A Guideline for the Diagnosis of Pediatric Mitochondrial Disease: The Value of Muscle and Skin Biopsies in the Genetics Era

Wortmann, Saskia; Mayr, Johannes; Nuoffer, Jean-Marc; Prokisch, Holger; Sperl, Wolfgang (2017). A Guideline for the Diagnosis of Pediatric Mitochondrial Disease: The Value of Muscle and Skin Biopsies in the Genetics Era. Neuropediatrics, 48(04), pp. 309-314. Thieme 10.1055/s-0037-1603776

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Mitochondrial diseases are highly hetero geneous on the clinical, biochemical, and genetic level. In the traditional diagnostic approach (“biopsy first”) the evaluation of the affected individual and his body fluids, combined with the analysis of the respiratory chain enzymes in muscle based the subsequent Sanger sequencing of single candidate genes (“from function to gene”). Within the past few years, next-generation sequencing techniques of leucocyte-derived DNA (e.g., exome sequencing), with a diagnostic yield of more than 40%, have become the first line routine technology. This implicates that the invasive muscle biopsy is performed less often, especially in children. Furthermore, in this “genetics-first” approach the detection of new candidate genes precedes functional evaluations (“from gene to function”) leading to reverse phenotyping of affected individuals. Here, we line out the value of muscle and other tissue biopsies in this “genetics-first” era. We describe when and why it is still needed. We create awareness of pitfalls in the genetic diagnostics of mitochondrial diseases still necessitating tissue biopsies. Finally, we discuss why tissue biopsies are required for confirmatory diagnostics, or for getting a biochemical diagnosis in patients with hidden variants not detectable by standard genetics.

Item Type:

Journal Article (Review Article)


04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Nuoffer, Jean-Marc


600 Technology > 610 Medicine & health








Jean-Marc Nuoffer

Date Deposited:

06 Mar 2018 15:30

Last Modified:

22 Oct 2019 18:54

Publisher DOI:


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