Clinical And Genetic Characteristics Of11Patients Of Glycogen Storage Disease Type â…¨a

ObjectivesGlycogen storage disease type IX （GSD type IX） is one of the most common types of glycogen storage disease accounting for about25%of all patients and is caused by a defect of phosphorylase kinase （PhK）. Glycogen storage disease type â…¨a formerly known as X-linked liver glycogenosis （XLG） results from lacking of liver-a subunit and accounts for about75%of all the GSD type â…¨cases.Until now about103patients have been detected but none of them is chinese, clinical symptoms of patients with XLG included Clinal symptoms of type IX a include growth retardation, hepatomegaly, and these clinical and biochemical manifestations improved even disappeared with age. In this study, based on the gene sequencing of25patients suspected GSD type â…¨a, we tried to establish diagnosis method, summarize the clinical and genetic characteristics and discuss the relationship between phenotype and genotype of GSD type â…¨a.MethodsDNA was extracted from peripheral blood then PHKA2gene sequencing was performed. The sequence was checked from UCSC-Genomes （NM₀00292）, and the pathogenicity of the frst reported missense mutations was predicted by SIFT and PolyPhen softwares. We collected clinical data of admitted to hospital and every follow-up to analyze clinical and genetic characteristics of our patients.ResultsThe11patients came from10unrelated families of unconsanguineous couples, and1patient had positive fmily history. Age of onset ranged from3months old to6years old and the median age was1-year old. The chief complains included hepatomegaly （10/11）, liver disfunction （4/10）, growth retardation （2/10）, frequent hunger （1/10） and anemia （1/10）.The physical examinations, biochemical findings and abdominal ultrasound showed liver enlargement among10patients, liver disfunction in9patients, growth retardation in5patients, blood lipids elevated in3patients and hypoglycaemia in2patients.During the subsequente follow-up, clinical and biochemical manifestations of the patients improved even disappeared with age. In addition,2adult patients had normal final height, and this was consistent with literature that final height of patients with this disease tended to be normal.5of11patients stopped taking cornstarch with the median age of13.5years old but the clinical and laboratory results were satisfactory. Considering the genotype and phenotype among patitents that we evaluated, it seems that there was not relationship between genotype and phenotype of this diease.After PHKA2gene sequencing, we found7missense mutations of8patients,1nonsense mutation of c.1498CT p.Arg45Ter in1patient,1micdeletion mutation of c.2726₂727delTT p.Phe909Cys fs31x in1child, and1splicing mutation of c.237+1G>T in1child. The mathers were the carrier of the mutations.The7missense mutations included （1） C-to-T transition at nucleotide position133, changing the arginine at amino acids45to tryptophan （c.133CT p.Arg45Trp）;（2） A-to-G transition at nucleotide position338, changing the histidine at amino acids113to arginine （c.338A>G p.His113Arg）;（3） G-to-A transition at nucleotide position392, changing the glycine at amino acids131to aspartic acid （c.392G>Ap.Gly131Asp）;（4） A-to-T transition at nucleotide position407, changing the aspartic acid at amino acids136to valine （c.407A>T p.Asp136Val）;（5） G-to-A transition at nucleotide position884, changing the arginine at amino acids295to histidine （c.884G>Ap.Arg295His）;（6） G-to-A transition at nucleotide position899, changing the glycine at amino acids300to arginine （c.899G>A p.Gly300Asp）;（7） G-to-A transition at nucleotide position2746, changing the arginine at amino acids916to tryptophan （c.2746G>A p.Arg916Trp）.ConclusionsGlycogen storage diseade type â…¨ a is a mild disorder with a favorite prognosis and do not affect kidney and skeletal muscle which is different from other types of GSD. Althouth our sample size was limited, there are features to query whether serious treatment was essentil for older patients with glycogen storage disease type â…¨a or not.