title: Cavitating leukoencephalopathy with multiple mitochondrial dysfunction syndrome and NFU1 mutations.
abstract: Multiple Mitochondrial Dysfunction Syndrome (MMDS) comprises a group of severe autosomal recessive diseases with onset in early infancy and characterized by a systemic disorder of energy metabolism, resulting in weakness, respiratory failure, lack of neurological development, lactic acidosis, and early death. Biochemical findings include defects of complexes I, II, and III of the mitochondrial respiratory chain and severe deficiency of Pyruvate dehydrogenase complex (PDHc). Three genes have been associated with MMDS since now: NFU1, BOLA3, and IBA57. We describe an Italian male patient presenting with severe psychomotor regression after an infectious episode, lactic acidosis, hyperglycinemia, reduction of respiratory chain complex II associated with a marked deficiency of PDHc activity. He carried two heterozygous mutations in NFU1, one novel (p.Cys210Phe) and one previously reported (p.Gly189Arg) missense change affecting highly conserved residues. A severe leukoencephalopathy with cavitations in deep white matter was disclosed at brain MRI, suggesting a peculiar neuroradiological phenotype associated with defect in this gene.
authors.affiliation: Unit of Molecular Neurogenetics, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.affiliation: Unit of Child Neurology, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ardissone
authors.affiliation: Unit of Molecular Neurogenetics, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.affiliation: Unit of Molecular Neurogenetics, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.affiliation: Unit of Molecular Neurogenetics, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.affiliation: Unit of Neuroradiology, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Farina
authors.affiliation: Unit of Molecular Neurogenetics, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Ghezzi
authors.affiliation: Unit of Child Neurology, Istituto Neurologico "Carlo Besta," Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Moroni
keywords: MMDS1; NFU1; brain MRI; leukoencephalopathy; mitochondrial disorders; multiple mitochondrial dysfunction syndrome