(DOI:10.1159/000161867)
Late-Onset Triple A Syndrome: A Risk of Overlooked or Delayed Diagnosis and ManagementSalmaggi A.a · Zirilli L.b · Pantaleoni C.a · De Joanna G.a · Del Sorbo F.a · Koehler K.c · Krumbholz M.c · Huebner A.c · Rochira V.baIstituto Nazionale Neurologico Carlo Besta, IRCCS, Milan; bChair of Endocrinology, Department of Medicine, Endocrinology and Metabolism, and Geriatrics, University of Modena and Reggio Emilia, Ospedale S. Agostino-Estense di Baggiovara, Modena, Italy; cChildren’s Hospital, Technical University Dresden, Dresden, Germany
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Article / Publication Details
Received: December 07, 2007
Accepted: February 28, 2008
Published online: October 27, 2008
Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 2
ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)
For additional information: https://www.karger.com/HRP
Abstract
Background/Aims: A 33-year-old man was referred for the first time to the Division of Neurology because of the presence and progression of neurological symptoms. Dysphagia, weakness, reduced tear production, and nasal speech were present. In order to point the attention of late-onset triple A syndrome we describe this case and review the literature. Methods: Hormonal and biochemical evaluation, Schirmer test, tilt test and genetic testing for AAAS gene mutations. Results: Late-onset triple A syndrome caused by a novel homozygous missense mutation in the AAAS gene (A167V in exon 6) was diagnosed at least 17 years after symptom onset. Conclusions: The association between typical signs and symptoms of triple A syndrome should suggest the diagnosis even if they manifest in adulthood. The diagnosis should be confirmed by Schirmer test, endocrine testing (both basal and dynamic), genetic analysis, and detailed gastroenterological and neurological evaluations. Awareness of the possible late onset of the disease and of diagnosis in adulthood is still poor among clinicians, the acquaintance with the disease is more common among pediatricians. The importance of an adequate multidisciplinary clinical approach, dynamic testing for early diagnosis of adrenal insufficiency and periodical reassessment of adrenal function are emphasized.
© 2008 S. Karger AG, Basel
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References
- Allgrove J, Clayden GS, Grant DB, Macaulay JC: Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet 1978;1:1284–1286.
-
Online Mendelian Inheritance in Man. OMIM (TM). Bethesda, Center for Medical Genetics, Johns Hopkins University, and National Center for Biotechnology Information, National Library of Medicine, 1999. URL: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=231550.
- Handschug K, Sperling S, Yoon SJ, Hennig S, Clark AJ, Huebner A: Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Hum Mol Genet 2001;10:283–290.
- Houlden H, Smith S, De Carvalho M, Blake J, Mathias C, Wood NW, Reilly MM: Clinical and genetic characterization of families with triple A (Allgrove) syndrome. Brain2002;125:2681–2690.
- Prpic I, Huebner A, Persic M, Handschug K, Pavletic M: Triple A syndrome: genotype-phenotype assessment. Clin Genet 2003;63:415–417.
- Clark AJ, Weber A: Adrenocorticotropin insensitivity syndromes. Endocr Rev 1998;19:828–843.
- Geffner ME, Lippe BM, Kaplan SA, Berquist WE, Bateman JB, Paterno VI, Seegan R: Selective ACTH insensitivity, achalasia, and alacrima: a multisystem disorder presenting in childhood. Pediatr Res 1983;17:532–536.
- Grant DB, Dunger DB, Smith I, Hyland K: Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia. Eur J Pediatr 1992;151:85–89.
- Moore PS, Couch RM, Perry YS, Shuckett EP, Winter JS: Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima. Clin Endocrinol 1991;34:107–114.
- Bentes C, Santos-Bento M, de Sá J, de Lurdes Sales Luís M, de Carvalho M: Allgrove syndrome in adulthood. Muscle Nerve 2001;24:292–296.
- Kimber J, McLean BN, Prevett M, Hammans SR: Allgrove or 4 ‘A’ syndrome: an autosomal recessive syndrome causing multisystem neurological disease. J Neurol Neurosurg Psychiatr 2003;74:654–657.
- Pedreira CC, Zacharin MR: Allgrove syndrome: when a recognizable paediatric disorder occurs in adulthood. Med J Aust 2004;180:74–75.
- Cronshaw JM, Matunis MJ: The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. Proc Natl Acad Sci USA 2003;100:5823–5827.
- Salehi M, Houlden H, Sheikh A, Poretsky L: The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene. Metabolism 2005;54:200–205.
- Nieman KL: Dynamic evaluation of adrenal hypofunction. J Endocrinol Invest 2003;26:74–82.
Article / Publication Details
Received: December 07, 2007
Accepted: February 28, 2008
Published online: October 27, 2008
Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 2
ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)
For additional information: https://www.karger.com/HRP