Glycogen storage diseases are a group of rare inborn errors of carbohydrate metabolism. Our research focuses on the elucidation of pathophysiological mechanisms in cell models as well as the impact of hepatic glycogen storage disorders on the life of affected patients.

Glycogen storage diseases (GSDs) are a group of inborn errors of metabolism that result from defects in any of the enzymes involved either in glycogen synthesis or glycogen degradation. GSDs can be divided in two major entities: GSDs with hepatic involvement that usually present with hypoglycemia and often hepatomegaly and muscle GSDs with predominantly neuromuscular symptoms such as muscle weakness and/or hypotonia.

Our research focuses on hepatic storage diseases including type I, and the so-called ketotic GSDs, type III, VI, IX, XI and 0, and our projects comprise basic research projects as well as clinical and translational studies. We apply metabolomic methods to investigate effects of defective glycogen degradation on metabolic networks. Clinical studies aim at a better understanding of the long-term complications of GSDs and the impact of these chronic diseases on the everyday life of affected patients.

We work in close cooperation with the German patient organisation for glycogen storage diseases (SHG Glykogenose Deutschland e.V.).

It has recently been shown in cell and animal models that GSD I is associated with mitochondrial dysfunction. In this project we investigate the energy metabolism of fibroblasts of GSD Ia, Ib, III and healthy controls studying

• mitochondrial organization in live cells by spinning-disc confocal microscopy (mitochondrial content, network morphology)
• oxygen consumption rates
• extra- and intracellular metabolites by targeted LC-MS/MS (metabolomics)

Patients with GSDs have to stick to a special diet which poses them at risk of vitamin B12 deficiency. On the other hand, liver damage has been described as cause of elevated vitamin B12 concentrations in blood.

This study is the first comprehensive assessment of the vitamin B12 metabolism in hepatic GSD patients.

The aims of this study are

1. to assess the vitamin B₁₂ status of patients with hepatic GSDs using different plasma biomarkers of vitamin B₁₂ status, thereby excluding functional deficiency
2. to elucidate whether associations exist between vitamin B₁₂ status and liver function/metabolic control, and
3. to elucidate which other factors (supplementation, age etc.) influence vitamin B₁₂ levels in this patient cohort.

GSD Ia is clinically characterised by severe fasting hypoglycemia, hepatomegaly, failure to thrive, growth retardation, truncal obesity, doll-like facies, short stature, bleeding tendency and hypotrophic muscles. Laboratory findings include hyperuricemia, hyperlipidemia, and elevated lactate levels. GSD Ib shares these main features with GSD Ia, but is additionally aggravated by neutropenia and neutrophil dysfunction, associated with frequent infections and possible chronic inflammatory bowel disease. As patients with GSDs I have to adhere to a strict diet (frequent meals, supplementation of uncooked cornstarch or continuous overnight tube feeds) and have to live with the risk of severe hypoglycaemia, these diseases have a high impact on daily life of patients. Due to improved therapy most patients with GSD I nowadays reach adulthood. As a consequence, they have to deal with new issues of their disease connected with adult daily life such as integration in work and social life, sports, travelling, dietary management, disease monitoring, self-autonomy, family planning, and the patients’ attitude towards their disease.

In this project we investigate the impact of GSD I on adult life in patients from different metabolic centres throughout Germany.