A deficiency in G6PT causes glycogen storage disease type Ib, an autosomal recessive disorder characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction.
Inactivation of either G6PT or G6Pase-β increases neutrophil apoptosis, which underlies, at least in part, neutrophil loss (neutropenia) and dysfunction in GSD-Ib and G6Pase-β deficiency.
Glycogen storage disease type I (GSD-I) is a kind of human genetic disorders and is caused by the deficiency of a microsomal protein, glucose-6-phosphatase-α (G6Pase-α) or glucose-6-phosphate transporter (G6PT) responsible for glucose homeostasis, leading to GSD-Ia or GSD-Ib, respectively.
Neutropenia had been observed since 6 months of age, but the diagnosis of GSD Ib was established only at 18 months of age two mutations (c.354_355insC (p. W118fsX12) and c.736T>C (p.W246R)) were detected on his SLC37A4 gene.
Glycogen storage disease type Ib is caused by deficiencies in the glucose-6-phosphate transporter (G6PT), a phosphate (P(i))-linked antiporter capable of homologous (P(i):P(i)) and heterologous (G6P:P(i)) exchanges similar to the bacterial hexose-6-phosphate transporter, UhpT.
We infused neonatal GSD-Ib mice with adeno-associated virus (AAV) carrying G6PT and examined their metabolic and myeloid phenotypes for the 72-week study.
Neutropenia had been observed since 6 months of age, but the diagnosis of GSD Ib was established only at 18 months of age two mutations (c.354_355insC (p. W118fsX12) and c.736T>C (p.W246R)) were detected on his SLC37A4 gene.
The glucose-6-phosphate transporter (G6PT) deficient in glycogen storage disease type Ib is a phosphate (P(i))-linked antiporter capable of G6P: P(i) and P(i):P(i) exchanges.
To evaluate the feasibility of gene replacement therapy for GSD-Ib, we have infused adenoviral (Ad) vector containing human G6PT (Ad-hG6PT) into G6PT-deficient (G6PT(-/-)) mice that manifest symptoms characteristics of the human disorder.