Clinical Diagnosis And Genetic Analysis Of A Child With Fructose-1,6-bisphosphatase Deficiency

Objective To review and summarize the clinical characteristics and diagnosis of child with repeatedly severe metabolic acidosis and hypoglycemia,and to explore the target gene test for diagnosisinherited metabolic disorders.Methods 1.Subjects A child diagnosed with fructose-1,6-bisphosphatase deficiency(FBPase)in the Affiliated Hospital of Q ingdao University and members of her family.2.Methods:(1)The clinical data including of manifestations,laboratory tests,metabolites assay in blood and urine was analyzed retrospectively.(2)C haracteristics of this case were summarized.The very distinctive trait was snatched and as keyword to search literatures in Pub Med.We compared the disease that we got with the characteristics of our cases.(3)Genomic DNA was extracted from peripheral blood leukocytes of the proband,her parents and sister.All coding exons and proximal splice sites of the FBP1 gene were amplified by PC R with FBP1-specific primers for the proband.(4)The protein functions of mutations were predicted by SIFT and Polyphen-2.Results A 6-year-old girl characterized by recurrent episodes of severe hypoglycemia,lactic acidosis after different precipitating factors.She showed normal face,normal mental and psychomotive development and hepatomegaly.On evaluation,she had hypoglycaemia with acidosis,and urine ketonuria and glyceroluria.Glyceroluria was a very distinctive trait.We searched literatures with glyceroluria as keyword in Pub Med.Three related diseases were identified: FBPase deficiency,glycerol kinase(GK)deficiency and complex GK deficiency.Further reading of related literatures to understand the characteristics of diseases and laboratory tests,GK deficiency is X-linked recessiveinheritance,the common clinical manifestation was fasting hypoglycemia,hypertriglyceridemia and Reye,s syndrome.Complex GK deficiency is Xp21 contiguous gene syndrome also with X-linked recessive inheritance,which leads to adrenal hypoplasia congenital,GK deficiency and muscular dystrophy.The proband was female and did not have manifestations like those two diseases,so GK deficiency and complex GK deficiency were excluded.The mutation analysis of FBPase gene(FBP1)was performed by Sanger sequencing and discovered a novel compound heterozygous mutations of c.355G>A and c.960 del G.Her father and sister was c.355G>A heterozygote,and her mother was c.960 del G heterozygote,respectively.The protein functions predicted by SIFT and Polyphen-2 was damaged.Conclusions 1.A 6-year-old girl characterized by recurrent episodes of severe hypoglycemia,lactic acidosis after different precipitating factors.Glyceroluria was a very distinctive trait.We searched literatures in Pub Med with glyceroluria as keyword,and preliminary diagnosed FBPase deficiency.The mutation analysis of FBPase gene(FBP1)was performed.2.Full analysis of disease-related traits and targeted gene testing is one of the effective methods for accurate diagnosis of inherited metabolic disorders.3.New mutations of c.355G>A and c.960 del G further expand the spectrum of genotype and phenotype in FBP deficiency.