The Clinical,Pathological,And Genetic Analysis Of Two Patients Glycogen Storage Disease Type â…¡

Objective: Retrospective analysis of two glycogen storage disease type â…¡ patients with clinical manifestations, pathological features, biochemical characteristics and family gene characteristics, and to further study the correlation between the genotype and phenotype, guiding treatment and genetic counseling.Materials and methods: To collect the clinical data of patients with the disease of glycogen storage disease type â…¡ by muscle biopsy in Jilin University First Hospital Department of Neurology, and then take the patients and their family members in peripheral blood samples for gene detection and GAA activity assay.result:(1) Clinical features: In case 1, male, 13 years old, mainly for the bilateral lower limb weakness, near the end of the main, stair climbing or standing is difficult, after exercise fatigue, occasionally with muscle pain and muscle spasm. In case 2, male, 39 years old, the main manifestations of respiratory muscle weakness, followed by dyspnea, progressive muscle weakness, muscle atrophy.(2) Muscle pathological characteristics: Light microscope hematoxylin eosin(HE) staining showed that muscle fiber cytoplasmic vacuoles formation and basophilic material deposition; periodic acid Schiff reaction(PAS) staining vacuoles visible lesions in the muscle fiber formation.(3) biochemical characteristics: In case 1 proband myocardial enzyme: creatine kinase 1827U/L, lactate dehydrogenase 537U/L, creatine kinase isoenzyme 52.9U/L were increased; liver function: aspartate amino transferase: 143U/L, alanine aminotransferase: 125U/L were increased; activity of acid alpha glucosidase(GAA): 9.28nmol/1h/mg(normal value >14 nmol/1h/mg), the mother of GAA activity: 12.31nmol/1h/mg, the father of GAA activity: 17.34nmol/1h/mg. In case 2 proband myocardial enzyme: creatine kinase 131U/L, lactate dehydrogenase 260U/L, creatine kinase isoenzyme 29.7U/L were increased; liver function: total bilirubin 36.3umol/L, direct bilirubin 10.4umol/L and indirect bilirubin 25.9umol/L, were increased.(4) Genetic testing features: Results of gene detection in 1 cases of proband: GAA gene exon 17 c.2432 del T, frameshift mutation, known as the causative mutation. GAA exon 12, c.1726G>A, Gly576Ser; exon 15, c.2065G>A, Glu689 Lys, missense mutation, as pseudodeficiency allele. Intron 4, IVS4+7ins CAGCGGG mutation, have been reported to have an unknown effect mutation. The father, aunt and grandmother GAA gene exon 17 and intron 4 change in patients with genetic testing results are consistent and exon12, 15 no abnormal sequence; the mother GAA gene significantly in exon 17 of no sequence abnormal, exon 12, 15 and intron 4 change and in gene detection results. Results of gene detection in 2 cases of proband: GAA gene exon 12, c.1669A>T, Ile557 Phe, missense mutation,known as the causative mutation. The exon 17 of GAA gene, c.2338G>A, Val780 Ile, missense mutation,have been reported to have an unknown effect mutation. GAA gene exon 15, c.2065G>A, Glu689 Lys missense mutation, as pseudodefi- ciency allele. The father of GAA gene exon 12, 17 change were consistent with the patient, exon 15 without mutation. The changes of GAA gene exon 15 and 17 in the mother and son were in agreement with that of the patients.Conclusion:(1) Glycogen storage disease type â…¡ can show chronic progressive symmetry of muscle weakness and exercise intolerance. And breathing difficulties also is the initial symptoms of the disease.(2) Skeletal muscle biopsy pathology mainly formed vacuoles within muscle fibers, the morphological diversity, ranging in size with basophilic granules, containing a large number of periodic acid Schiff reaction(PAS) staining positive glycogen. So skeletal muscle biopsy has important value for the diagnosis and differential diagnosis of glycogen storage disease type â…¡.(3) In patients with biochemical detection, the muscle enzyme increased, and the activity of GAA decreased.(4) Gene detection is further confirmed by the mutation of GAA gene caused by the disease, is an important criterion for glycogen storage disease type â…¡ diagnosis, can further do genetic counseling, prenatal diagnosis.