Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene

•This pediatric case has unusually mild form of fumaric aciduria.•He has a known (c.1431_1433dupAAA) and a novel (c.782G>T) mutation in FH gene.•Heterozygous mutations in FH gene also cause tumors.•The father who was carrier of c.1431_1433dupAAA mutation had cutaneous leiomyoma.

Mutations in the FH gene cause the deficiency of the enzyme fumarase (fumarate hydratase, EC 4.2.1.2) which result in autosomal recessive fumaric aciduria in early childhood with failure to thrive, seizures, developmental delay, mental retardation, hypotonia and sometimes with polycythemia, leukopenia, and neutropenia. Many children with fumarate hydratase deficiency do not survive infancy or childhood; those surviving beyond childhood have severe psychomotor retardation. Recently, FH gene was also identified as a “non-classical” tumor suppressor gene and heterozygous mutations were shown to cause multiple cutaneous and uterine leiomyomas as well as hereditary leiomyomatosis and renal cell cancer. A male patient who was referred to investigate the etiology of psychomotor retardation was later diagnosed to have fumaric aciduria due to the combination of a previously known (c.1431_1433dupAAA) and a novel (c.782G>T) mutation. The patient had an unusually mild clinical course without acidotic attacks. Interestingly his father who was heterozygous for the c.1431_1433dupAAA mutation in the FH gene had cutaneous leiomyoma.