Variable phenotype of severe immunodeficiencies associated with RMRP gene mutations.

Purpose: Mutations in RMRP primarily give rise to Cartilage Hair Hypoplasia (CHH), a highly diverse skeletal disorder which can be associated with severe immunodeficiency. Increased availability of RMRP mutation screening has uncovered a number of infants with significant immunodeficiency but only mild or absent skeletal features. We surveyed the clinical and immunological phenotype of children who have undergone allogeneic haematopoietic stem cell transplantation for this condition in the UK.

Methods: Thirteen patients with confirmed RMRP mutations underwent allogeneic stem cell transplantation (SCT) at two nationally commissioned centres using a variety of donors and conditioning regimens. Records were retrospectively reviewed.

Results: Median time from clinical presentation to diagnosis was 12 months (range 1 to 276 months), with three infants diagnosed with severe combined immunodeficiency (SCID) without radiographical manifestations of CHH. A total of 17 allogeneic procedures were performed on 13 patients including two stem-cell top-ups. The median age at transplant was 32.4 months (range 1.5 to 125 months). Of the eleven surviving patients, median follow-up was 50 months (range 21.6 to 168 months).

Conclusions: RMRP mutations can cause short stature and significant immunodeficiency which can be corrected by allogeneic SCT and the diagnosis should be considered even in the absence of skeletal manifestations.