Background: Triple A syndrome (alacrima, achalasia, adrenal failure, progressive neurodegenerative disease) is caused by mutations in the AAAS gene which encodes the protein ALADIN. Osteoporosis seems to be an overlooked symptom in triple A syndrome.
Objective and hypotheses: To evaluate etiology of osteoporosis in six male and four female patients with triple A syndrome.
Method: X-ray, dual X-absorptiometry (DXA) of the lumbar spine and hip, bone turnover markers, minerals, ALP, 25-OHD, 1,25-OH2D, PTH and adrenal androgens were measured.
Results: At time of diagnosis osteoporosis was suspected on X-ray in eight of ten patients aged 211 years (DXA was not available) and normal levels of minerals and ALP were measured in ten patients. Seven to 30 years after introduction of 12 mg/m2 per day hydrocortisone (at age 937 years) DXA showed low Z-score −2.1 in two children and osteoporosis in eight adults (T-score between −2.6 and −4). Normal levels of minerals, ALP, PTH, 1,25-OH2D, osteocalcin, crosslaps (CTX), procollagen 1 (P1CP) were found in ten patients. Low levels of DHEAS (0.11 μmol/l, NR 311) and androstenedione (0.21 μmol/l, NR 29) in all and low levels of 25-OHD (1844 μmol/l, NR 50150) were found in six patients. In all patients BMI was <25 ct. for age and sex. Osteoporosis was not associated with sex or the type of the AAAS gene mutation.
Conclusion: Appropriate glucocorticoid replacement probably had no detrimental effects on BMD. Osteoporosis may be the consequence of low levels of adrenal androgens, the neurological impairment causing physical inactivity, inadequate sun exposure and protein malnutrition secondary to achalasia. Regarding ubiquitous ALADIN expression, osteoporosis may be phenotypic feature of the disease. Besides optimizing glucocorticoid dose, physical activity, adequate sun exposure, appropriate nutrition and vitamin D supplementation, therapy with DHEA could be considered.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology