Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes

Research output: Contribution to journalArticle

Abstract

Defects of the Fe/S cluster biosynthesis represent a subgroup of diseases affecting the mitochondrial energy metabolism. In the last years, mutations in four genes (NFU1, BOLA3, ISCA2 and IBA57) have been related to a new group of multiple mitochondrial dysfunction syndromes characterized by lactic acidosis, hyperglycinemia, multiple defects of the respiratory chain complexes, and impairment of four lipoic acid-dependent enzymes: α-ketoglutarate dehydrogenase complex, pyruvic dehydrogenase, branched-chain α-keto acid dehydrogenase complex and the H protein of the glycine cleavage system. Few patients have been reported with mutations in IBA57 and with variable clinical phenotype. Herein, we describe four unrelated patients carrying novel mutations in IBA57. All patients presented with combined or isolated defect of complex I and II. Clinical features varied widely, ranging from fatal infantile onset of the disease to acute and severe psychomotor regression after the first year of life. Brain MRI was characterized by cavitating leukodystrophy. The identified mutations were never reported previously and all had a dramatic effect on IBA57 stability. Our study contributes to expand the array of the genotypic variation of IBA57 and delineates the leukodystrophic pattern of IBA57 deficient patients.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Neurology
DOIs
Publication statusAccepted/In press - Oct 26 2016

Fingerprint

Phenotype
Mutation
Glycine Decarboxylase Complex H-Protein
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Ketoglutarate Dehydrogenase Complex
Thioctic Acid
Mitochondrial Diseases
Lactic Acidosis
Acute Disease
Electron Transport
Energy Metabolism
Oxidoreductases
Brain
Enzymes
Genes
Multiple Mitochondrial Dysfunctions Syndrome

Keywords

  • IBA57
  • Leukodystrophy
  • Mitochondrial disorders
  • MMDS

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

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title = "Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes",
abstract = "Defects of the Fe/S cluster biosynthesis represent a subgroup of diseases affecting the mitochondrial energy metabolism. In the last years, mutations in four genes (NFU1, BOLA3, ISCA2 and IBA57) have been related to a new group of multiple mitochondrial dysfunction syndromes characterized by lactic acidosis, hyperglycinemia, multiple defects of the respiratory chain complexes, and impairment of four lipoic acid-dependent enzymes: α-ketoglutarate dehydrogenase complex, pyruvic dehydrogenase, branched-chain α-keto acid dehydrogenase complex and the H protein of the glycine cleavage system. Few patients have been reported with mutations in IBA57 and with variable clinical phenotype. Herein, we describe four unrelated patients carrying novel mutations in IBA57. All patients presented with combined or isolated defect of complex I and II. Clinical features varied widely, ranging from fatal infantile onset of the disease to acute and severe psychomotor regression after the first year of life. Brain MRI was characterized by cavitating leukodystrophy. The identified mutations were never reported previously and all had a dramatic effect on IBA57 stability. Our study contributes to expand the array of the genotypic variation of IBA57 and delineates the leukodystrophic pattern of IBA57 deficient patients.",
keywords = "IBA57, Leukodystrophy, Mitochondrial disorders, MMDS",
author = "Alessandra Torraco and Anna Ardissone and Federica Invernizzi and Teresa Rizza and Giuseppe Fiermonte and Marcello Niceta and Nadia Zanetti and Diego Martinelli and Angelo Vozza and Daniela Verrigni and {Di Nottia}, Michela and Eleonora Lamantea and Daria Diodato and Marco Tartaglia and Carlo Dionisi-Vici and Isabella Moroni and Laura Farina and Enrico Bertini and Daniele Ghezzi and Rosalba Carrozzo",
year = "2016",
month = "10",
day = "26",
doi = "10.1007/s00415-016-8312-z",
language = "English",
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journal = "Journal of Neurology",
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T1 - Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes

AU - Torraco, Alessandra

AU - Ardissone, Anna

AU - Invernizzi, Federica

AU - Rizza, Teresa

AU - Fiermonte, Giuseppe

AU - Niceta, Marcello

AU - Zanetti, Nadia

AU - Martinelli, Diego

AU - Vozza, Angelo

AU - Verrigni, Daniela

AU - Di Nottia, Michela

AU - Lamantea, Eleonora

AU - Diodato, Daria

AU - Tartaglia, Marco

AU - Dionisi-Vici, Carlo

AU - Moroni, Isabella

AU - Farina, Laura

AU - Bertini, Enrico

AU - Ghezzi, Daniele

AU - Carrozzo, Rosalba

PY - 2016/10/26

Y1 - 2016/10/26

N2 - Defects of the Fe/S cluster biosynthesis represent a subgroup of diseases affecting the mitochondrial energy metabolism. In the last years, mutations in four genes (NFU1, BOLA3, ISCA2 and IBA57) have been related to a new group of multiple mitochondrial dysfunction syndromes characterized by lactic acidosis, hyperglycinemia, multiple defects of the respiratory chain complexes, and impairment of four lipoic acid-dependent enzymes: α-ketoglutarate dehydrogenase complex, pyruvic dehydrogenase, branched-chain α-keto acid dehydrogenase complex and the H protein of the glycine cleavage system. Few patients have been reported with mutations in IBA57 and with variable clinical phenotype. Herein, we describe four unrelated patients carrying novel mutations in IBA57. All patients presented with combined or isolated defect of complex I and II. Clinical features varied widely, ranging from fatal infantile onset of the disease to acute and severe psychomotor regression after the first year of life. Brain MRI was characterized by cavitating leukodystrophy. The identified mutations were never reported previously and all had a dramatic effect on IBA57 stability. Our study contributes to expand the array of the genotypic variation of IBA57 and delineates the leukodystrophic pattern of IBA57 deficient patients.

AB - Defects of the Fe/S cluster biosynthesis represent a subgroup of diseases affecting the mitochondrial energy metabolism. In the last years, mutations in four genes (NFU1, BOLA3, ISCA2 and IBA57) have been related to a new group of multiple mitochondrial dysfunction syndromes characterized by lactic acidosis, hyperglycinemia, multiple defects of the respiratory chain complexes, and impairment of four lipoic acid-dependent enzymes: α-ketoglutarate dehydrogenase complex, pyruvic dehydrogenase, branched-chain α-keto acid dehydrogenase complex and the H protein of the glycine cleavage system. Few patients have been reported with mutations in IBA57 and with variable clinical phenotype. Herein, we describe four unrelated patients carrying novel mutations in IBA57. All patients presented with combined or isolated defect of complex I and II. Clinical features varied widely, ranging from fatal infantile onset of the disease to acute and severe psychomotor regression after the first year of life. Brain MRI was characterized by cavitating leukodystrophy. The identified mutations were never reported previously and all had a dramatic effect on IBA57 stability. Our study contributes to expand the array of the genotypic variation of IBA57 and delineates the leukodystrophic pattern of IBA57 deficient patients.

KW - IBA57

KW - Leukodystrophy

KW - Mitochondrial disorders

KW - MMDS

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