Clinical And Genetic Analysis Of Two Cases Of Glycogen Storage Diseases

Background:Glycogen storage diseases (glycogen storage diseases, GSD) are a series of glycogen metabolic disorders due to deficiencies in enzymes participating in glycogen metabolism. There are at least 16 types of glycogen storage diseases. GSD type III is characterized by progressive muscle weakness, due to the deficiency of glycogen debranching enzyme (GDE), which is encoded by AGL.170 mutations have been reported so far. The prevalent mutations of AGL in GSD type III vary among the ethnic groups, and p.R864X is a relatively frequent mutation. More than 50 cases were reported in China mainland. GSD type V is characterized by exercise intolerance, attributed to the deficiency of muscle glycogen phosphorylase (PYGM), which is encoded by PYGM. By now 147 mutations have been identified. p.R50X is the most frequent mutation among Caucasians. But in China mainland no patients with GSD type V were reported.Purposes:To explore clinical features, laboratory examinations and pathological mutations of GSD type â…¢ and GSD type V.Methods:We report one case of GSD type â…¢ and one of GSD type V. Clinical manifestations, laboratory examinations, muscle biopsy and gene mutation were analyzed in the patients.Results:1 patient with GSD type â…¢, male, manifested with muscle weakness, both proximal and distal muscle affected, abdominal distension, hepatomegaly and moderately elevated serum CK. Muscle biopsy pathology illustrated a large amount of big vacuoles in muscle fibers, muscle fibers positive in periodic acid Schiff staining. Mutation:homozygous mutation of c.2979C> T in exon 22 of AGL, p. R977X, a nonsense mutation has been reported.1 patient with GSD type V, male, denying positive family history, manifested with mild muscle weakness, reduced exercise tolerance, elevated serum CK. Muscle biopsy indicates a large number of small vacuoles in muscle fiber, muscle fibers positive in periodic acid Schiff staining. Mutation:homozygous mutation of c. 1142T>C in exon 10 of PYGM, p. L381P, which has been reported as a missense mutation.Conclusions:1. Glycogen storage diseases manifest limb muscle strength loss or decreased exercise tolerance, mostly bilaterally affected. Patients with GSD type â…¢ manifest muscle weakness, with or without liver dysfunction. GSD type â…¤ is characterized by decreased exercise tolerance, second wind phenomenon, and some patients suffered from mild muscle weakness. Muscle biopsy demonstrated glycogen accumulation in both GSD type â…¢ and GSD type â…¤ patients.2. The patient with GSD type â…¢ was detected with c.2979C>T homozygous mutation, which has been reported. The patient with GSD type â…¤ was detected with c.1142 T>C heterozygous mutation, which is a new mutation that has not been reported.3. Genetic analysis is effective in glycogen storage diseases diagnosis, it is also essential for geno-phenotype relationship studies.