Bao and Nambu

independently VRT752271 solubility dmso reported two infants with neonatal hypotonia and dilated cardiomyopathy, who died in the first months of life (17, 19). They harboured a splice-site mutation leading to exon skipping in the first case, and a homozygous single-nucleotide deletion in the second (17, 19). Two other cases presented with severe neonatal hypotonia and died within 40 days of life: the first had two single-base pair deletions and the second had a large homozygous deletion encompassing exons 8 to 12 (6). We reported three additional patients (two of them siblings) Inhibitors,research,lifescience,medical with decreased fetal movements and polyhydramnios, severe hypotonia at birth requiring mechanical ventilation, who died at ages ranging from 4 weeks to 4 months. The two siblings showed a nonsense mutation and a large deletion, while the third patient was a compound heterozygote for a nonsense mutation and a missense mutation in a highly conserved Inhibitors,research,lifescience,medical amino acid (7). Decreased

fetal movements, polyhydramnios, severe hypotonia with respiratory insufficiency requiring ventilatory support, also characterized the clinical presentation of a baby-girl, who died at 2 months of age (20). Inhibitors,research,lifescience,medical Recently, Burrow and collegues reported a child with non-lethal congenital hypotonia without hepatic or cardiac involvement, due to GSD-IV. Genetic analysis revealed the presence of two missense utations in the GBE1 gene (14). Adult polyglucosan body disease Adult polyglucosan body disease (APBD, MIM 263570) is a clinical variant of GBE deficiency. It is a late-onset neurological disease clinically characterized

by progressive upper Inhibitors,research,lifescience,medical and lower motor neuron involvement, sensory loss, early urinary incontinence, and dementia in about half of the patients (12, 13). Polyglucosan bodies accumulate in the axons and hillocks of Inhibitors,research,lifescience,medical neurons in both gray and white matter, at difference from the polyglucosan bodies of Lafora disease, which are never seen in neuronal perikarya. To date, genetic analysis of the GBE1 gene identified an homozygous missense mutation – c.986A > C (p.Y329S) – in several Ashkenazi Jewish patients (21). Ubogu and collegues during reported a manifesting heterozygous patient with 48% of GBE activity and a single common Ashkenazi-Jewish Y329S mutation (22). Ziemssen and collegues identified two heterozigous mutations in a non-Jewish patients with reduced GBE activity (c.1544G > A p.R515H.1571G > A p.R524Q) (23). Prenatal diagnosis Prenatal diagnosis can be performed by the measurement of the GBE activity in cultured chorionic villi cells and in cultured amniotic fluid cells (24), or by DNA analysis in genetically confirmed cases (25). Animal models Two naturally occurring animal models with GSD-IV are known, the Norwegian Forest cat and the American Quarter horse. In Norwegian Forest cats, the disease is fatal and affects primarily the striated muscles and the nervous system. A 6.