Search for a rare disease
Other search option(s)
RAS-associated autoimmune leukoproliferative disease
RAS-associated autoimmune leukoproliferative disease (RALD) is a rare genetic disorder characterized by monocytosis, autoimmune cytopenias, lymphoproliferation, hepatosplenomegaly, and hypergammaglobulinemia.
- Prevalence: <1 / 1 000 000
- Inheritance: Unknown
- Age of onset: Childhood, Infancy
- ICD-10: D72.8
- OMIM: 614470
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Prevalence of this disorder is not known. It is extremely rare with fewer than 20 patients reported to date.
Age of onset of the clinical signs is invariably in infancy or early childhood. Most patients have atypical features such as elevated counts for cells of myeloid origin (monocytosis and granulocytosis) making their clinical presentation indistinguishable from juvenile myelomonocytic leukemia (JMML; see this term). Many patients undergo repeated bone marrow assessments showing normal cytogenetics despite dysplastic marrow morphology. Lymphoma in adulthood in one patient and only one case of unexplained sudden death in adolescence have been reported. Hypergammaglobulinemia, autoantibodies and expansion of B lymphocytes in peripheral blood have also been noted.
RALD is caused by somatic mutations in the NRAS (1p13.2) and KRAS (12p12.1) genes encoding RAS proteins involved in regulating cell proliferation causing impairment of the intrinsic apoptosis pathway.
Double-negative T-cells (DNTs) may be mildly elevated in patients with RALD but are usually normal. Apoptosis assay can identify these patients due to their distinct cellular phenotype showing impaired cell death following serum or IL2 withdrawal.
The pattern of inheritance for RALD is not known. RAS mutations are considered somatic and limited to the circulating peripheral blood mononuclear cells.