Background-Anemia in patients with Crohn's disease (CD) is a common problem of multifactorial origin, including blood loss, mal-absorption of iron, and anemia of inflammation. Anemia of inflammation is caused by the effects of inflammatory cytokines [predominantly interleukin-6 (IL-6)] on iron transport in enterocytes and macrophages. We sought to elucidate alterations in iron absorption in pediatric patients with active and inactive CD.

The glycogen storage diseases comprise several inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. In contrast to the classic hepatic glycogen storage diseases that are characterized by fasting hypoglycemia and hepatomegaly, the liver is not enlarged in GSD0. Patients with GSD0 typically have fasting ketotic hypoglycemia without prominent muscle symptoms. Most children are cognitively and developmentally normal. Short stature and osteopenia are common features, but other long-term complications, common in other types of GSD, have not been reported in GSD0. Until recently, the definitive diagnosis of GSD0 depended on the demonstration of decreased hepatic glycogen on a liver biopsy. The need for an invasive procedure may be one reason that this condition has been infrequently diagnosed. Mutation analysis of the GYS2 gene (12p12.2) is a non-invasive method for making this diagnosis in patients suspected to have this disorder. This mini-review discusses the pathophysiology of this disorder, use of mutation analysis to diagnose GSD0, and the clinical characteristics of all reported cases of GSD0.

Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-a. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/ 8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver.