Maternal T-cell engraftment may delay ADA-SCID diagnosis

Maternal T-cell engraftment may delay ADA-SCID diagnosis

Published Date: 13/6/19

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medwireNews: Engraftment of maternally derived T cells could complicate the diagnosis of adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) in the child, say the authors of a case report.

The team from ASST Spedali Civili of Brescia in Italy describes a child who presented at the age of 3.2 months with “a history of frequent bronchiolitis associated with dermatitis and mycosis.” She had severe lymphopenia, with, for instance, a CD3+ cell count of 189 cells/μL compared with levels of 3180–5401 cells/μL observed in a healthy paediatric population, and CD19+ levels of 2 versus a healthy level of 315–1383 cells/μL.

The child also had low levels of immunoglobulin gamma, at 207 mg/dL versus 270–1100 mg/dL in healthy children.

The authors point out that although the patient exhibited various clinical and laboratory features characteristic of ADA-SCID, “she lacked the typical physical and radiological features of ADA-SCID”, such as growth failure, rib abnormalities, pelvic dysplasia and platyspondylia.

Moreover, the patient’s ADA enzyme activity was 0.54 U per gram of haemoglobin, which although lower than the healthy control range of 0.80–2.50 U per gram of haemoglobin indicated the presence of residual enzymatic activity.

Further investigation showed total deoxyadenosine nucleotide levels of 0.629 μmol/mL of red blood cells, which was considerably higher than healthy control levels of less than 0.005 μmol/mL of red blood cells.

And sequencing of the ADA coding exons as well as introns seven and eight revealed two mutations, namely, p.Ser291Leu and p.Leu298Pro.

As a result of these findings, the child was diagnosed with ADA-SCID at the age of 3.4 months and was given enzyme replacement therapy alongside intravenous administration of immunoglobulins. At 11 months, she underwent haematopoietic stem cell transplantation with bone marrow from a matched unrelated donor, which led to full immune reconstitution.

The child was 26 months old at the time of reporting and in good health, without any signs of graft-versus-host disease, say Arnalda Lanfranchi and colleagues in Clinical Immunology.

Investigating the reasons for the lack of typical ADA-SCID features and residual ADA activity, they discovered engraftment of maternal T cells, such that 79.3% of the child’s T lymphocytes were of maternal origin according to variable number of tandem repeat analysis.

This is the first reported instance of maternal T-cell engraftment in the ADA-SCID setting, note the authors, highlighting that the presence of maternal T cells was “misleading” and “could have delayed the identification of ADA-SCID.”

© 2019 Springer Healthcare Ltd

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