Case Report: Identification of Compound Heterozygous Mutations in a Patient With Late-Onset Glycogen Storage Disease Type II (Pompe Disease)

Front Neurol. 2022 Mar 21;13:839263. doi: 10.3389/fneur.2022.839263.

PMID: 35386406

Huiting Zhang, Jun Chen, Yuchang Zhu

Highlights: Mutational analysis of GAA and muscle biopsy are crucial in the diagnosis of Pompe disease.

Abstract

Background: Acid α-glucosidase enzyme (GAA) deficits are associated with Pompe disease, an autosomal recessive hereditary lysosomal disorder that causes a buildup of glycogen in many tissues, particularly skeletal muscles. Adult-onset late-onset Pompe disease (LOPD) is a proximal myopathy that progresses slowly and eventually affects the respiratory muscles, leading to respiratory failure.

Objective: In this study, a 22-year-old Chinese woman is described who had experienced respiratory and ambulatory impairment for two months and had struggled to endure strenuous physical exercise since she was a young child.

Results: According to the Medical Research Council (MRC) score, she had bilateral upper limb strength ratings of 4/5 and lower limb strength ratings of 3/5 at the time of admission. The patient had compound heterozygotes with a missense mutation (c.2238G>C, p.Trp746Cys) and a newly discovered 4 nt deletion of coding sequence (deletion nt 1411_1414) in one of the acid α-glucosidase alleles. However, LOPD has not been associated with this mutation, only infant-onset Pompe disease (IOPD). It's interesting to note that this deletion mutation, which was deemed pathogenic, was not discovered in the patient's family. In the subsarcolemmal region of the muscle, a muscle sample revealed sporadic vacuoles containing basophilic granules that were intensely stained by periodic acid-Schiff (PAS). Lactate dehydrogenase and creatine kinase MB isoenzyme (CK-MB) levels were significantly higher than expected, according to laboratory studies (LDH). The diagnosis of GAA activity deficiency (0-3.78 nmol/1 h/mg) was not possible with the GAA level of 9.77 nmol/1 h/mg.

Conclusion: In conclusion, GAA mutational analysis and muscle biopsy are essential for identifying Pompe disease.

Keywords: acid α-glucosidase enzyme, glycogen storage disease type II, late-onset Pompe disease, metabolic myopathy