Insights into genetic and clinical profiles of triple A syndrome in Sudanese children.

Introduction: Triple A syndrome (OMIM*231550) is a rare autosomal recessive disorder characterized by achalasia, alacrima, adrenal insufficiency, and neurological features. It is caused by functional impairment of the nucleoporin ALADIN due to mutations in the Methods: The clinical diagnoses were based on characteristic clinical and laboratory findings. Genetic testing was conducted in 20 families, encompassing 31 patients, revealing six different Results: A previously described mutation in exon 9 (c.934C>T) was present in 35%, and the known Arabic founder mutation c.1331+1G>A (intron 14) was found in 30% of the families. In addition, two novel mutations, including an 8 bp-deletion at the exon 4/intron 4 junction (c.394_399+2delCTGTCTGT) and a 1 bp-deletion in exon 9 (c.852delG) were identified. Discussion: Genotype-phenotype analyses highlighted significant variability in symptom occurrence, age of onset, and disease severity. Consistent with the high consanguinity rates in Sudan, most mutations (95%) occurred in a homozygous state. In conclusion, triple A syndrome is likely underdiagnosed in Sudan and exhibits significant variability in phenotypic presentation even among affected individuals within the same family or mutation.