Adenosine Deaminase Deficiency in Adults

Author:

Ozsahin Hulya1,Arredondo-Vega Francisco X.1,Santisteban Ines1,Fuhrer Hanspeter1,Tuchschmid Peter1,Jochum Wolfram1,Aguzzi Adriano1,Lederman Howard M.1,Fleischman Amy1,Winkelstein Jerry A.1,Seger Reinhard A.1,Hershfield Michael S.1

Affiliation:

1. From the Division of Immunology/Hematology, University Children's Hospital, Zurich, Switzerland; the Departments of Medicine and Biochemistry, Duke University School of Medicine, Durham, NC; the Department of Medicine. Triemli Hospital, Zurich Switzerland; the Neuropathology Institute of the University of Zurich, Switzerland; and the Eudowood Division of Pediatric Immunology, The Johns Hopkins University School of Medicine, Baltimore, MD.

Abstract

AbstractAdenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenotypes. Patient no. 1 (39 years of age) had combined immunodeficiency. She had frequent infections, lymphopenia, and recurrent hepatitis as a child but did relatively well in her second and third decades. Then she developed chronic sinopulmonary infections, including tuberculosis, and hepatobiliary disease; she died of viral leukoencephalopathy at 40 years of age. Patient no. 2, a healthy 28-year-old man with normal immune function, was identified after his niece died of SCID. Both patients lacked erythrocyte ADA activity but had only modestly elevated deoxyadenosine nucleotides. Both were heteroallelic for missense mutations: patient no. 1, G216R and P126Q (novel); patient no. 2, R101Q and A215T. Three of these mutations eliminated ADA activity, but A215T reduced activity by only 85%. Owing to a single nucleotide change in the middle of exon 7, A215T also appeared to induce exon 7 skipping. ADA deficiency is treatable and should be considered in older patients with unexplained lymphopenia and immune deficiency, who may also manifest autoimmunity or unexplained hepatobiliary disease. Metabolic status and genotype may help in assessing prognosis of more mildly affected patients.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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