Abstract
Objectives
Evaluation of clinical, biochemical and molecular analysis of Pakistani patients with hepatic GSDs.
Methods
Medical charts, biochemical, histopathological and molecular results of patients with hepatic GSD were reviewed.
Results
Out of 55 GSD patients, 41 (74.5%) were males and 14 (25.5%) were females with consanguinity in 50 (91%) patients. The median age of initial symptoms, clinic diagnosis and molecular diagnosis were 450 (IQR: 270–960), 1,095 (IQR: 510–1,825) and 1717 (IQR: 796–3,011) days, respectively. Molecular analysis and enzyme activity was available for 33 (60%) and two patients, respectively. GSD III (n=9) was most prevalent followed by GSD Ib (n=7), GSD IXc (n=6), GSD VI (n=4), GSD Ia (n=3), GSD XI (n=3), GSD IXb (n=2) and GSD IXa (n=1). In patients (n=33) who underwent molecular analysis; 19 different variants in eight genes associated with GSD were identified. We also report five novel variants, two in SLC37A4, one in AGL and two in PYGL contributing to the diagnosis of GSD Ib, GSD III and GSD VI, respectively.
Conclusions
Fifty-five patients of GSDs in 26 families from a single care provider indicate a relatively high frequency of GSD in Pakistan, with multiple unrelated families harboring identical disease-causing variants, on molecular analysis, including two known pathogenic variants in SLC37A4 and PHKG2, and a novel variant in AGL.
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Research funding: None declared.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable as it was a retrospective chart review.
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Ethical approval: The study was approved from the institutional ethical review committee of the Aga Khan University (ERC # 2020-5049-11210).
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