Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Leukoencephalopathy due to Complex II Deficiency and Bi-Allelic SDHB Mutations: Further Cases and Implications for Genetic Counselling

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Genotype and phenotype classification of 29 patients affected by Krabbe disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Impaired fat oxidation during exercise in multiple acyl-CoA dehydrogenase deficiency

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Diagnostic pitfalls in vitamin B6-dependent epilepsy caused by mutations in the PLPBP gene

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Cognitive Impairments and Subjective Cognitive Complaints in Fabry Disease: A Nationwide Study and Review of the Literature

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Danish expanded newborn screening is a successful preventive public health programme

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Osmotisk demyeliniseringssyndrom

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Hydroxylated Long-Chain Acylcarnitines are Biomarkers of Mitochondrial Myopathy

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Isolated complex II deficiency is a rare cause of mitochondrial disease and bi-allelic mutations in SDHB have been identified in only a few patients with complex II deficiency and a progressive neurological phenotype with onset in infancy. On the other hand, heterozygous SDHB mutations are a well-known cause of familial paraganglioma/pheochromocytoma and renal cell cancer. Here, we describe two additional patients with respiratory chain deficiency due to bi-allelic SDHB mutations. The patients' clinical, neuroradiological, and biochemical phenotype is discussed according to current knowledge on complex II and SDHB deficiency and is well in line with previously described cases, thus confirming the specific neuroradiological presentation of complex II deficiency that recently has emerged. The patients' genotype revealed one novel SDHB mutation, and one SDHB mutation, which previously has been described in heterozygous form in patients with familial paraganglioma/pheochromocytoma and/or renal cell cancer. This is only the second example in the literature where one specific SDHx mutation is associated with both recessive mitochondrial disease in one patient and familial paraganglioma/pheochromocytoma in others. Due to uncertainties regarding penetrance of different heterozygous SDHB mutations, we argue that all heterozygous SDHB mutation carriers identified in relation to SDHB-related leukoencephalopathy should be referred to relevant surveillance programs for paraganglioma/pheochromocytoma and renal cell cancer. The diagnosis of complex II deficiency due to SDHB mutations therefore raises implications for genetic counselling that go beyond the recurrence risk in the family according to an autosomal recessive inheritance.

Original languageEnglish
JournalJIMD Reports
Volume33
Pages (from-to)69-77
ISSN2192-8304
DOIs
Publication statusPublished - 2017

ID: 49195000