Researchers at VU University Medical Center, Amsterdam and other international centers reviewed the MRIs of >3000 patients with an unclassified leukoencephalopathy, and 7 patients (3 male) shared similar MRI abnormalities and clinical and laboratory findings. Between ages 9 months and 2 years, MRIs showed signal abnormalities of deep cerebral white matter, corpus callosum, thalamus, basal ganglia, brainstem, and cerebellar white matter. A rim of periventricular white matter was preserved. At follow-up, abnormalities gradually improved. Clinical manifestations were correlated with the MRI findings. Clinical regression occurred in the second half-year of life with limb spasticity, axial hypotonia, and loss of milestones and accompanied by elevated blood and CSF lactate levels. After 2 years of age, patients showed clinical improvement and normal lactate. Lysosomal enzyme activities in leukocytes, especially arylsulfatase A and galactocerebrosidase, were normal. Acylcarnitine, amino acid, urinary organic acid, and very-long-chain fatty acid levels were normal. Mitochondrial DNA screening for mutations was negative. The patients represented a single novel leukoencephalopathy, probably caused by a mitochondrial defect. [1]

COMMENT. Metachromatic leukodystrophy, Krabbe’s disease, Alexander disease, adrenoleukodystrophy, and known mitochondrial diseases were excluded.

The first author of the above paper also reports a leukoencephalopthy with thalamus and brainstem involvement and high lactate ‘LTBL’ caused by EARS2 mutations. [2]. In a cohort of 12 patients, this mitochondrial encephalopathy was either mild or severe, with infantile onset, rapidly progressive MRI abnormalities and increased lactate. Patients in the mild group partially recovered and regained milestones at follow-up, MRI improved, and lactate levels fell toward normal. Patients in the severe group had persistent neurological regression, brain atrophy on MRI, and increased lactate. MRI was hallmarked by symmetrical cerebral white matter abnormalities sparing the periventricular rim, and symmetrical abnormalities of the thalami, brain stem, and cerebellar white matter.