Myeloid dysplasia in familial 3-methylglutaconic aciduria

A kindred is reported with four members affected with neurodegenerative disorder and 3-methylglutaconic aciduria. Two siblings developed thrombocytopenia heralding a myelodysplastic syndrome; in one patient it evolved into acute myeloid leukemia with monosomy 7 in the marrow. The hematologic complications have hitherto not been previously reported in other cases of 3-methylglutaconic aciduria and are thus thought to represent a new disease entity. This family adds additional evidence to the genetic heterogeneity of Mendelian disorders in which the primary mutation may have a mutator effect that could give origin to myelodysplastic syndrome and acute myeloid leukemia through acquired chromosomal changes.