RESUMO
PURPOSE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is more prevalent in some founder populations, but relatively unexplored in Canada. This study aimed at investigating the French-Canadian patients through phenotypic and genotypic characterization. METHOD: Phenotype and demographic characterization were done for 12 affected individuals belonging to eight unrelated families. Samples from 11 cases were analyzed in a molecular clinical laboratory, and muscle biopsies were reviewed for two individuals with a limb-girdle muscle dystrophy. RESULTS: The clinical phenotype was similar to that observed in European Caucasian populations but differed in the non-endocrine spectrum from the American-reported series of cases. Two cases exhibited a limb-girdle muscle dystrophy, and we found preliminary evidence of a mitochondrial dysfunction, since all three biopsies examined showed COX-deficient fibers in excess of what would be expected for age. Electron microscopy showed mitochondrial accumulation without abnormal cristea or inclusions. The c.1616C > T variant in the AIRE gene was responsible for 100% of APECED cases in the French-Canadian population of Saguenay-Lac-Saint-Jean in Quebec, Canada. CONCLUSIONS: We report the first series of French-Canadian cases affected with APECED. The Saguenay-Lac-Saint-Jean region was uncovered as a new founder population for this condition. Muscle biopsy findings expanded the range of previously described APECED-related myopathology. Long term follow-up of our genetically homogeneous French-Canadian cases may help determine if the c.1616C > T variant increases the risk of muscle involvement. A neonatal screening program is under consideration to prevent undesired life-threatening endocrine manifestations.
Assuntos
Poliendocrinopatias Autoimunes , Canadá/epidemiologia , Genótipo , Humanos , Mutação , Fenótipo , Poliendocrinopatias Autoimunes/genéticaRESUMO
Background and aims Chronic pain is affecting a growing number of individuals including adolescents. Different endogenous pain inhibitory systems could confer protection against development of chronic pain. Decreased pain perception can be observed following intense pain (i.e. conditioned pain modulation - CPM) or after physical exercise (i.e. exercise-induced analgesia - EIA). Reduced effectiveness of pain inhibitory mechanisms have been reported in several chronic pain conditions. However, the extent of these dysfunctions has not been thoroughly investigated in adolescents suffering from chronic pain. Our hypothesis was that adolescents suffering from chronic pain have less effective CPM and EIA than pain-free teenagers. Methods Twenty-five healthy adolescent girls and 16 teenage girls with chronic pain participated in this study. Only girls were included in this investigation, since chronic pain is more prevalent in females. The effectiveness of CPM was assessed by comparing heat pain stimulations (individually adapted to induce mild pain intensity) performed with a thermode before and after a cold pressor test (CPT; 2 min, 10 °C). EIA was evaluated by comparing pain intensity produced by an ice cube placed on the forearm before and after a graded exercise test on a cycle ergometer. Results Pain intensity produced by heat pain stimulations decreased following CPT in healthy (p<0.05), but not in chronic pain adolescent girls (p=0.4). Pain intensity induced by the ice cube was reduced after exercise in healthy (p<0.05), but not in chronic pain adolescents (p=0.9). The effectiveness of CPM and EIA was inferior in teenage girls suffering from chronic pain compared to healthy participants (p<0.05). Conclusions Endogenous pain inhibitory mechanisms triggered by intense pain or by physical exercise are effective in healthy adolescent girls. Teenage girls living with chronic pain do not show diminished pain perception after a CPT or a graded exercise test. These results suggest that pain inhibitory mechanisms such as CPM and EIA are ineffective in adolescent girls suffering from chronic pain. Implications In a wider context, the findings of the present research could help understand better the mechanisms involved in the development of chronic pain. Improved comprehension of this subject might help prevent chronic pain conditions and thus, reduce the negative impacts of this burden.