, p.(Asp285Asn), and c.1031C > A, p.(Ala344Asp) variants in Sri Lanka [ 27 ]; the c.256C > G, p.(Arg86Gly), c.344 T > C, p.(Leu115Pro), and c.693C > A, p.(His231Gln) variants in respectively Jordan, Pakistan, and Tunisia [ 28 – 30 ]; and the c.1070G > T, p.(Gly357Val), c.585G > T, p.(Trp195Cys), c.849C > G, p.(Asp283Glu), and c.911A > G, p.(Lys304Arg) variants in Iran [ 31 , 32 ]. Finally, Narayanan et al recently reported 36 ARSA variants in MLD patients from India, and no less than sixteen of them were novel [ 33 ].…”

Three novel variants in the arylsulfatase A (ARSA) gene in patients with metachromatic leukodystrophy (MLD)

“…MLD is classified in three subtypes depending on the age of onset as; infantile (0–2 years); juvenile with subtypes of early (3–6 years) and late juvenile (7–16) and adult. The onset of the adult form is after sexual maturity, sometimes not until the fourth or fifth decade of life [3].…”

Clinical and genetic spectrum of 104 Indian families with central nervous system white matter abnormalities

“…Cohorts of individuals with targeted testing including restriction fragment length polymorphisms, amplification-refractory mutation system based polymerase chain reaction, and Sanger sequencing for common and recognisable phenotypes, especially for recurrent genetic variants have been reported from India previously. 32,33 The diagnostic yield of targeted testing is likely to be variable and dependent on the cohort selection as well as the clinical expertise available with the team. Richards et al reported the diagnostic yield of targeted genetic testing in a cohort of individuals with leukodystrophies to be 34% with average time of diagnosis being one-and-half years.…”

“…Several disorders with CNS WMAs have been reported from India earlier including a recently reported a cohort of 50 individuals with relatively common and recognisable disorders of CNS WMAs 12 . Multiple case series describing the genotypic spectrum of relatively common and clinically recognisable disorders like metachromatic leukodystrophy (67 families), 32,33 megalencephalic leukoencephalopathy with subcortical cysts (39 families) 34 and Tay‐Sachs disease (28 families) 35 have been published. Multiple case reports describe individuals with hypomyelination with hypodontia and hypogonadotropic hypogonadism, 36 Krabbe disease, 37 Alexander disease, 38 vanishing white matter disease, 39 Canavan disease, 40 leukoencephalopathy with brainstem and spinal cord involvement, 41 glutaric aciduria, 42 GM1 gangliosidosis, 43 Coats plus syndrome, 44 ribose 5‐phosphate isomerase deficiency, 45 TUB4A1 related hypomyelinating leukodystrophy, 46 homocystinuria due to MTHFR deficiency 47 and adult onset disorders like cerebral autosomal‐dominant arteriopathy with subcortical infarcts (CADASIL), 48 CARASIL, 49 diffuse hereditary leukoencephalopathy with spheroids 50 and X‐linked adrenoleukodystrophy 51–53 .…”