French-Canadian families from Saguenay-Lac-Saint-Jean: a new founder population for APECED.

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.

Use of a vibrating mesh nebulizer for allergen challenge.

BACKGROUND: Allergen inhalation tests are a valuable research tool. The allergen dose producing an early asthmatic response (EAR) can be predicted from methacholine responsiveness and allergen skin test endpoint (STE). The Wright® jet nebulizer, which is both inefficient and increasingly difficult to obtain, has been used historically. We assessed the Solo® vibrating mesh nebulizer as an alternative for allergen and methacholine challenges. METHODS: Eighteen mild atopic asthmatics completed the study. Doubling concentration allergen prick skin tests were performed to determine the STE in allergen units/mL. The Wright® protocol was used to measure the methacholine provocation dose causing a 20% forced expired volume in one second (FEV1) fall (PD20) (µg) and the allergen PD20 (units). The Solo® protocol (0.5 mL nebulized to completion, tidal breathing inhalation) was used to determine both methacholine PD20 and allergen PD20. The nebulizer order was randomized and separated by ≥ 2 weeks. RESULTS: All data were log transformed. The allergen PD20, predicted from the methacholine PD20 and the STE, was within 2 doubling doses of the PD20 measured with the Wright® and 2.64 doubling doses of that measured with Solo®. The Wright® allergen PD20 correlated with the Wright® methacholine PD20 (r = 0.74) and the STE (r = 0.78) and more strongly with the product of the two (Wright® methacholine PD20 × STE, r = 0.91, p < 0.00001). The Solo® allergen PD20 showed similar relationships with the Solo® methacholine PD20 (r = 0.61), the STE (r = 0.75) and the product of the two (Solo® methacholine PD20 × STE, r = 0.83, p < 0.00002). The Wright® and the Solo® methacholine geometric mean PD20s were not significantly different (49.3 and 54.5 µg respectively, p = 0.62). The Wright® allergen PD20 was slightly but significantly lower than the Solo® allergen PD20 (geometric means 6.7 and 10.5 units respectively, p = 0.003). CONCLUSION: The Solo® allergen PD20 showed the same relationship with methacholine responsiveness and STE as did the Wright®. The Solo® allergen PD20 was slightly but significantly higher than the Wright® allergen PD20. The Solo® vibrating mesh nebulizer was well tolerated and is an acceptable alternative for allergen challenge.Trial registration clinicaltrials.gov: NCT03491358.

Spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma associated with primary hypothyroidism.

We report an unusual case of spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma in an adult, non-pregnant woman. Her condition was triggered by unrecognized primary hypothyroidism, which regressed after thyroid hormone replacement therapy. This case highlights the need for clinicians and radiologists to familiarize themselves with the clinical and imaging features detected in case of these complications of primary hypothyroidism, which are not well known in the medical and radiological profession. Such improved knowledge will help avoid delays in diagnosis, progression to life-threatening complications, and unnecessary surgery.