Affiliation:
1. Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
2. The Children Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
Abstract
Lysosomal storage disorders (LSDs) are a large group of inborn errors of
metabolism each caused by genetic mutations of a particular lysosomal
protein encoding gene. These inherited conditions are characterized by
lysosomal dysfunction with wide variety of organ impact sometimes organ
failure with growing age. Neurological complications in LSD cases range from
severe neurodegenerations in 70% cases to mild symptoms or absence of
neuropathy in others. Each LSD is monogenic but heterogeneous from a
molecular standpoint with a large number of mutations described in the
respective gene. Some mutations are particular to specific populations,
reflecting consequences of founder effect. Present study aimed to access the
demographic and clinical profiles of forty-five LSD affected families
enrolled during January 2018 to December 2019 at local hospitals to find out
neurological symptoms in Pakistani LSD cases. Furthermore, molecular genetic
analysis of Gaucher?s disease affected families was performed to unveil
underlying disease causing mutation/s. Neurological manifestations were
present in twenty-eight families including eleven Mucopolysaccharidosis-1
(MPS-I), four Gaucher?s disease (GD) and all MPS-II, MPS-III, Niemann-Pick,
Griscelli and Chediak-Higashi cases. Neurological involvement was not found
in eight MPS-I, one GD, all MPS-IV and Pycnodysostosis affected families.
Screening of GBA gene in GD families revealed a reported missense mutation
p.L483P in all analyzed families. Clinical heterogeneity of MPS-1 and GD is
evident from literature however mutational analysis of all enrolled GD
families depicted segregation of a reported missense variant p.L483P of GBA
gene with disease phenotype in all families. Our findings highlight
importance of homeostatic role of lysosomes in neuronal development as
twenty eight out of forty families had neurological manifestations.
Furthermore, identification of same mutation in GD patients with or without
neuronal involvement may be related to some unknown differences in the
expression of genetic modifiers or exposure to environmental triggers.
Publisher
National Library of Serbia
Cited by
1 articles.
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