The transverse T2-weighted image of the brain, showing extensive abnormalities of the cerebral hemispheric white matter in the patient (A), as compared with that of a normal individual (B).

The first and second rows show proton MR spectra of cerebral white matter of the patient and a control individual, respectively. The third and fourth rows show spectra of pure solutions of 50 mM D-arabitol and ribitol, respectively. The spectra on the left were obtained with a short echo time (STEAM, repetition time 6,000 milliseconds, echo time 20 milliseconds); the spectra on the right were obtained with a longer echo time (PRESS, repetition time 3,000 milliseconds, echo time 135 milliseconds). The spectra of the patient and the control individual were plotted on the same vertical scale to allow a qualitative comparison. The spectra of the D-arabitol and ribitol solutions were plotted on the same vertical scale. Note the high peaks between 3.6 and 3.8 ppm in the short-echo-time spectrum of the patient, not present in the control individual. With a longer echo time, a part of these peaks is below the baseline, related to so-called J-coupling effects. D-arabitol and ribitol are represented by resonances between 3.6 and 3.8 ppm. Comparing the short- and long-echo-time spectra, the same effects of J-coupling are seen again, in particular in D-arabitol. These data indicate that the resonances between 3.6 and 3.8 ppm in the patient can be ascribed to D-arabitol and, to a lesser extent, ribitol. For further comments on the spectral changes in the patient, see van der Knaap et al. (1999b). Ara = D-arabitol; Rib = ribitol; Cho = choline-containing compounds; Cr = total creatine; NAA = N-acetylaspartate; Lac = lactate; mIns = myoinositol.

Schematic representation of the presumed reactions leading to the formation of the pentitols ribitol, D-arabitol, and xylitol

Combined activities of RPI and RPE in cultured fibroblast homogenates, measured by monitoring the combined formation of ribulose 5-phosphate and xylulose 5-phosphate from ribose-5-phosphate in three different control cell lines (unblackened bars) and in three independent experiments in the patient cell line (blackened bars). Results are expressed as the amount of the combined ribulose 5-phosphate + xylulose 5-phosphate formed during 2 h of incubation. Mean values are given; error bars indicate the SD in the results of the control cell lines.

RPI activity in cultured fibroblast homogenates, measured by LC-MS/MS by monitoring the formation of ribose-5-phosphate from 6-phosphogluconate in three different control cell lines (unblackened bars) and in three independent experiments in the patient cell line (blackened bars). Results are expressed as the amount of ribose-5-phosphate formed during 2 h of incubation. Mean values are given; error bars indicate the SD in the results of the cell lines.

RPI cDNA sequence from a control lymphoblast sample and from the patient lymphoblast sample, showing a single base-pair deletion (c.540delG) in exon 7 (A), resulting in a frameshift and premature termination of translation of the RPI protein, and a single transition, c.182C→T, in exon 4 (B), resulting in the substitution of an alanine for a valine at codon 61 (p.A61V) in the RPI protein.