Original articles
Cognitive and behavioral abnormalities in adenosine deaminase deficient severe combined immunodeficiency☆,☆☆,★

https://doi.org/10.1067/mpd.2001.115023Get rights and content

Abstract

Objective: The objective was to evaluate the cognitive, behavioral, and neurodevelopmental function in patients with adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID) and to compare the findings with those of a case control group of patients without ADA-SCID. Study design: Case-matched pairs of patients with ADA-SCID (n = 11) and patients without ADA-SCID who had undergone bone marrow transplantation were recruited. Subjects were assessed by age-appropriate standard tests of intelligence, behavior, and neurodevelopment. Results: Cognitive ability was not significantly different between the 2 groups, but patients with ADA-SCID showed a significant inverse correlation between deoxyadenosinetrisphosphate levels at diagnosis and IQ (P =.048). Behavioral assessment showed that patients with ADA-SCID functioned in the pathologic range on all domains, whereas mean scores for the control group were within normal limits. Behavioral impairment in patients with ADA-SCID also showed a significant positive correlation with age (P =.026). Conclusions: Cognitive function in ADA deficiency is adversely affected by the severity of metabolic derangement at the time of diagnosis. In addition, patients with ADA-SCID have significant behavioral abnormalities after transplantation. These defects are not due to the transplant procedure but reflect the systemic nature of ADA deficiency. These findings have important implications for future medical and nonmedical management strategies. (J Pediatr 2001;139:44-50)

Section snippets

Patients and Control Group

All patients with ADA-SCID who had undergone BMT (n = 13) and were under follow-up at the Great Ormond Street Hospital for Children were eligible for inclusion in the study; 11 patients with ADA-SCID were recruited along with 11 patients who underwent BMT for other forms of SCID (4 recombinase activating gene defects, C2, C6, C9, C10; 3 X-linked SCID, C7, C8, C11; and 4 undefined SCID forms). Two patients with ADA-SCID did not respond to requests for inclusion in the study. The patients in the

Patient Characteristics

All patients with ADA-SCID were matched for sex with the members of the control group (Table).

Table. ADA-SCID and control patient characteristics

ADA-SCIDSexAge (y)Age at BMT (mo)Type of BMTControl groupSexAge (y)Age at BMT (mo)Type of BMT
Patient 1F186Haplo/No condC1F1960Haplo/cond
Patient 2F61MSD/No condC2F71Haplo/cond
Patient 3F25MSD/No condC3F37Haplo/cond
Patient 4F131Haplo/condC4F125Haplo/cond
Patient 5F1416MSD/No condC5F106MSD/No cond
Patient 6F46MFD/No condC6F54MUD/cond
Patient 7M23MFD/No condC7M

DISCUSSION

Since ADA deficiency was identified as a cause of severe immunologic abnormalities, many nonimmunologic consequences have been identified. Hirschhorn et al10 described a child with severe motor and pyramidal defects, nystagmus, and global developmental delay whose abnormalities ameliorated with enzyme replacement therapy, suggesting a metabolically induced neurologic defect. Large studies of recipients of BMT for hematologic malignancy have shown that transplantation in patients <3 years of age

Acknowledgements

We thank all of the participants in the study and their parents. Part of this study was submitted for an MSc dissertation at the City University, London, during which time Mary Rogers was supervised by Frances Stanton. We also thank Prof J. Stevenson and Dr Anne Simmonds for critical reading of the manuscript and Dr Angie Wade for statistical advice.

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    ☆

    Mary Haslinger Rogers was supported by a grant from the Children’s Research Fund.

    ☆☆

    This work was undertaken (in part) by Great Ormond Street Hospital for Children NHS Trust, which received a proportion of its funding from the NHS Executive; the views expressed in this publication are those of the authors and not necessarily those of the NHS Executive.

    ★

    Reprint requests: Hubert B. Gaspar, MBBS, MRCP, PhD, Molecular Immunology Unit, Institute of Child Health, 30 Guilford St, London WC1N 1E, United Kingdom.

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