Toward understanding tissue-specific symptoms in dolichol-phosphate-mannose synthesis disorders; insight from DPM3-CDG.

The congenital disorders of glycosylation (CDG) are inborn errors of metabolism with a great genetic heterogeneity. Most CDG are caused by defects in the N-glycan biosynthesis, leading to multisystem phenotypes. However, the occurrence of tissue-restricted clinical symptoms in the various defects in dolichol-phosphate-mannose (DPM) synthesis remains unexplained. To deepen our understanding of the tissue-specific characteristics of defects in the DPM synthesis pathway, we investigated N-glycosylation and O-mannosylation in skeletal muscle of three DPM3-CDG patients presenting with muscle dystrophy and hypo-N-glycosylation of serum transferrin in only two of them. In the three patients, O-mannosylation of alpha-dystroglycan (αDG) was strongly reduced and western blot analysis of beta-dystroglycan (ßDG) N-glycosylation revealed a consistent lack of one N-glycan in skeletal muscle. Recently, defective N-glycosylation of ßDG has been reported in patients with mutations in guanosine-diphosphate-mannose pyrophosphorylase B (GMPPB). Thus, we suggest that aberrant O-glycosylation of αDG and N-glycosylation of ßDG in skeletal muscle is indicative of a defect in the DPM synthesis pathway. Further studies should address to what extent hypo-N-glycosylation of ßDG or other skeletal muscle proteins contribute to the phenotype of patients with defects in DPM synthesis. Our findings contribute to our understanding of the tissue-restricted phenotype of DPM3-CDG and other defects in the DPM synthesis pathway.

Comparing health-related quality of life of cancer patients under chemotherapy and of their caregivers.

INTRODUCTION: Cancer is a major disorder physically and psychologically affecting both patients and their caregivers. In this study, health-related quality of life (HRQoL) of patient-caregiver dyads during the period of chemotherapy was assessed. MATERIAL AND METHODS: Two hundred twenty-two cancer patient-caregiver dyads were enrolled in the study, which was conducted from October 2008 to March 2009. HRQoL was evaluated with EQ-5D. RESULTS: The mean age of the sample was 57.4 and 48.9 for patients and caregivers, respectively. The EQ-5D descriptive system indicates that female patients more frequently experience anxiety and depression than male patients. Male and higher-education caregivers had higher VAS scores, while demographic factors did not seem to influence patients' HRQoL. Anxiety and depression of caregivers were correlated with patients' problems in self-care and usual activities. CONCLUSIONS: Quality of life is highly influenced during the period of chemotherapy for both patients and caregivers and is often under reported. Interventions that can improve HRQoL, especially in the domain of mental health for both cancer patients and their caregivers, need to be implemented.