Top

Published in:

Open Access 01-12-2017 | Case Report

Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report

Authors: Magdalena Dziedzic, Agata Marjańska, Katarzyna Bąbol-Pokora, Anna Urbańczyk, Elżbieta Grześk, Wojciech Młynarski, Sylwia Kołtan

Published in: Pediatric Rheumatology | Issue 1/2017

Abstract

Background

Pediatric autoinflammatory diseases are rare and still poorly understood conditions resulting from defective genetic control of innate immune system, inter alia from anomalies of NOD2 gene. The product of this gene is Nod2 protein, taking part in maintenance of immune homeostasis. Clinical form of resultant autoinflammatory condition depends on NOD2 genotype; usually patients with NOD2 defects present with Blau syndrome, NOD2-associated autoinflammatory disease (NAID) or Crohn’s disease.

Case presentation

We present the case of a 7-year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and NAID. Overlapping manifestations of two syndromes raised a significant diagnostic challenge, until next-generation molecular test (NGS) identified presence of three pathogenic variants of NOD2 gene: P268S, IVS8₊₁₅₈, 1007 fs, and established the ultimate diagnosis.

Conclusion

Presence of multiple genetical abnormalities resulted in an ambiguous clinical presentation with overlapping symptoms of Blau syndrome and NAID. Final diagnosis of autoinflammatory disease opened new therapeutic possibilities, including the use of biological treatments.

Yao Q, Zhou L, Cusumano P, Bose N, Piliang M, Jayakar B, et al. A new category of autoinflammdisease associated with NOD2 gene mutations. Arthritis Res Ther. 2011;13:R148.CrossRefPubMedPubMedCentral

Philpott DJ, Sorbara MT, Robertson SJ, Croitoru K, Girardin SE. NOD proteins: regulators of inflammation in health and disease. Nat Rev Immunol. 2014;14:9–23.CrossRefPubMed

Aróstegui JI, Arnal C, Merino R, Modesto C, Antonia Carballo M, Moreno P, et al. NOD2 gene-associated pediatric granulomatous arthritis. Arthritis Rheum. 2007;56:3805–13.CrossRefPubMed

Borzutzky A, Fried A, Chou J, Bonilla FA, Kim S, Dedeoglu F. NOD2-associated diseases: bridging innate immunity and autoinflammation. Clin Immunol. 2010;134:251–61.CrossRefPubMed

Caso F, Galozzi P, Costa L, Sfriso P, Cantarini L, Punzi L. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn’s disease. RMD Open. 2015;20:1.

The registry of Hereditary Auto-inflammatory Disorders Mutations. A HGVS affiliated database. http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=6. Accessed 7 Jan 2017.

Yao Q, Shen M, McDonald C, Lacbawan F, Moran R, Shen B. NOD2-associated autoinflammatory disease: a large cohort study. Rheumatology. 2015;54:1904–12.CrossRefPubMed

Yao Q, Shen M, Fernandez J. NOD2-associated autoinflammatory disease and immune deficiency. J Allergy Clin Immunol Pract. 2016;4:780–2.CrossRefPubMed

Yao Q, Su LC, Tomecki KJ, Zhou L, Jayakar B, Shen B. Dermatitis as a characteristic phenotype of a new autoinflammatory disease associated with NOD2 mutations. J Am Acad Dermatol. 2013;68:624–31.CrossRefPubMed

10.

Pardeo M, Cortis E, Bracaglia C, Nicolai R, De Benedetti F, Insalaco A. P03-012 - A P268S NOD2 mutation in one Blau patient. Pediatr Rheumatol Online J. 2013;11:A208.CrossRefPubMedCentral

11.

Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S, et al. Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-B activation: common genetic etiology with Blau syndrome. Blood. 2005;105:3.CrossRef

12.

Iwasaki T, Kaneko N, Ito Y, Takeda H, Sawasaki T, Heike T, et al. Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis. Sci World J. 2016; doi:10.1155/2016/2597376.

13.

Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol. 2013;174:203–11.PubMedPubMedCentral

14.

Caso F, Costa L, Rigante D, Vitale A, Cimaz R, Lucherini OM, et al. Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis. Autoimmun Rev. 2014;13:1220–9.CrossRefPubMed

Title: Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report
Authors: Magdalena Dziedzic
Agata Marjańska
Katarzyna Bąbol-Pokora
Anna Urbańczyk
Elżbieta Grześk
Wojciech Młynarski
Sylwia Kołtan
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Pediatric Rheumatology / Issue 1/2017
Electronic ISSN: 1546-0096
DOI: https://doi.org/10.1186/s12969-017-0188-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report

Abstract

Background

Case presentation

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Case presentation

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2017

Observational study of Interleukin-21 (IL-21) does not distinguish Kawasaki disease from other causes of fever in children

“HLA-G 3′UTR gene polymorphisms and rheumatic heart disease: a familial study among South Indian population”

Harnessing interactive technologies to improve health outcomes in juvenile idiopathic arthritis

TLR4 rs41426344 increases susceptibility of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population

Risk of tuberculosis among Alabama children and adolescents treated with tumor necrosis factor inhibitors: a retrospective study

Comics as an educational tool for children with juvenile idiopathic arthritis