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AARS2‐related ovarioleukodystrophy: Clinical and neuroimaging features of three new cases
Author(s) -
Taglia I.,
Di Donato I.,
Bianchi S.,
Cerase A.,
Monti L.,
Marconi R.,
Orrico A.,
Rufa A.,
Federico A.,
Dotti M. T.
Publication year - 2018
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.12954
Subject(s) - leukodystrophy , leukoencephalopathy , corpus callosum , pathology , medicine , white matter , compound heterozygosity , magnetic resonance imaging , mutation , biology , radiology , genetics , gene , disease
Introduction Adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia ( ALSP ), previously known as hereditary diffuse leukoencephalopathy with axonal spheroids ( HDLS ) or pigmentary orthochromatic leukodystrophy ( POLD ), is the most frequent non‐vascular adult‐onset leukoencephalopathy. It is caused by autosomal dominant mutations in CSF 1R gene. Recently, also autosomal recessive mutations in AARS 2 gene were found to be the cause of an adult‐onset leukodystrophy with axonal spheroids. Our aim was to achieve a genetic diagnosis in a cohort of CSF 1R‐ negative patients, performing a sequence analysis of AARS 2 gene. Material and Methods AARS 2 sequencing was performed in 38 CSF 1 R‐negative patients with clinical and magnetic resonance imaging (MRI) findings of adult‐onset leukoencephalopathy. Results Three patients carrying AARS 2 compound heterozygous mutations have been found. All patients were female with ovarian failure and leukoencephalopathy. In 2 patients, MRI findings were consistent with previous reports while the third patient showed focal white matter ( WM ) lesions in the centrum semiovale and the corpus callosum in the absence of extensive involvement and rarefaction of the WM . MRI spectroscopy showed the presence of increased lactate in 2 patients, thus linking AARS 2 ‐related leukoencephalopathy with other mitochondrial leukoencephalopathies with high levels of cerebral lactate. Conclusion We recommend screening for mutations in AARS 2 gene in CSF 1R‐ negative patients, also in the absence of a clear family history and peculiar MRI findings. Our results also suggest that findings of conventional MRI and MR spectroscopy may be useful in prompting the genetic screening.