Case series of ADA-deficient patients characterised

Case series of ADA-deficient patients characterised

Published Date: 12/7/18

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medwireNews Researchers have characterised the clinical features and outcomes of 13 patients with adenosine deaminase (ADA) deficiency.

The patients were diagnosed between 2000 and 2017 at a Turkish institution, with the majority (n=10) receiving a diagnosis of severe combined immunodeficiency (SCID) at a median age of 4 months.

The remaining three were diagnosed at a median age of 22 months, and were thus considered to have delayed- or late-onset ADA deficiency. The researchers point out, however, that one of these three patients was identified at the age of 2 months, following the detection of ADA deficiency in his brother, but was still classed as having late-onset disease as his clinical features were less severe than those seen in SCID cases.

Another key difference between the groups was the level of ADA metabolites, which were significantly higher among the ADA-SCID patients than those with delayed- or late-onset disease, with erythrocyte deoxyadenosine nucleotide levels of 62.1% and 6.9%, respectively.

Of the 13 children, nine received enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEG)-ADA, while four did not – two because they were diagnosed before ERT became available in Turkey, one who was diagnosed post mortem, and one because they underwent early haematopoietic stem cell transplantation (HSCT).

Treatment with PEG-ADA only led to small increases in absolute lymphocyte counts and no significant improvements in the proportions of CD3+, CD19+ or CD16/56+ cells, but appeared to be sufficient to control symptoms in two patients with late-onset ADA deficiency, who continue to receive ERT, the researchers report in the Journal of Clinical Immunology.

For patients with ADA-SCID, however, the authors believe that the principle use of ERT is “to improve and stabilize clinical status”, thereby enabling the receipt of curative therapy.

In this case series, six children with ADA-SCID and one with late-onset ADA deficiency underwent allogeneic HSCT (four without pre-conditioning), while one ADA-SCID patient received gene therapy with a retroviral vector after reduced conditioning therapy.

Three of the seven HSCT-treated patients died approximately 1 month after treatment, but the rest remain alive at the time of analysis. One child – patient 6 – continued to require intravenous immunoglobulin (IVIG) therapy even after HSCT, despite having the less severe form of the condition, but the other three patients were able to stop.

The patient who underwent gene therapy was able to discontinue IVIG and receive vaccinations around 6 months post-treatment. Deniz Cagdas, from Hacettepe University Medical School in Ankara, Turkey, and co-authors report that although the child remains lymphopenic, on the whole he is well.

They also highlight that patient 6 was additionally diagnosed with juvenile polyposis, which led to serious complications, including recurrent hospitalisations, refractory hypoalbuminaemia and gastric outlet obstruction with duodenal intussusception requiring emergency surgery.

Noting that this appears to be the first case of polyposis in a patient with primary immune deficiency, the researchers stress the importance of endoscopic evaluation of polyposis in ADA-deficient patients who present with intractable diarrhoea and protein-losing enteropathy.

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