HEMATOLOGICAL ABNORMALITIES AND CHOLESTATIC LIVER-DISEASE IN 2 PATIENTS WITH MEVALONATE KINASE-DEFICIENCY

We describe two patients with mevalonate kinase deficiency and promine nt hematologic abnormalities and cholestatic liver disease. Patient R. B. was not anemic at birth, but developed petechiae and cutaneous extr amedullary hematopoiesis, hepatosplenomegaly, leukocytosis, and recurr ent febrile events without positive bacterial or viral cultures. Patie nt N.M. manifested minor anomalies, hepatosplenomegaly, anemia, thromb ocytopenia, recurrent febrile crises, and facial rashes. Mevalonic aci duria was found by urinary organic acid analysis, and mevalonate kinas e deficiency was documented in both. The clinical spectrum of normocyt ic hypoplastic anemia, leukocytosis, thrombocytopenia, and abnormal bl ood cell forms led to diagnoses of congenital infection, myelodysplast ic syndromes, or chronic leukemia in these patients before recognition of mevalonate kinase deficiency. Mevalonate kinase deficiency represe nts a single-gene abnormality that may be associated with significant hematologic findings. Recognition of the variability of this disorder with some patients manifesting only mild neurologic findings, yet sign ificant hepatosplenomegaly, normocytic anemia, thrombocytopenia, and l eukocytosis is important for all specialists who need to be aware of t his organic aciduria, (C) 1998 Wiley-Liss, Inc.