A Novel Variant of Adenosine Deaminase 2 Deficiency Presented With Chronic Thrombocytopenia, Anemia, and Early-Onset Stroke

Abdulqader Al-Hebshi,Naif Alshenaifi,Maryam Aloqbi,Waheed Turkistani,Maher Aljohani,Fahad Hakami

doi:10.7759/cureus.15288

Abstract

Deficiency of adenosine deaminase 2 (DADA2) is a rare recessive disorder caused by the bi-allelic loss-of-function pathogenic variants in the ADA2 gene (MIM: 607575, also known as CECR1, cat eye syndrome chromosome region, candidate 1). Based on the Human Gene Mutation Database (HGMD®), 53 different disease-causing variants have been identified in this gene to date. This case report aims to describe a new vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (VAIHS) case caused by a novel pathogenic variant. A four-year-old boy was referred to our hospital with anemia, thrombocytopenia, and stroke, but no skin manifestations. The patient had a significant phenotypic overlap with VAIHS. Molecular genetic analysis via whole exome sequencing identified a homozygous deleterious variant in ADA2. To our knowledge, the identified variant has never been described in the literature. Screening for ADA2 pathogenic variants should be considered in the differential diagnosis of pediatric patients manifesting with chronic thrombocytopenia or early-onset stroke for an accurate diagnosis and appropriate treatment choices.

Highlights

Deficiency of adenosine deaminase 2 (DADA2) is a rare recessive disorder caused by the bi-allelic loss-offunction pathogenic variants in the ADA2 gene (MIM: 607575, known as CECR1, cat eye syndrome chromosome region, candidate 1)
Screening for ADA2 pathogenic variants should be considered in the differential diagnosis of pediatric patients manifesting with chronic thrombocytopenia or early-onset stroke for an accurate diagnosis and appropriate treatment choices
Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal-recessive disorder caused by bi-allelic loss-of-function pathogenic variants in the ADA2 gene (MIM: 607575, known as CECR1, cat eye syndrome chromosome region, candidate 1)

Summary

Introduction

Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal-recessive disorder caused by bi-allelic loss-of-function pathogenic variants in the ADA2 gene (MIM: 607575, known as CECR1, cat eye syndrome chromosome region, candidate 1). A four-year-old boy was referred to our hospital with chronic immune thrombocytopenia, hemolytic anemia, and positive direct antiglobulin test (Table 1), and labeled as Evans syndrome His medical history indicated that the patient had an unremarkable history until the age of 18 months, when he presented with multiple skin bruises and spontaneous gum bleeding, along with pale appearance and fatigue. The WES confirmed the diagnosis and identified a novel homozygous 5 base pair deletion in ADA2 [NM_001282225.2: c.1447_1451del (p.Ser483fs)] It had no record in literature or any of the general population studies, including the Genome Aggregation Database (gnomAD) and the Exome Aggregation Consortium (ExAC). The patient received packed red blood cells and IVIG, 1 g/kg for two days He was prescribed oral eltrombopag (a thrombopoietin receptor agonist) 50 mg once daily and granulocyte colony-stimulating factor (G-CSF) at a dose of 50 mic/kg as a subcutaneous injection. The patient was transferred to a higher center to follow pediatric rheumatology and bone marrow transplant team for further evaluation and management

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Findings

Hershfield M