Early Cardiac Involvement in Late-Onset Pompe Disease: A Case Report from an Iranian Consanguineous Family.
Year: 2026
Type: article
Study design: Case Report
Abstract: Pompe disease (glycogen storage disease type II) is a rare autosomal recessive lysosomal storage disorder caused by GAA gene mutations, leading to acid α-glucosidase deficiency and glycogen accumulation in multiple tissues. Late-Onset Pompe Disease (LOPD) typically manifests after infancy without significant cardiac involvement. The present study reports a 16-year-old Iranian girl of Baloch ethnicity, born to consanguineous parents, who presented at age 11 with progressive proximal muscle weakness, waddling gait, scoliosis, dysphagia, dyspnea, and mild conductive hearing loss. Developmental history revealed delayed walking, recurrent respiratory infections, and echocardiographic evidence of intraventricular septal hypertrophy. Dried Blood Spot (DBS) assay showed markedly reduced GAA activity at pH 3.8 (0.42 nmol/spot/21 h; reference: 1.5-10). Whole-exome sequencing identified a homozygous missense variant c.2015G > A (p.Arg672Gln) in exon 14 of GAA, classified as likely pathogenic by ACMG criteria. Sanger sequencing confirmed segregation. Enzyme replacement therapy with alglucosidase alpha (20 mg/kg biweekly) led to stabilization of disease progression and improvement in motor function over five years. While LOPD usually lacks early cardiac manifestations, our patient exhibited septal hypertrophy and probable cardiomegaly in infancy, suggesting a broader phenotypic range for the p.Arg672Gln mutation. The studied case underlines the importance of considering Pompe disease in patients with unexplained muscle weakness, even when cardiac involvement is present early. Early diagnosis through biochemical and molecular testing, particularly in high-consanguinity regions, allows timely initiation of ERT, potentially improving long-term outcomes in LOPD.
Authors: Atefeh Mir, Shadi Khedri, Zahra Abbasi, Ali Khajeh
Institution: Zahedan University of Medical Sciences
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223043943