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Glycogen Storage Disease type VI and IX; additional recommendations for follow-up and treatment beyond childhood

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  • Biology
  • Chemistry
  • History
  • Medicine


Background: Glycogen storage diseases (GSD) are inherited disorders primarily affecting the liver or muscle. There are different types of hepatic GSDs, of which type VI and IX are assumed to be the mildest forms. GSD VI and IX are caused by deficiency of the enzymes phosphorylase and phosphorylase b-kinase, respectively. The reduced ability to mobilize glucose from glycogen in the liver results in fasting hypoglycemia, hepatomegaly, growth retardation and biochemical abnormalities. There is a high variability in clinical phenotype and little is known about the long term complications. The goal of this study is to identify the frequency of long-term clinical problems and to provide guidelines for the long-term follow-up during the disease course. Moreover, in the absence of an X-linked inheritance pattern, differentiation between both types of GSD is complicated by indistinguishable clinical symptoms. DNA-analysis is necessary to establish accurate diagnosis. To provide optimal care in older patients and enable genetic counseling for patients and their families, this study describes the natural course of patients with GSD VI and IX. Methods: At first a retrospective analysis of clinical features during follow-up was performed. This was followed by a cross sectional study including full medical history, physical examination, biochemical analysis, abdominal ultrasound and bone density measurement of 20 patients from 14 families with GSD VI and IX. In 16 patients DNA-analysis was initiated. Results Clinical features including hepatomegaly, hypoglycemic events, growth retardation and motor developmental delay, were most pronounced during childhood. There is a strong correlation between hepatomegaly and age. Biochemical findings displayed elevated concentrations of TSH (25%), liver transaminases (25%), triglycerides (30%) and uric acid (35%) and decreased concentrations of vitamin D (45%). The use of XO-inhibitors appeared to be beneficial in patients with hyperuricemia. In two patients focal lesions in the liver were detected during abdominal ultrasound and seven out of 20 (41%) patients were diagnosed with osteopenia or osteoporosis based on results of DEXA-scanning. Nine out of 20 patients carry one founder mutation in the PHKA2 gene (c.3614 C>T) causing X-linked hepatic GSD IX. Conclusion: Our study confirmed that the majority of clinical signs seem to improve with age. However, based on several findings, we advocate the annual follow-up of biochemical parameters, including 25(OH)D, in adult patients. Additional evaluation of thyroid function depends on clinical symptoms and serum concentrations of TSH and FT4. Hyperuricemia should be treated with XO-inhibitors. Furthermore, as we found that focal lesions in the liver are a long term complication in these patients as well, we advise the use of abdominal ultrasound to detect patients at risk of hepatic tumor. Moreover, this data presents a surprisingly high incidence of osteopenia and osteoporosis, its cause and treatment require further investigation. We advise to optimize calcium intake and, if indicated, start supplementation of vitamin D at an early age. DEXA scan should be performed every two years to assess BMD status. In addition, DNA analysis is recommended for accurate diagnosis and identifies the pattern of inheritance allowing adequate genetic counseling.

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