Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report.
BMC Neurol. 2018-10-23; 18(1):
DOI: 10.1186/s12883-018-1180-7
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1. BMC Neurol. 2018 Oct 23;18(1):175. doi: 10.1186/s12883-018-1180-7.
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related
leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation:
a case report.
Yahia A(1)(2)(3), Elsayed L(4), Babai A(5), Salih MA(6), El-Sadig SM(7)(8), Amin
M(1), Koko M(9), Abubakr R(5), Idris R(5), Taha SOMA(10), Elmalik SA(11), Brice
A(12)(3), Ahmed AE(13)(8), Stevanin G(14)(3).
Author information:
(1)Department of Biochemistry, Faculty of Medicine, University of Khartoum,
Khartoum, Sudan.
(2)Department of Biochemistry, Faculty of Medicine, National University,
Khartoum, Sudan.
(3)Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225,
Sorbonne Universités UMR_S1127, 75013, Paris, France.
(4)Department of Biochemistry, Faculty of Medicine, University of Khartoum,
Khartoum, Sudan. .
(5)Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
(6)Division of Pediatric Neurology, Department of Pediatrics, College of
Medicine, King Saud University, Riyadh, Saudi Arabia.
(7)Department of Medicine, Faculty of Medicine, University of Khartoum, Khartoum,
Sudan.
(8)Department of Neurology, Soba University Hospital, Khartoum, Sudan.
(9)Department of Neurology & Epileptology, Hertie Institute for Clinical Brain
Research, University of Tübingen, Tübingen, Germany.
(10)Department of Radiology, Dar Al Elaj specialized hospital, Khartoum, Sudan.
(11)Department of Physiology, College of Medicine, King Saud University, Riyadh,
Saudi Arabia.
(12)Department of Genetics, APHP, Pitié-Salpêtrière Hospital, Paris, France.
(13)Department of Physiology, Faculty of Medicine, University of Khartoum,
Khartoum, Sudan.
(14)Ecole Pratique des Hautes Etudes, EPHE, PSL Research University, Paris,
France.
BACKGROUND: Leukoencephalopathy with brainstem and spinal cord involvement and
lactate elevation (LBSL, OMIM #611105) is a genetic disease of the central
nervous system characterized by lower limb spasticity, cerebellar ataxia and
involvement of the dorsal column. The disease is caused by mutations in the DARS2
gene but has never been reported in sub-Saharan Africa so far.
CASE PRESENTATION: Two siblings, aged 18 years and 15 years, from a
consanguineous family presented with pyramidal signs and symptoms since infancy
and developmental delay. Whole exome sequencing of the proband identified two
compound heterozygous variants (NM_018122.4:c.1762C > G and c.563G > A) in DARS2.
Sanger sequencing confirmed the presence of the mutations and their segregation
in trans in both patients and in their elder sister (aged 20 years), who showed
only brisk reflexes and mild lower limb spasticity. Surprisingly, in contrast to
her subtle clinical presentation, the elder sister had abnormal MRI features and
serum lactate levels comparable to her ill sisters.
CONCLUSION: This report illustrates intra-familial phenotypic variation in LBSL
and provides an example of a marked dissociation between the clinical and
radiological phenotypes of the disease. This may have implications for the
detection of mutation carriers in LBSL.
DOI: 10.1186/s12883-018-1180-7
PMCID: PMC6198356
PMID: 30352563 [Indexed for MEDLINE]