Florence Roucher-Boulez1,2,3, Aude Brac de la Perriere3,4, Aude Jacquez2, Delphine Chau2, Laurence Guignat5, Christophe Vial6, Yves Morel7,2,3, Marc Nicolino2,3,8, Gerald Raverot2,4, Michel Pugeat2,4. 1. Laboratoire de Biochimie et Biologie Moléculaire Grand EstUM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France florence.roucher@chu-lyon.fr. 2. Univ LyonUniversité Claude Bernard Lyon 1, Lyon, France. 3. Centre de Référence du Développement Génital: du Fœtus à l'AdulteFilière Maladies Rares Endocriniennes, Bron, France. 4. Fédération d'EndocrinologieGroupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 5. Service d'EndocrinologieCentre de Référence des Maladies Surrénaliennes Rares, Hôpital Cochin, Paris, France. 6. Service d'Electroneuromyographie et Pathologies NeuromusculairesGroupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 7. Laboratoire de Biochimie et Biologie Moléculaire Grand EstUM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 8. Service de Pédiatrie EndocrinologieGroupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.
Abstract
OBJECTIVE: Triple-A or Allgrove syndrome is an autosomal recessive disorder due to mutations in the AAAS gene, which encodes a nucleoporin named ALADIN. It is characterized by a classical clinical triad: alacrima, achalasia and adrenal insufficiency, the canonic symptoms that are associated with progressive peripheral neuropathy. Only a few cohorts have been reported. The objective of the present study was to characterize the various spectra of adrenal function in Triple-A patients. METHODS: A retrospective clinical and biological monitoring of 14 patients (10 families) was done in a single multidisciplinary French center. All had AAAS gene sequenced and adrenal function evaluation. RESULTS: Nine different AAAS mutations were found, including one new mutation: c.755G>C, p.(Trp252Ser). Regarding adrenal function, defects of the zona fasciculata and reticularis were demonstrated by increased basal ACTH levels and low DHEAS levels in all cases regardless of the degree of glucocorticoid deficiency. In contrast, mineralocorticoid function was always conserved: i.e., normal plasma renin level associated with normal aldosterone level. The main prognostic feature was exacerbation of neuropathy and cognitive disorders. CONCLUSIONS: These data suggest that, in Triple-A patients, adrenal function can be deficient, insufficient or compensated. In our cohort after the first decade of life, there does not appear to be any degradation of adrenal function over time. However, patients with compensated adrenal function should be informed and educated to manage a glucocorticoid replacement therapy in case of stressful conditions, with no need for systematic long-term treatment.
OBJECTIVE: Triple-A or Allgrove syndrome is an autosomal recessive disorder due to mutations in the AAAS gene, which encodes a nucleoporin named ALADIN. It is characterized by a classical clinical triad: alacrima, achalasia and adrenal insufficiency, the canonic symptoms that are associated with progressive peripheral neuropathy. Only a few cohorts have been reported. The objective of the present study was to characterize the various spectra of adrenal function in Triple-A patients. METHODS: A retrospective clinical and biological monitoring of 14 patients (10 families) was done in a single multidisciplinary French center. All had AAAS gene sequenced and adrenal function evaluation. RESULTS: Nine different AAAS mutations were found, including one new mutation: c.755G>C, p.(Trp252Ser). Regarding adrenal function, defects of the zona fasciculata and reticularis were demonstrated by increased basal ACTH levels and low DHEAS levels in all cases regardless of the degree of glucocorticoid deficiency. In contrast, mineralocorticoid function was always conserved: i.e., normal plasma renin level associated with normal aldosterone level. The main prognostic feature was exacerbation of neuropathy and cognitive disorders. CONCLUSIONS: These data suggest that, in Triple-A patients, adrenal function can be deficient, insufficient or compensated. In our cohort after the first decade of life, there does not appear to be any degradation of adrenal function over time. However, patients with compensated adrenal function should be informed and educated to manage a glucocorticoid replacement therapy in case of stressful conditions, with no need for systematic long-term treatment.
Authors: Erica L Macke; Joel A Morales-Rosado; Sarah K Macklin-Mantia; Christopher T Schmitz; Björn Oskarsson; Eric W Klee; Klaas J Wierenga Journal: Mol Genet Genomic Med Date: 2022-05-15 Impact factor: 2.473