MR spectroscopy and serial magnetic resonance imaging in a patient with mitochondrial cystic leukoencephalopathy due to complex I deficiency and NDUFV1 mutations and mild clinical course.

We present clinical, magnetic resonance imaging and MR spectroscopic findings of a female patient, first admitted at the age of 9 months for regression of motor milestones and signs of mild spastic diplegia. Magnetic resonance imaging (MRI) demonstrated periventricular white matter abnormalities with sparing of the subcortical white matter. Subsequent MRIs, performed at the ages of 13 and 16 months, demonstrated progression of the white matter changes, progressive white matter rarefaction and cystic degeneration, and additional involvement of the corpus callosum; only the subcortical white matter remained spared. Proton MR spectroscopy revealed lactate elevation in the white matter. Blood lactate and lactate/pyruvate ratio were mildly elevated. Subsequent analysis of mitochondrial function in muscle tissue showed decreases in substrate oxidation and in ATP and CrP production rates. Complex I activity was seriously decreased, whereas mild decreases of complex II and IV activities were also noted. Analysis of the NDUFV1 gene revealed compound heterozygosity for two point mutations, each of them carried by one parent. The further clinical course of the patient was uphill; she slowly regained all previously lost motor milestones. In conclusion, diffuse white matter changes on MRI are compatible with mitochondrial encephalopathy and not necessarily associated with a severe clinical course.