Magnetic resonance imaging in phenylketonuria: reversal of cerebral white matter change.

OBJECTIVES: To investigate the extent to which the abnormalities in cerebral white matter in adolescents and adults with phenylketonuria (PKU) are reversible. METHOD: Magnetic resonance imaging (MRI) of the brain was repeated in 41 patients with PKU (age range, 14 to 49 years) after an interval (median, 9 months; range, 3 to 12 months) of dietary intervention. Scans were scored according to the extent of the white matter involvement. After an initial MRI, five patients returned to a strict low-phenylalanine diet with amino acid supplement; 21 patients started a low-protein diet (1 gm/kg) with amino acids supplement; and 15 patients made no dietary alteration. RESULTS: Scans improved in all five patients who returned to a strict low-phenylalanine diet, in 5 of the 21 patients on the low-protein diet plus amino acid supplement, and in 4 of the 15 patients who made no dietary change. There was a significant association between change in the MRI findings and in the blood phenylalanine concentration (Pearson correlation: r = 0.55; p < 0.0002) and between change in the MRI and in the phenylalanine level at the time of the second scan (r = 0.58; p < 0.0001). Improvement was seen primarily in those in whom phenylalanine levels were reduced to less than 900 mumol/L. There was no obvious change in MRI score after 3 weeks of strict phenylalanine restriction for the two adults who underwent serial scanning. CONCLUSION: The MRI changes in PKU are at least partially reversible by lowering the blood phenylalanine concentration.

Rhizomelic chondrodysplasia punctata: clinical, pathologic, and biochemical findings in two patients.

The clinical, pathologic, and biochemical features of rhizomelic chondrodysplasia punctata are described in two patients. Although both patients had clinical and radiologic similarities, one patient survived for only 13 days and the other is still alive at 8 years. The most prominent pathologic feature was the marked degenerative change in the chondrocytes from resting cartilage. Fibroblast alkyldihydroxyacetone phosphate synthase activity was markedly reduced in both patients (approximately 10% of control mean); in contrast, dihydroxyacetone phosphate acyltransferase activity was only moderately reduced (50% of control mean). Alkyl and alk-l-enyl ether (plasmalogens) levels were very low in brain and liver. The accumulation of phytanic acid observed in plasma or liver was paralleled by a reduced ability of the patients' fibroblasts to oxidize phytanic acid. Our data indicate that the genetic defect in rhizomelic chondrodysplasia punctata results in abnormalities in two apparently unrelated pathways (i.e., phytanic acid oxidation and ether lipid biosynthesis.