Glycogen storage disease type VI: clinical course and molecular background.

Glycogen storage disease type VI (GSD-VI; also known as Hers disease, liver phosphorylase deficiency) is caused by mutations in the gene coding for glycogen phosphorylase (PYGL) leading to a defect in the degradation of glycogen. Since there are only about 40 patients described in literature, our knowledge about the course of the disease is limited. In order to evaluate the long-term outcome of patients with GSD-VI, an observational retrospective case study of six patients was performed at the University Children's Hospital Zurich. The introduction of small, frequent meals as well as cornstarch has led to normal growth in all patients and to normalization of liver transaminases in most patients. After starting the dietary regimen, there were no signs of hypoglycemia. However, three of six patients showed persistent elevation of triglycerides. Further, we identified four novel pathogenic PYGL mutations and describe here their highly variable impact on phosphorylase function.Conclusions: After establishing the diagnosis, dietary treatment led to metabolic stability and to prevention of hypoglycemia. Molecular genetics added important information for the understanding of the clinical variability in this disease. While outcome was overall excellent in all patients, half of the patients showed persistent hypertriglyceridemia even after initiating treatment.What is Known:• Glycogen storage disease type VI (GSD-VI) is a metabolic disorder causing a defect in glycogen degradation. Dietary treatment normally leads to metabolic stability and prevention of hypoglycemia.• However, our knowledge about the natural course of patients with GSD-VI is limited.What is New:• While outcome was overall excellent in all patients, half of the patients showed persistent hypertriglyceridemia even after initiating treatment.• Molecular genetics added important information for the understanding of the clinical variability in this disease.

Safety and Efficacy of Bilateral Epiphysiodesis Surgery to Reduce Final Height in Extremely Tall Adolescents - A Follow-up Study.

INTRODUCTION: Treatment options in patients with extreme tall stature are limited. Bilateral epiphysiodesis has emerged as a possible treatment method aiming to reduce final height. However, there is still insufficient data on long-term safety and final height outcome. Therefore, the aim of this study was to assess the efficacy and safety of bilateral epiphysiodesis to reduce final adult height in tall adolescents. METHODS: The study population consisted of 72 patients with extreme tall stature who were followed at the Pediatric Endocrine Clinic at the Karolinska University Hospital, Stockholm (Sweden) and subsequently underwent bilateral epiphysiodesis around the knees (girls n=45, boys n=27). RESULTS: When compared to the final height prediction at time of surgery, the procedure significantly reduced the achieved final height by a mean of 3.6 cm ± 0.4 cm in girls (p<0.001; 26.0 ± 2.9 % reduction) and 8.6 ± 0.9 cm in boys (p<0.001; 40.5 ± 3.0 % reduction). Furthermore, a negative correlation was observed between the absolute height reduction and the bone age at time of surgery, which was stronger in boys (r=-0.63, p<0.001) than in girls (r=-0.44, p<0.001). Besides reducing final height, body proportions were affected in all patients subjected to bilateral epihyseodesis. However, as tall individuals typically have relatively long legs, body proportions were rather normalized after the surgery. There were no serious complications reported. CONCLUSION: This study suggests that bilateral epiphysiodesis is an efficient and safe method to reduce final height in extremely tall adolescent girls and boys. The achieved height reduction was higher in boys and when performed at an earlier bone age. Importantly, no serious side-effects were reported. However, a continued follow-up is still warranted to detect any potential rare complications.