Cavitating leukoencephalopathy with multiple mitochondrial dysfunction syndrome and NFU1 mutations

Federica Invernizzi, Anna Ardissone, Eleonora Lamantea, Barbara Garavaglia, Massimo Zeviani, Laura Farina, Daniele Ghezzi, Isabella Moroni

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Article number412
JournalFrontiers in Genetics
Volume5
Issue numberNOV
DOIs
Publication statusPublished - 2014

Fingerprint

Leukoencephalopathies
Lactic Acidosis
Pyruvate Dehydrogenase Complex Deficiency Disease
Pyruvate Dehydrogenase Complex
Mitochondrial Diseases
Mutation
Electron Transport
Respiratory Insufficiency
Energy Metabolism
Genes
Phenotype
Brain
Multiple Mitochondrial Dysfunctions Syndrome
White Matter
respiratory complex II

Keywords

  • Brain MRI
  • Leukoencephalopathy
  • Mitochondrial disorders
  • MMDS1
  • Multiple mitochondrial dysfunction syndrome
  • NFU

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Cavitating leukoencephalopathy with multiple mitochondrial dysfunction syndrome and NFU1 mutations. / Invernizzi, Federica; Ardissone, Anna; Lamantea, Eleonora; Garavaglia, Barbara; Zeviani, Massimo; Farina, Laura; Ghezzi, Daniele; Moroni, Isabella.

In: Frontiers in Genetics, Vol. 5, No. NOV, 412, 2014.

Research output: Contribution to journalArticle

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AU - Farina, Laura

AU - Ghezzi, Daniele

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