Magnetic resonance imaging and genetic investigation of a case of rottweiler leukoencephalomyelopathy

Katrin Hirschvogel,Katharina Flatz,Bärbel Reiner,Kaspar Matiasek,Michaela Drögemüller,Andrea Fischer,Cord Drögemüller

doi:10.1186/1746-6148-9-57

Katrin Hirschvogel, Katharina Flatz + Show 5 more

Open Access

https://doi.org/10.1186/1746-6148-9-57

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Abstract

BackgroundLeukoencephalomyelopathy is an inherited neurodegenerative disorder that affects the white matter of the spinal cord and brain and is known to occur in the Rottweiler breed. Due to the lack of a genetic test for this disorder, post mortem neuropathological examinations are required to confirm the diagnosis. Leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate levels is a rare, autosomal recessive disorder in humans that was recently described to have clinical features and magnetic resonance imaging (MRI) findings that are similar to the histopathologic lesions that define leukoencephalomyelopathy in Rottweilers. Leukoencephalopathy with brain stem and spinal cord involvement is caused by mutations in the DARS2 gene, which encodes a mitochondrial aspartyl-tRNA synthetase. The objective of this case report is to present the results of MRI and candidate gene analysis of a case of Rottweiler leukoencephalomyelopathy to investigate the hypothesis that leukoencephalomyelopathy in Rottweilers could serve as an animal model of human leukoencephalopathy with brain stem and spinal cord involvement.Case presentationA two-and-a-half-year-old male purebred Rottweiler was evaluated for generalised progressive ataxia with hypermetria that was most evident in the thoracic limbs. MRI (T2-weighted) demonstrated well-circumscribed hyperintense signals within both lateral funiculi that extended from the level of the first to the sixth cervical vertebral body. A neurodegenerative disorder was suspected based on the progressive clinical course and MRI findings, and Rottweiler leukoencephalomyelopathy was subsequently confirmed via histopathology. The DARS2 gene was investigated as a causative candidate, but a sequence analysis failed to identify any disease-associated variants in the DNA sequence.ConclusionIt was concluded that MRI may aid in the pre-mortem diagnosis of suspected cases of leukoencephalomyelopathy. Genes other than DARS2 may be involved in Rottweiler leukoencephalomyelopathy and may also be relevant in human leukoencephalopathy with brain stem and spinal cord involvement.

Highlights

Leukoencephalomyelopathy is an inherited neurodegenerative disorder that affects the white matter of the spinal cord and brain and is known to occur in the Rottweiler breed
It was concluded that magnetic resonance imaging (MRI) may aid in the pre-mortem diagnosis of suspected cases of leukoencephalomyelopathy
Genes other than DARS2 may be involved in Rottweiler leukoencephalomyelopathy and may be relevant in human leukoencephalopathy with brain stem and spinal cord involvement

Summary

Conclusion

Magnetic resonance imaging has become the primary tool for the ante mortem diagnosis of white matter disease in humans due to its high sensitivity for detecting changes in white matter. MR spectroscopy demonstrates an elevation in lactate levels in the abnormal white matter of almost all of the affected human patients These findings led researchers to assume that the disease was a mitochondrial disorder, which was subsequently confirmed by the discovery of various mutations in the DARS2 gene, which encodes mitochondrial aspartyltRNA synthetase [14,38]. Further limitations of our case report include the lack of pedigree analysis and brain lactate MR spectroscopy measurements and the failure of MR to demonstrate the involvement of the cerebrum despite the pathology observed in histological sections Another limitation is that the comparison of the pathologies of these diseases in dogs and humans is limited by the paucity of case data from both.

Background

35. Renaud DL