They ranged from 29 to 3097 I.U. with a mean value of 899 in the first decade, from 57 to 6574 (mean: 2763 I.U.) in the second decade, from 87 to 3422 in the third decade (mean: 1047 I.U.). Older patients showed a decrease of CK values probably due to progressive muscle loss. Signs and symptoms of heart function were also evaluated: 45% of patients Inhibitors,research,lifescience,medical had normal echographic findings, 54% had mild Paclitaxel in vivo hypertrophy and 1% had moderate hypertrophy. None of the patient in our group had severe cardiac hypertrophy. Molecular data AGL gene was analyzed by direct sequence of the

coding region and splicing sites. 35 patients could be completely characterized (69%), whereas only one allele was identified in 7 patients Inhibitors,research,lifescience,medical (14%), while 9 patients (17%) resulted negative. The majority of changes are represented by mutations giving rise to null alleles. The IVS21 + 1G/A intronic change is the most frequent mutation in our series (23.4%). Missense mutations amount to 25% of total. Identified mutations are widespread along the whole gene and no particular hot spot could be found. Grouping mutation type by severity (null vs. missense) and gathering clinical and Inhibitors,research,lifescience,medical genetic data, it came out that null patients have higher probability to develop more severe myopathic and hepatic involvements. Anyway, exceptions in both directions exist. Furthermore,

as with other genetic diseases, Inhibitors,research,lifescience,medical the difficulty in establishing genotype-phenotype correlations is something well known with GSDIII. IVS21 + 1G/A is a good example in this sense (9). Among our patients, we observed the case of three genotypically identical adult patients, which were homozygous for the exon 21 skipping. All of them developed a severe myopathy, and hepatopathy, though at quite different ages and degree, but only the older of them suffers Inhibitors,research,lifescience,medical from cardiopathy. A further complication comes from the presence of intrafamilial clinical variability. As far as different types of GSDIII are concerned, all our informative patients (those older than 30: n = 19) are affected by GSD type IIIa. Genetic screening on ethnically different populations

has shown that only very few mutations are common in a considered geographic area, the great majority being private mutations. The only mutation shared Terminal deoxynucleotidyl transferase by Caucasians coming from different countries is R864X, identified in Mediterranean and North American population. The mutation IVS6 + 3 A/G accounts for 11.7% of mutated alleles in Mediterranean families (10). Therapy and perspectives Therapy is not available for debranching enzyme deficit. To avoid fasting hypoglycaemia in infancy, dietary measures have been prospected. Frequent daytime high-protein feedings (45% carbohydrate, 25% protein, 30% fat) and supplementation of uncooked corn starch before sleep showed to be effective in young patients with regard to metabolic control and growth retardation.