Abstract
BACKGROUND: Neuromuscular diseases (NMDs) and mitochondriopathies are rare and heterogeneous disorders. Diagnosis is often difficult and delayed, partly due to the lack of reliable biomarkers. Chitotriosidase (CHIT1) as a candidate marker for lysosomal storage diseases is elevated in Niemann pick disease type C as a prototype of this group of diseases. Most recently, a relevant role of the lysosomal pathway in mitochondriopathies has been discussed, but markers of lysosomal involvement have not been investigated. Therefore, the aim of this study was to evaluate CHIT1 concentrations in a broad spectrum of NMDs and mitochondriopathies. METHODS: CHIT1 serum concentration of 151 patients with NMD or primary mitochondriopathy was determined by enzyme-linked immunosorbent assay, and compared to 38 healthy controls and 8 patients with Niemann pick disease type C. Results were controlled for age, sex, CRP and CHIT1 polymorphism, and compared to several established markers (CK, FGF21, GDF15). RESULTS: CHIT1 levels were not altered in NMDs, but significantly increased in mitochondriopathies, within the range of Niemann-Pick patients. Compared to the established biomarkers, CHIT1 and FGF21 showed a similar diagnostic performance, while better results were found for GDF15. However, there was a tendency for higher CHIT1 concentrations in patients with central nervous system involvement (MELAS syndrome), while FGF21 and GDF15 were not relevantly altered in these patients. Consequently, a combination of biomarkers including CHIT1 provided the best overall diagnostic performance. CONCLUSIONS: Serum CHIT1 concentration is significantly elevated in mitochondriopathies compared to healthy controls and other NMD, identifying CHIT1 as potential complementary biomarker in mitochondriopathies.