Natural History Study of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL)
Natural History Study of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL)
In this study, we will conduct retrospective chart and imaging reviews and prospective
 longitudinal virtual assessments of individuals with LBSL.
LBSL (leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation)
 is a rare genetic disorder characterized by slowly progressive cerebellar ataxia and
 spasticity with dorsal column dysfunction (decreased position and vibration sense) in most
 patients. Manual dexterity becomes impaired to a variable degree. Associated problems include
 dysarthria, mild cognitive decline and learning problems, and epilepsy. LBSL is diagnosed by
 identification of biallelic pathogenic variants in DARS2, encoding mitochondrial aspartyl
 tRNA synthetase and characteristic abnormalities observed on the brain and spinal cord MRI.
 Most of the literature consists of case reports and case series and there are only limited
 data that provide details on genotype-phenotype correlations. There is very little
 quantitative or semi-quantitative information about neurocognitive and neuromotor impairment
 in LBSL. There are currently no targeted therapies or guidelines about supportive therapies
 for LBSL.

 In this study, we will conduct retrospective chart and imaging reviews and prospective
 longitudinal virtual assessments of individuals with LBSL.

 We hypothesize that 1) there will be a broad phenotypic spectrum of neuromotor and
 neurocognitive deficits in LBSL patients; 2) most impairment will likely be related to gait;
 3) there will be a threshold of impairment in gait that is associated with poorer quality of
 life for these patients; 4) and that even in patients with apparently mild disease there will
 be neurocognitive deficits related to cortical and cerebellar white matter abnormalities.

 Answering these hypotheses will form the basis of a better understanding of the natural
 history of LBSL. It will help further characterize the expected level of impairment based on
 a patient's genotype. This will be particularly helpful for providing anticipatory guidance
 for newly diagnosed infants and children with LBSL. The information will also help identify
 priorities for existing supportive therapies and help clarify the common or clinically
 meaningful symptoms that should be targeted for new treatments.
Inclusion Criteria:

 1. Confirmed DARS2 mutation through genetic analysis

 2. Ability of the caregiver or participant to speak and understand English at an
 8th-grade level

 Exclusion Criteria:

 -  The vulnerable populations of prisoners, non-viable neonates, pregnant women, adults
 lacking the capacity to consent, non-English speakers or children who are in foster
 care or wards of the state.