Hamilton, E.M.C. (2012) Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation : Study of the phenotype and genotype and their correlation. thesis, Medicine.
Full text available on request.Abstract
Background: Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) is a rare autosomal recessive disorder with a distinctive MRI and spectroscopy pattern, characterised by slowly progressive ataxia, spasticity and dorsal column dysfunction. The disease is caused by mutations in the DARS2 gene. There is a wide clinical variation. The aim of this study was to make an inventory of the clinical severity, disease course and genotype in LBSL patients and to study the possible influence of genotype and gender on the phenotype. Methods: A cross sectional observational study in 71 patients (62 families) with two proven DARS2 mutations was conducted. Clinical information was collected through questionnaires for physicians and families. Results: The clinical course in LBSL patients varied from early onset, fatal disease up to an adult onset, mild disorder. The most common phenotype was childhood onset, slowly progressive neurological deterioration, with a normal intelligence (59%). Full wheelchair dependency was rather unusual and predominantly occurred in adulthood. 44 different DARS2 mutations were observed. Almost all patients had at least one splice-site mutation. The male-female ratio was 1:1.45. The mildest variant of the disease was observed more often in females. No genotype-phenotype correlation could be demonstrated, but because of the many different second mutations, the groups of patients with the same two mutations were too small for statistical analysis. Conclusions: This study describes the natural course and genotype in the largest cohort of LBSL patients to date. LBSL is a very heterogeneous disorder caused by numerous different mutations. Larger groups of patients are required to study the genotype-phenotype correlation.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Nijholt, Dr. I.M. and faculty supervisor |
| Supervisor name: | Knaap Prof. dr. M.S. van der (external supervisor) and Vrije Universiteit medical center, Department of Child Neuro and Center for Children with White Matter Disorders |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:39 |
| Last Modified: | 25 Jun 2020 10:39 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/116 |
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