Background: Triple A syndrome (AAAS, OMIM#231550) is a very rare inherited disease characterized by the association of chronic adrenal insufficiency, achalasia, alacrima and central and peripheral neurological disorders. It is caused by mutations in the AAAS gene which encodes the nuclear pore complex scaffolding protein ALADIN. The relative prevalence and genotype of AAAS in the Maghreb countries has not been ascertained.
Objective and hypotheses: To estimate the prevalence, clinical features and genetic findings of triple A syndrome among children with chronic adrenal insufficiency in Algeria.
Method: Clinical data were collected retrospectively from the medical records of patients attending a single center between 2007 and 2014. Written informed consent was obtained from patients and family members for genetic testing.
Results: Of 160 children and adolescents with chronic adrenal insufficiency, 25 (15.6%) were diagnosed with Triple A syndrome, rendering it the second most common cause of chronic adrenal insufficiency after congenital adrenal hyperplasia. The 25 patients (15 males: ten females) were from 20 families, the parents being consanguineous in 17 (68%) cases. There was a family history of unexplained sibling death in seven patients. Mean±SD (range) age at diagnosis was 4.34±2.80 (110.8) years, height at diagnosis (WHO 2007 data) was −1.26±1.5 SDS, BMI 0.74±1.36 SDS. All patients were initially diagnosed because of adrenal insufficiency, 19 with isolated glucocorticoid deficiency, six with combined glucocorticoid and mineralocorticoid deficiency. All patients had alacrima, all but one had achalasia and nine patients had neurological disorders. Genetic analysis of the AAAS gene was performed for seven families. The previously reported IVS14+1G>A splice donor mutation was found in six patients, the EVS9 mutation in one patient.
Conclusion: Although rare, Triple A syndrome is the second most common cause of chronic adrenal insufficiency in our patients as well as being a cause of unexplained death in young undiagnosed children.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology