Clinical, muscle pathology and molecular biological features of late⁃onset glycogen storage disease typeⅡ

Abstract

Objective To summarize the clinical, muscle pathology and molecular biological features of late⁃onset glycogen storage disease type Ⅱ (GSDⅡ). Methods and Results Five patients with late⁃onset GSD Ⅱ diagnosed and treated in The Fifth Affiliated Hospital of Zhengzhou University from January 2013 to January 2020 were selected. The main clinical manifestations of 5 patients were weakness of raising the head, weakness of the proximal extremities, decreased muscle tone, fatigue intolerance, and dyspnea. The activity of acid α⁃glucosidase (GAA) was significantly reduced. HE staining of muscular tissues in 5 patients showed vacuole⁃like changes of different sizes, different numbers, and irregular shapes in most muscle fibers. Modified Gomori trichrome (MGT) staining showed a large number of blue and purple particles deposited in the vacuole. Periodic acid⁃Schiff (PAS) staining showed the glycogen content in the vacuoles were increased in 4 cases, and the glycogen content in the vacuoles were lost in one case. GAA gene testing showed that 9 mutations were detected in 5 patients, and 4 cases were compound heterozygous mutations, which were derived from father and mother respectively. The c.1320_1322delGAT (p.Met440del) was a deletion mutation, c.2331G＞C (p.Thr777Thr) was a synonymous mutation, c.2237G＞A (p.Trp746*) was a nonsense mutation, c.877G＞A (p.Gly293Arg) was a missense mutation, c.2238G＞C (p.Trp746Cys) was a missense mutation, c.784G＞A (p.Glu262Lys) was a missense mutation, c.2014C＞T (p.Arg672Trp) was a missense mutation, and c. 2332⁃2A＞G was a splicing mutation. One case was homozygous mutation of c. 1432G＞A (p. Gly478Arg), which originated from the mother. Among them, c. 2331G＞C, c. 1432G＞A and c. 2332⁃2A＞G were reported for the first time at home and abroad. Conclusions The clinical manifestations of late⁃onset GSD Ⅱ are weakness of proximal limbs and dyspnea. The activity of GAA in peripheral serum is decreased significantly. Muscle tissue pathology is characteristic. GAA gene mutations are mainly compound heterozygous mutation, c.2331G＞C, c.1432G＞A and c.2332⁃2A＞G are new mutations, which extended the mutation spectrum of GAA gene.

doi：10.3969/j.issn.1672⁃6731.2021.06.007