title: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome: time to review diagnostic criteria?
abstract: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive syndrome defined by two of the following conditions: chronic mucocutaneous candidiasis, hypoparathyroidism, or Addison's disease. Other autoimmune conditions may be associated, such as hypothyroidism, hypogonadism, insulin-dependent diabetes mellitus, chronic active hepatitis, pernicious anemia, vitiligo, alopecia, biliary cirrhosis, and ectodermal dysplasia. APECED is caused by mutations in the autoimmune regulator gene, mapping to 21q22.3. We report on three patients whose clinical and molecular features challenge the currently used diagnostic criteria for APECED. AR presented at 15 yr of age with a history of recurrent infections and mucocutaneous candidiasis. He is now 21 yr old, and no other signs or symptoms of APECED have appeared to date. DR presented at 7 yr of age with hypocalcemia and a prolonged Q-T interval on the electrocardiogram. He also had minor facial dysmorphisms and mild mental retardation. Serum calcium levels were low, PTH levels were undetectable, and hypoparathyroidism was therefore diagnosed. All other biochemical, immunological, and endocrinological tests were normal. DR is now 8 yr old with no other signs or symptoms of APECED. ST presented at 14 yr of age for alopecia aerata and pitted nail dystrophy and goiter. Thyroid function was normal in the presence of thyroid-specific antibodies. No other signs or symptoms of APECED have appeared to date. Genetic analysis revealed a typical mutation (R257X) on a single allele in both AP and DR; in ST, heterozygosity for a novel mutation (V484M) involving one of the zinc fingers of the plant homeodomain of the protein was found. The finding of a typical APECED mutation in two patients presenting with one isolated major clinical APECED feature and of a novel mutation in a patient presenting with atypical features of APECED onset suggests that the time might have come for updating the diagnostic criteria of this syndrome.
authors.affiliation: Pediatric Department and Institute of Molecular Medicine A. Nocivelli, University of Brescia, 25123 Brescia, Italy. mazzolar@master.cci.unibs.it
authors.forename: F
authors.initials: F
authors.lastname: Buzi
authors.forename: R
authors.initials: R
authors.lastname: Badolato
authors.forename: C
authors.initials: C
authors.lastname: Mazza
authors.forename: S
authors.initials: S
authors.lastname: Giliani
authors.forename: Lucia D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: G
authors.initials: G
authors.lastname: Radetti
authors.forename: A
authors.initials: A
authors.lastname: Plebani
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
mesh_terms: D000293:Adolescent; D000506:Alopecia Areata / Q000175:diagnosis / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D006996:Hypocalcemia / Q000175:diagnosis / Q000235:genetics; D007011:Hypoparathyroidism / Q000175:diagnosis / Q000235:genetics; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics; D008297:Male; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis* / Q000235:genetics*