Quantifying Disease Progression in LBSL

Overview

Leukoencephalopathy with brain stem involvement and lactate elevation (LBSL) is a genetic disorder caused by biallelic mutations in the DARS2 gene that encodes mitochondrial aspartyl tRNA synthase.(1, 2) It is characterized by typical abnormalities on MRI of the brain and spinal cord.(3) Clinically, the disorder is heterogeneous and can present in the neonatal period, later in childhood or even in adults.(3) In general it can be stated that the earlier presentations are characterized by rapid progression leading to severe disability and death. Presentation at a later age is typically characterized by a more benign disease course, although considerable disability is common. Clinically, the disease presents as a slowly progressive myelopathy with mainly involvement of the corticospinal tracts and the dorsal columns. Although the natural history has been studied in large cohorts, the rate of progression has not been systematically studied with clinimetric outcome scales or potential surrogate outcomes for spinal cord disease.

Eligibility

In order to be eligible to participate in this study, a subject must meet all of the

following criteria:

• Age > 16 years
• Definite diagnosis of LBSL confirmed by DARS2 mutation analysis.
• Able to understand Dutch or English and provide informed consent.
• No contra-indications for MRI of brain and spinal cord.

        Subjects eligible to participate as healthy controls must meet all of the following
        criteria:
          -  Willing to visit the hospital
          -  16 years or older
          -  Provision of written informed consent to participate in the study obtained from the
             participant
        For the MRI controls:
        - No contra-indications for MRI of the brain and spinal cord
        A potential subject (patient or healthy control) who meets any of the following criteria
        will be excluded from participation in this study:
          -  Unable to visit the hospital for the follow-up visits
          -  Co-existing neurological disease that can cause pyramidal tract signs making
             interpretation of acquired data difficult (for instance, multiple sclerosis, stroke,
             etc)