Clinical and molecular genetic findings in a 6-year-old Bosnian boy with triple A syndrome.
The triple A syndrome is a rare autosomal recessive disease that is characterised by the triad of adrenocorticotropin (ACTH)-resistant adrenal insufficiency, achalasia and alacrima. In most patients, neurological and dermatological abnormalities are associated features. We report on the first Bosnian patient with triple A syndrome. Endocrine investigation confirmed primary adrenal insufficiency at the age of 5.8 years. Two months later, achalasia was diagnosed, and in the presence of alacrima, the patient satisfies the diagnostic criteria of triple A syndrome. In addition, a large number of associated neurological and dermatological features were present in this patient. Moreover, he has dysmorphic facial features, which have not been previously described in triple A syndrome. Triple A syndrome was confirmed by molecular analysis, revealing a nonsense mutation p.W84X in the AAAS gene. The parents are both heterozygous carriers of the mutation. The affected twin brother unfortunately died from hypoglycaemic shock, despite a normal cortisol rise in an ACTH stimulation test. Further, triple A syndrome patients carrying the identical homozygous p.W84X mutation have to be studied to assess a genotype-phenotype relationship for this mutation.
Toromanovic
Alma
A
Department of Pediatrics, University Clinical Center, Trnovac bb, 75000, Tuzla, Bosnia and Herzegovina. almatoromanovic@bih.net.ba
Tahirovic
Husref
H
Milenkovic
Tatjana
T
Koehler
Katrin
K
Kind
Barbara
B
Zdravkovic
Dragan
D
Hasanhodzic
Mensuda
M
Huebner
Angela
A
D000224:Addison Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D002404:Catheterization; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004931:Esophageal Achalasia / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D017809:Fatal Outcome; D005838:Genotype; D006720:Homozygote; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007766:Lacrimal Apparatus Diseases / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome; D014427:Twins
C416506:AAAS protein, human; D018389:Codon, Nonsense; D006728:Hormones; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D006854:Hydrocortisone