Background:
High consanguinity rate among certain populations in the Middle East accounts for a high incidence of severe combined immunodeficiency (SCID) resulting from autosomal recessive (AR) mutations. We present a large and unique cohort of patients diagnosed with SCID due to recombination-activating genes 1 or 2 (RAG1 or RAG2) mutations.
Methods:
26 RAG1/RAG2 deficient SCID patients were retrospectively analyzed by clinical presentation, immunologic phenotype, genetic analysis, treatment, including hematopoietic stem cell transplantation (HSCT), and outcome.
Results:
Most patients were males, and of Muslim Arab descent. Majority of patients were born to consanguineous parents, and 65% had family history of immunodeficiency. Most patients suffered of various infections by the time they turned two months old, eight patients presented with Omenn Syndrome, three patients had maternal engraftment and seven patients suffered from vaccine derived infections, including a rare case of vaccine strain Measles encephalitis. TREC was found to be the single most sensitive screening test. 19 patients underwent HSCT at a median age of six months, with a successful outcome for most of them.
Genetic analysis revealed 11 different mutations, two of those novel mutations, with a phenotypic variability.
Conclusion:
AR SCID is more prevalent in communities with high rate of consanguine marriages, where a genetic founder effect is detected. Clinical phenotype is variable, and outcome relies upon early diagnosis, avoidance of harmful administration of live vaccines, and an early curative HSCT.
We call for implementation of newborn SCID screening in the Palestinian population, which will surely improve diagnosis and save lives.
