Normoglycemia alone is insufficient to prevent long-term complications of hepatocellular adenoma in glycogen storage disease type Ib mice

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.

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Clinical Analysis and Long-term Treatment Monitoring of 3 Patients with Glycogen Storage Disease Type Ib

10.21203/rs.3.rs-120608/v1 ◽

2020 ◽

Author(s):

Caiqi Du ◽

Zhuoguang Li ◽

Hong Wei ◽

Min Zhang ◽

Minghui Hu ◽

...

Keyword(s):

Glycogen Storage Disease ◽

Metabolic Disorders ◽

Storage Disease ◽

Liver Enzymes ◽

Glycogen Storage Disease Type ◽

Glycogen Storage ◽

Term Treatment ◽

Disease Type ◽

Long Term Treatment

Abstract Background To investigate the clinical and genetic characteristics of patients with glycogen storage disease type Ib (GSD Ib).Methods Retrospectively analyzed the clinical data of 3 patients with GSD Ib admitted into our hospital, and summarized their onset characteristics, clinical manifestations, related examinations and treatment as well as mutational spectrum.Results After gene sequencing, the diagnosis of GSD Ib was confirmed in all 3 patients. Five variants of SLC37A4 gene were detected, of which c. 572C>T was the common variant and c. 680G>A was a novel variant. The 3 cases of GSD Ib were mainly affected by liver enlargement, growth retardation, etc., and all had a history of repeated infections. At the onset, patients mainly manifested as mildly elevated alanine-aminotransferase (ALT), accompanied by decreased absolute neutrophil count (ANC), hypertriglyceridemia, and metabolic disorders (hypoglycemia, hyperlactic acidemia, metabolic acidosis, etc.). After long-term treatment by oral uncooked cornstarch, the abnormal liver enzymes gradually returned to normal, and metabolic abnormalities were basically controlled most of the time. With increasing age, ANC of the 3 patients decreased progressively, whereas the times of infections was reduced.Conclusions The possibility of GSD type Ib should be kept on alert when a patient suffers recurrent infections, accompanied by hepatomegaly, elevated liver enzymes，hypoglycemia, dyslipidemia, and metabolic disorders. At present, the treatment of GSD Ib is mainly a comprehensive intervention based on diet therapy, and it is necessary to be alert to the occurrence of infectious immune diseases such as inflammatory bowel disease during follow-up.

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