Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes.
A 7-month-old boy died in a demented state after a clinical history characterized by generalized seizures, psychomotor deterioration, and fumaric aciduria. We found a marked deficiency of both mitochondrial and cytosolic fumarases in skeletal muscle, brain, cerebellum, heart, kidney, liver, and cultured fibroblasts. Fumarase activities were 30 to 50% compared with controls in both mitochondria and cytosol from cultured fibroblasts of the parents. Antifumarase cross-reacting material was present in negligible amounts in the patient's tissues. Our data indicate that this disease is an autosomal recessive encephalopathy, due to a single mutation affecting the gene encoding both forms of the enzyme.
Gellera
C
C
Division of Biochemistry and Genetics, Istituto Neurologico C. Besta, Milano, Italy.
Uziel
G
G
Rimoldi
M
M
Zeviani
M
M
Laverda
A
A
Carrara
F
F
DiDonato
S
S
D000143:Acids / Q000097:blood / Q000652:urine; D015153:Blotting, Western; D001928:Brain Diseases, Metabolic / Q000201:enzymology / Q000235:genetics*; D002331:Carnitine / Q000097:blood / Q000652:urine; D002849:Chromatography, Gas; D002869:Chromosome Aberrations / Q000378:metabolism; D025063:Chromosome Disorders; D003600:Cytosol / Q000201:enzymology* / Q000378:metabolism; D005649:Fumarate Hydratase / Q000172:deficiency*; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism
D000143:Acids; D007527:Isoenzymes; D005649:Fumarate Hydratase; D002331:Carnitine