TY - JOUR
T1 - Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan
AU - Ahmed, Sibtain
AU - Akbar, Fizza
AU - Ali, Amyna Jaffar
AU - Afroze, Bushra
N1 - Publisher Copyright:
© 2022 Walter de Gruyter GmbH, Berlin/Boston.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - 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.
AB - 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.
KW - Pakistan
KW - biochemical
KW - glycogen storage diseases
KW - hepatic
KW - next generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=85122617838&partnerID=8YFLogxK
U2 - 10.1515/jpem-2021-0575
DO - 10.1515/jpem-2021-0575
M3 - Article
C2 - 34989216
AN - SCOPUS:85122617838
SN - 0334-018X
VL - 35
SP - 373
EP - 385
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 3
ER -