Debranching enzyme is encoded by 85-kb AGL gene on chromosome 1p21. Six transcript isoforms have been isolated, alternatively spliced in 5’ of the gene: the main of them, isoform 1, is ubiquitous and is about 7.0 kb long. A large genetic screening led to the observation that GSDIIIb patients had mutations in exon 3 (7), whereas GSDIIIa arose with downstream mutations. At present, a formal demonstration of this is

still lacking. Clinical data We reviewed clinical, biochemical and genetic data of 51 patients (26 males and 25 females) with GSD III from Centers throughout Italy. All had absent or severely reduced Inhibitors,research,lifescience,medical debranchig enzyme activity, either on red blood cells or muscle tissue. Median age of patients was 25.8 years (range: 2-75). Liver damage and structure were monitored over the entire Inhibitors,research,lifescience,medical lifetime of these patients: we observed an inverse correlation between aspartate and alanine amino transferase (AST, ALT) levels and age, with high transaminase levels in the first decade and in particular in the first three years of age and a progressive reduction in adulthood. Liver echography

was useful to differentiate patients with mild or severe Inhibitors,research,lifescience,medical liver involvement. We considered four degrees of liver involvement as evaluated by echocardiography: a) normal; b) patients with mild hepatomegaly and diffuse homogeneous hyperechogenicity, classified as having mild liver disease; c) patients with hepatomegaly and inhomogeneous hyperechogenicity classified in the moderate liver disease group; d) hepatic involution, cirrhosis or liver transplant were considered indicators of severe liver disease. Among 44 patients we found 2% with normal liver echography, 78% with Inhibitors,research,lifescience,medical mild, 16% with moderate and 4% with severe liver disease. In the first decade most patients (86%) showed mild liver disease, while only 5% of patients showed normal liver

echography; 9% of patients had moderate hepatic involvement. In the second decade 100% of patients had signs of mild liver disease. In the third decade 66.6%, 16% and 16% of patients presented respectively mild, moderate and Inhibitors,research,lifescience,medical severe hepatic involvement, while none had normal liver imaging. In patients aged over 30 years, none had normal liver findings, 55%, 36% and 9% of this age group had respectively mild, moderate and severe liver disease. Only two patients BIX 01294 chemical structure developed liver failure and needed liver transplantation at 23 and 32 years of age respectively. Muscular weakness and GSK458 datasheet disability were evaluated using a modified Walton Functional Rating Scale (8), to take into consideration signs of distal lower limb weakness. We observed a direct correlation between age and disease progression, with higher functional rating scores in older patients. Functional impairment is very mild in patients younger than 35 years, who mainly have scores lower than 2. Older patients present a higher variability of the functional score, ranging from 3 to 10.