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Sicilian family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and lethal lung disease in one of the affected brothers

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Abstract

Introduction

We report the clinical and immunological features of the autoimmune regulator gene (AIRE) in two Sicilian brothers with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). They were compound heterozygotes with R203X/R257X. Both had oral candidiasis since the first year of life and later developed hypoparathyroidism and Addison disease. The elder brother had experienced recurrent lower respiratory infections since 5 years of age and over the years developed severe obstructive lung disease with bronchiectasis, which led to death at 18 years of age. Both brothers had circulating autoantibodies against tryptophan hydroxylase and serotonin-producing cells were absent in the duodenal mucosa. This was associated with intestinal dysfunction in only the elder brother.

Conclusion

(1) In the first Sicilian family with APECED reported up to now we found a heterozygous mutation that had been previously reported only once. (2) In the older brother of this family we observed a severe and lethal lung disease; this case adds to a growing literature describing this association between APECED and respiratory illnesses. (3) Tryptophan hydroxylase antibodies might be hypothesized to be the marker of an autoimmune gastrointestinal illness possibly associated with APECED.

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Abbreviations

AADC:

L-amino acid decarboxylase autoantibodies

AIRE:

autoimmune regulator gene

APECED:

autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

CT:

computed tomography

EMA:

endomysium autoantibodies

FEV1 :

forced expiratory volume in 1 s

FoxP3:

forkhead box protein P3

FVC:

forced vital capacity

GADA:

glutamic acid decarboxylase autoantibodies

HLA:

human leukocyte antigen

IA2A:

islet second autoantigen autoantibodies

ICA:

islet cell autoantibodies

IFA:

intrinsic factor autoantibodies

LKMA:

liver-kidney microsomal autoantibodies

MPCA:

melanin-producing cells autoantibodies

NOD:

nonobese diabetic

PCA:

parietal cell autoantibodies

sccA:

side chain cleavage autoantibodies

SDS:

standard deviation score

StCA:

steroid-producing cells autoantibodies

TGHA:

thyroglobulin autoantibodies

TMHA:

thyroid microsomal autoantibodies

TPHA:

tryptophan hydroxylase antibodies

17αOHA:

17 alpha-hydroxylase autoantibodies

21OHA:

21-hydroxylase autoantibodies TCR (T-cell receptor)

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Acknowledgements

This study was supported by the EU Research Project FP-6 entitled: EurAPS: Autoimmune polyendocrine syndrome type I–a rare disorder of childhood as a model for autoimmunity, contract number LSHM-CT 2005–005223.

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Authors and Affiliations

  1. Department of Pediatrics, University of Messina, Via Consolare Valeria, 98125, Messina, Italy

    Filippo De Luca, Mariella Valenzise, Teresa Arrigo, Giuseppe Crisafulli & Giuseppina Salzano

  2. Department of Pathology Azienda Ospedaliera-Università Padova, Padova, Italy

    Rita Alaggio

  3. Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy

    Sara Cervato, Barbara Mariniello, Francesca Lazzarotto & Corrado Betterle

Authors
  1. Filippo De Luca
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  2. Mariella Valenzise
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  3. Rita Alaggio
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  4. Teresa Arrigo
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  5. Giuseppe Crisafulli
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  7. Sara Cervato
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  10. Corrado Betterle
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Correspondence to Filippo De Luca.

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De Luca, F., Valenzise, M., Alaggio, R. et al. Sicilian family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and lethal lung disease in one of the affected brothers. Eur J Pediatr 167, 1283–1288 (2008). https://doi.org/10.1007/s00431-008-0668-3

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  • DOI: https://doi.org/10.1007/s00431-008-0668-3

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