Glikojen Depo Hastalığı Nedir

Thesis Type: Post Doctorate of Medicine

Institution Of The Thesis: Gazi &#;niversitesi, Tıp Fak&#;ltesi, Turkey

Approval Date:

Student: F. TUBA EMİNOĞLU

Supervisor: LEYLA TÜMER

Glycogen storage disease type 1 (GSD 1) is a group of conditions with autosomal recessive inheritance resulting in disfunction of GlucosePhosphatase (G6Pase) system which plays a key role in the regulation of blood sugar. In the G6Pase system, deficiency of G6Pase which hydrolyzes G6P to glucose and phosphate in the lumen of endoplasmic reticulum leads to glycogen storage disease type 1a, while deficiency of G6P transporter which transports G6P from cytoplasm to the lumen of endoplasmic reticulum causes glycogen storage disease type 1b. Molecular genetic levels of the proteins, G6Pase and G6PT, were described in G6Pase system. Up to the present, 76 distinct mutations were defined in G6Pase gene, and 73 different mutations were defined in G6PT gene. Particularly in some ethnic groups and geographic regions, allelic homogeneity was detected in GSD 1. In the present study, the most prevalent mutations in the world were searched by microelectronic array technology, a new method, in 27 Turkish patients diagnosed for GSD 1a and 3 with GSD 1b, and the relation between detected mutations and clinical and laboratory findings was investigated. Mutations causing the disease were detected in 45 (%) of 54 alleles screened in the cases with GSD 1a. Allelic frequency of mutations (R83C, GV, GR, W77R) looked for were found as %, %, %, and %, respectively. GR mutation was detected for the first time in a patient of Turkish origin. Eight (RQ, QX, 35X, X, D38V W63X, >T, DelF) of 12 mutations looked for were coincided in none of the patients. The patient with homozygous W77R mutation seemed to present milder clinical and laboratory findings, compared to other patients. GC mutation was detected only in a single allele of two of three patients with the diagnosis of GSD 1b. Allelic frequency of GC mutation was determined as %. Two other mutations (delCT ve WR ) looked for were coincided in none of three patients. In conclusion, we suggest that microarray technology, which allows rapid analysis of frequently detected mutations and has considerably lower costs than other methods, can be successfully used in diagnosis of GSD 1a in populations with allelic homogeneity, such as patients of Turkish origin, instead of screening the whole gene. By expanding the mutational panel in the chip and using complex genetic analysis methods, we may increase the frequency of detecting mutations in much more Turkish GSD1b patients.