The Journal of clinical endocrinology and metabolism · 2016
A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Bruserud Øyvind, Oftedal Bergithe E, Landegren Nils, Erichsen Martina M, Bratland Eirik, Lima Kari, Jørgensen Anders P, Myhre Anne G, Svartberg Johan, Fougner Kristian J, Bakke Åsne, Nedrebø Bjørn G, Mella Bjarne, Breivik Lars, Viken Marte K, Knappskog Per M, Marthinussen Mihaela C, Løvås Kristian, Kämpe Olle, Wolff Anette B, Husebye Eystein S
Аннотация
CONTEXT: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse.
OBJECTIVE: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996-2016).
PATIENTS: All known Norwegian patients with APS1.
RESULTS: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes.
CONCLUSIONS: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center.
OBJECTIVE: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996-2016).
PATIENTS: All known Norwegian patients with APS1.
RESULTS: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes.
CONCLUSIONS: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center.
Предметные рубрики MeSH
AdolescentAdultAutoantibodiesChildChild, PreschoolDNA Mutational AnalysisDisease ProgressionFemaleFollow-Up StudiesGenetic Association StudiesHumansInfantLongitudinal StudiesMaleMiddle AgedNorwayPhenotypePolyendocrinopathies, AutoimmunePrognosisRegistriesSurvival AnalysisTranscription FactorsYoung AdultAIRE Protein