Cree Leukoencephalopathy (CLE) is a rapidly progressive and invariably fatal neurodegenerative disorder that affects children of Cree and Chippewayan descent. It is also referred to as Cree Leukodystrophy. It is an autosomal recessive condition with patients being homozygous for a mutation in the gene that encodes the ε subunit of the Eukaryotic Initiation Factor 2B (EIF2B5). Cree Leukoencephalopathy is allelic to Vanishing White Matter Disease, one of the most prevalent inherited white matter disorders. 1,2 Affected children become symptomatic in the first year of life usually following a mild viral infection. They undergo a rapid neurological decline with progressive spasticity and blindness leading to decerebrate posturing, obtundation and death. Magnetic resonance imaging (MRI) shows extensive, symmetric white matter loss in the brainstem and cerebrum, with involvement of the subcortical U-fibres. 3 Magnetic resonance spectroscopy (MRS) demonstrates diminished N-acetylaspartate (NAA), elevated choline and the presence of lactate peaks in keeping with the breakdown of myelin and physiological stress. 1 Affected children also have a peripheral neuropathy involving the large myelinated sensory fibres similar to that seen in metachromatic leukodystrophy. 1 Recently, a two-year-old male sibling of two children who died of CLE was investigated for recurrent seizures arising from the right hemisphere. Genetic studies showed that he was a heterozygous carrier for CLE. His MRI was normal, however MRS with multivoxel Point Resolved Spectroscopy (PRESS) acquisition (TRE/TE=3000/144msec) obtained at the level of the corona radiata showed many voxels within the right frontal white matter to have diminished NAA/creatine and elevated choline/creatine ratios. Lactate peaks were not identified. Manifesting heterozygotes have been reported in various autosomal recessive neurological conditions such as Giant axonal neuropathy, McCardle disease and carnitine palmitoyltransferase deficiency type II. In general, they have much milder symptoms when compared to homozygotes. 4-6 The presence of an abnormal MRS in our patient raised the possibility that manifesting heterozygotes could occur among CLE carriers. The presence of detectable changes in the nervous systems of EIF2B mutation carriers has not been previously assessed in a systematic manner. We decided to test this hypothesis by inviting known adult CLE carriers to undergo a formal neurological assessment, nerve conduction studies and MRI/MRS.