Ndufs4 related Leigh syndrome: A case report and review of the literature.

Juan Darío Ortigoza-Escobar, Alfonso Oyarzabal, Raquel Montero, Rafael Artuch, Cristina Jou, Cecilia Jiménez, Laura Gort, Paz Briones, Jordi Muchart, Ester López-Gallardo, Sonia Emperador, Eduardo Ruiz Pesini, Julio Montoya, Belén Pérez, Pilar Rodríguez-Pombo, Belén Pérez-Dueñas

Journal: Mitochondrion 2017;28():73-8

PMID: 27079373

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Abstract

The genetic causes of Leigh syndrome are heterogeneous, with a poor correlation between the phenotype and genotype. Here, we present a patient with an NDUFS4 mutation to expand the clinical and biochemical spectrum of the disease. A combined defect in the CoQ, PDH and RCC activities in our patient was due to an inappropriate assembly of the RCC complex I (CI), which was confirmed using Blue-Native polyacrylamide gel electrophoresis (BN-PAGE) analysis. Targeted exome sequencing analysis allowed for the genetic diagnosis of this patient. We reviewed 198 patients with 24 different genetic defects causing RCC I deficiency and compared them to 22 NDUFS4 patients. We concluded that NDUFS4-related Leigh syndrome is invariably linked to an early onset severe phenotype that results in early death. Some data, including the clinical phenotype, neuroimaging and biochemical findings, can guide the genetic study in patients with RCC I deficiency.

Address: Division of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Spain; Division of Child Neurology, Fundación Hospital Asilo de Granollers, Barcelona, Spain.; Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Centro de Biología Molecular Severo Ochoa CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, IDIPAZ, Spain.; Division of Biochemistry, Sant Joan de Déu Hospital, University of Barcelona, Spain.; Division of Biochemistry, Sant Joan de Déu Hospital, University of Barcelona, Spain; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain.; Pathology, Sant Joan de Déu Hospital, University of Barcelona, Spain; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain.; Division of Inborn Errors of Metabolism-IBC, Department of Biochemistry and Molecular Genetics, Hospital Clinic, Barcelona, Spain; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain.; Division of Inborn Errors of Metabolism-IBC, Department of Biochemistry and Molecular Genetics, Hospital Clinic, Barcelona, Spain; Consejo Superior de Investigaciones Científicas (CSIC), ISCIII, Spain; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain.; Radiology, Sant Joan de Déu Hospital, University of Barcelona, Spain.; Universidad de Zaragoza, ISCIII, Spain; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain.; Division of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Spain; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain. Electronic address: [email protected].

DOI: 10.1016/j.mito.2016.04.001

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MeSH Terms: Electron Transport Complex I, Electrophoresis, Polyacrylamide Gel, Female, Humans, Infant, Newborn, Leigh Disease, NADH Dehydrogenase, Ubiquinone