Universität zu Köln

Lehtonen, Jenni M., Forsstrom, Saara ORCID: 0000-0003-1610-6793, Bottani, Emanuela ORCID: 0000-0003-1217-8722, Viscomi, Carlo, Baris, Olivier R., Isoniemi, Helena, Hockerstedt, Krister, Osterlund, Pia, Hurme, Mikko ORCID: 0000-0002-8614-1044, Jylhava, Juulia ORCID: 0000-0003-0250-4491, Leppa, Sirpa ORCID: 0000-0002-8265-511X, Markkula, Ritva, Helio, Tiina, Mombelli, Giuliana, Uusimaa, Johanna, Laaksonen, Reijo, Laaksovirta, Hannu, Auranen, Mari, Zeviani, Massimo ORCID: 0000-0002-9067-5508, Smeitink, Jan, Wiesner, Rudolf J., Nakada, Kazuto, Isohanni, Pirjo and Suomalainen, Anu (2016). FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders. Neurology, 87 (22). S. 2290 - 2300. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1526-632X

Full text not available from this repository.

Abstract

Objective: To validate new mitochondrial myopathy serum biomarkers for diagnostic use. Methods: We analyzed serum FGF21 (S-FGF21) and GDF15 from patients with (1) mitochondrial diseases and (2) nonmitochondrial disorders partially overlapping with mitochondrial disorder phenotypes. We (3) did a meta-analysis of S-FGF21 in mitochondrial disease and (4) analyzed S-Fgf21 and skeletal muscle Fgf21 expression in 6 mouse models with different muscle-manifesting mitochondrial dysfunctions. Results: We report that S-FGF21 consistently increases in primary mitochondrial myopathy, especially in patients with mitochondrial translation defects or mitochondrial DNA (mtDNA) deletions (675 and 347 pg/mL, respectively; controls: 66 pg/mL, p<0.0001 for both). This is corroborated in mice (mtDNA deletions 1,163 vs 379 pg/mL, p<0.0001). However, patients and mice with structural respiratory chain subunit or assembly factor defects showed low induction (human 335 pg/mL, p<0.05; mice 335 pg/mL, not significant). Overall specificities of FGF21 and GDF15 to find patients with mitochondrial myopathy were 89.3% vs 86.4%, and sensitivities 67.3% and 76.0%, respectively. However, GDF15 was increased also in a wide range of nonmitochondrial conditions. Conclusions: S-FGF21 is a specific biomarker for muscle-manifesting defects of mitochondrial translation, including mitochondrial transfer-RNA mutations and primary and secondary mtDNA deletions, the most common causes of mitochondrial disease. However, normal S-FGF21 does not exclude structural respiratory chain complex or assembly factor defects, important to acknowledge in diagnostics. Classification of evidence: This study provides Class III evidence that elevated S-FGF21 accurately distinguishes patients with mitochondrial myopathies from patients with other conditions, and FGF21 and GDF15 mitochondrial myopathy from other myopathies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lehtonen, Jenni M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Forsstrom, Saara UNSPECIFIED orcid.org/0000-0003-1610-6793 UNSPECIFIED Bottani, Emanuela UNSPECIFIED orcid.org/0000-0003-1217-8722 UNSPECIFIED Viscomi, Carlo UNSPECIFIED UNSPECIFIED UNSPECIFIED Baris, Olivier R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Isoniemi, Helena UNSPECIFIED UNSPECIFIED UNSPECIFIED Hockerstedt, Krister UNSPECIFIED UNSPECIFIED UNSPECIFIED Osterlund, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hurme, Mikko UNSPECIFIED orcid.org/0000-0002-8614-1044 UNSPECIFIED Jylhava, Juulia UNSPECIFIED orcid.org/0000-0003-0250-4491 UNSPECIFIED Leppa, Sirpa UNSPECIFIED orcid.org/0000-0002-8265-511X UNSPECIFIED Markkula, Ritva UNSPECIFIED UNSPECIFIED UNSPECIFIED Helio, Tiina UNSPECIFIED UNSPECIFIED UNSPECIFIED Mombelli, Giuliana UNSPECIFIED UNSPECIFIED UNSPECIFIED Uusimaa, Johanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Laaksonen, Reijo UNSPECIFIED UNSPECIFIED UNSPECIFIED Laaksovirta, Hannu UNSPECIFIED UNSPECIFIED UNSPECIFIED Auranen, Mari UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeviani, Massimo UNSPECIFIED orcid.org/0000-0002-9067-5508 UNSPECIFIED Smeitink, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakada, Kazuto UNSPECIFIED UNSPECIFIED UNSPECIFIED Isohanni, Pirjo UNSPECIFIED UNSPECIFIED UNSPECIFIED Suomalainen, Anu UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-255356
DOI:	10.1212/WNL.0000000000003374
Journal or Publication Title:	Neurology
Volume:	87
Number:	22
Page Range:	S. 2290 - 2300
Date:	2016
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1526-632X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH; MICE; DISEASE; DEFICIENCY; ACTIVATION; MUTATIONS; DELETIONS; MYOPATHY; TWINKLE; OBESITY Multiple languages Clinical Neurology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25535