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RMD Open. 2016 May 16;2(1):e000236. doi: 10.1136/rmdopen-2015-000236. eCollection 2016.

ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters.

Author information

1
Pediatric Immunology-Hematology and Rheumatology Unit, Institut Imagine, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France; Transversal Unit of Allergology and Rheumatology, CHRU Tours, Tours, France.
2
Laboratory of Rare and Autoinflammatory Genetic Diseases , CHRU , Montpellier , France.
3
INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Hôpital Necker, Paris Descartes-Sorbonne Paris Cité University , Paris , France.
4
Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester , Manchester , UK.
5
Inserm U930, CNRS 2448, Tours, France; Service Neuropédiatrie et Handicaps, CHRU de Tours, Tours, France.
6
Pediatric Emergency Unit , CHRU Tours , Tours , France.
7
Pediatric Neurology Department , National Referral Center for Neuro-Inflammatory Diseases in Children, Hôpitaux Universitaires Paris Sud, Assistance Publique-Hôpitaux de Paris and UMR 1184, Center for Immunology of viral infections and autoimmune diseases, University Paris Sud , Le Kremlin-Bicêtre , France.
8
INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Hôpital Necker, Paris Descartes-Sorbonne Paris Cité University, Paris, France; Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
9
Pediatric Immunology-Hematology and Rheumatology Unit , Institut Imagine, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris , Paris , France.

Abstract

The objective of this paper is to: describe the phenotype compound heterozygote for mutations in CECR1 in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa. Subsequently, two cerebral lacunar lesions were identified following a brain stroke. Clinical features improved on anti-tumour necrosis factor therapy. The first patient's sister demonstrated early-onset, long-lasting anaemia with mild biological inflammation; at the ages of 3 and 5 years, she had presented 2 acute, transient neurological events with lacunar lesions on MRI. CECR1 sequencing identified both sisters to be compound heterozygous for a p.Tyr453Cys mutation and a previously undescribed deletion of exon 7. ADA2 activity was reduced by 50%. Neutrophil-stimulated genes were not overexpressed, but interferon-stimulated genes were. The expression of a panel of other cytokine transcripts was not significantly altered. In conclusion, searching for CECR1 mutation or assessing ADA2 activity should be considered in patients with an atypical presentation of inflammatory disease.

KEYWORDS:

Fever Syndromes; Inflammation; Systemic vasculitis

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