Egyptian glycogen storage disease type III – identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId

摘要

Background: Glycogen storage disease type III (GSD III) is caused by mutations in AGL which encodes for a single protein with two enzyme activities: oligo-1, 4-1, 4-glucantransferase (transferase) and amylo-1, 6-glucosidase. Activity of both enzymes is lost in most patients with GSD III, but in the very rare subtype IIId, transferase activity is deficient. Since the spectrum of AGL mutations is dependent on the ethnic group, we investigated the clinical and molecular characteristics in Egyptian patients with GSD III. Methods: Clinical features were examined in five Egyptian patients. AGL was sequenced and AGL haplotypes were determined. Results: Six novel AGL mutations were identified: a large deletion (c.3481–3588+1417del1525 bp), two insertions (c.1389insG and c.2368insA), two small deletions (c.2223–2224delGT and c.4041delT), and a missense mutation (p.L620P). p.L620P was found in a patient with IIId. Each mutation was located on a different AGL haplotype. Conclusions: Our results suggest that there is allelic and phenotypic heterogeneity of GSD III in Egypt. This is the second description of a large deletion in AGL. p.L620P is the second mutation found in GSD IIId. Clin Chem Lab Med 2009;47:1233–8.