Abstract
BackgroundPompe disease (PD) is a serious genetic disorder caused by deficiency of acid α-glucosidase (GAA) and subsequent glycogen accumulation inside lysosomes. This study included a cohort of 5 Egyptian infants (1–8 months old) with far lower than average normal GAA activity and clinical signs of PD in 4 of the 5 cases. The fifth case was discovered by newborn screening (NBS). Molecular analysis of the GAA gene was performed to confirm the diagnosis and identify the underlying mutation.ResultsThe study identified the causative mutations [c.1193T > C (p.Leu398Pro), c.1134C > G (p.Tyr378*) & c.1431del (p.Ile477Metfs*43)] in 4 cases. However, molecular analysis reversed the expected pathologic state in the fifth infant, where his reduced enzymatic activity was related to the presence of pseudodeficiency allele c.868A > G (p.Asn290Asp) in addition to heterozygous disease-causing mutation c.2238G > C (p.Trp746Cys).ConclusionThis study presents the first molecular analysis of GAA gene in Egypt and has thrown some light on the importance of PD molecular diagnosis to provide precise diagnosis and enable therapeutic commencement in affected subjects.
Highlights
Pompe disease (PD) is a serious genetic disorder caused by deficiency of acid α-glucosidase (GAA) and subsequent glycogen accumulation inside lysosomes
According to the disease age of onset, PD is classified into two main clinical forms: infantile-onset PD (IOPD) which begins within the first months of life, and lateonset PD (LOPD) which appears any time after the first
All patients showed positive consanguinity except one whose diminished enzyme activity was detected throughout newborn screening (NBS) for inborn errors of metabolism (IEMs) without observation of any disease manifestations
Summary
Pompe disease (PD) is a serious genetic disorder caused by deficiency of acid α-glucosidase (GAA) and subsequent glycogen accumulation inside lysosomes. This study included a cohort of 5 Egyptian infants (1–8 months old) with far lower than average normal GAA activity and clinical signs of PD in 4 of the 5 cases. Pompe disease (PD), called glycogen storage disease type II (GSD II) or acid maltase deficiency (AMD) (MIM# 232300), is a genetic neuromuscular disorder with an autosomal recessive mode of inheritance. It is caused by mutations in acid alpha-glucosidase gene (GAA)which is localized to chromosome 17q25.2- q25.3 and consists of 20 exons (exon 1 is noncoding). Very rare occurrence rate of PD has been documented in some countries such as Sweden and Finland [6, 7]
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