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Diffusion tensor imaging (DTI) is reported for the first time in a patient with Sjögren-Larsson syndrome, an autosomal recessive neurocutaneous disorder. Magnetic resonance spectroscopy (MRS) revealed normal levels of choline, creatine and N-acetyl aspartate (NAA) and the characteristic lipid signals in the white matter brain tissue. Conventional MRI showed increased signal intensity around the lateral ventricles indicating abnormal myelination. DTI revealed normal apparent diffusion coefficient (ADC) values, but reduced fractional anisotropy (FA) in the white matter. After co-registration of the parameters obtained with DTI with the results of MRS (36 voxels), significant correlations were obtained of lipid content with FA (r=0.81), ADC (r=-0.62), choline (r=0.51), and NAA (r=0.44) (P<0.01, all). These results suggest that in Sjögren-Larsson syndrome, the white matter lipid signals originate from the neurons, with NAA and choline reflecting neuron density and myelination. The comparatively high FA/low ADC values in these lipid-rich locations, indicate a loss of diffusion in directions perpendicular to the fibers. The overall loss of FA in the white matter may reflect a loss of brain tissue water content in SLS patients compared with controls and precede the formation of atrophy.

Biochemical and developmental results of treatment of a guanidinoacetate methyltransferase (GAMT) deficient patient with a mild clinical presentation and remarkable developmental improvement after treatment are presented. Treatment with creatine (Cr) supplementation resulted in partial normalization of cerebral (measured with magnetic resonance proton spectroscopy) and plasma levels of Cr and guanidinoacetate (GAA). Addition of high dose ornithine to the treatment led to further normalization of plasma GAA, while cerebral Cr and GAA did not improve further.

Cerebral creatine and guanidinoacetate and blood and urine metabolites were studied in four patients with argininosuccinate synthetase (ASS) or argininosuccinate lyase (ASL) deficiency receiving large doses of arginine. Urine and blood metabolites varied largely. Cerebral guanidinoacetate was increased in all patients, while cerebral creatine was low in ASS and high in ASL deficiency. Because high cerebral guanidinoacetate might be toxic, lowering the arginine supplementation with additional creatine supplementation might be important.

MR spectroscopy in two patients with glutaric aciduria type I revealed reductions in the white matter N-acetylaspartate signal, in the more severe case accompanied by a loss of glutamate and the appearance of lactate signals.

MR spectroscopy in a patient with argininosuccinate lyase deficiency revealed elevated cerebral guanidinoacetate signals, indicating that the phenomenon of increased levels of this compound in brain tissue is not limited to creatine deficiencies.