No abstract

No abstract

The influence of iron deposits on T2 values and the content of metabolites in the brain of three patients with DNA proved pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome) was studied. An eye-of-the-tiger sign, a typical MR finding for PKAN, was observed in two patients with the same mutation. A hypointensive lesion in a whole globus pallidus was observed in the third patient with the additional mutation. T2 values in the globus pallidus of the patients were about 40% shorter than in controls (71/48 ms in controls vs. patients), which corresponds to the increase of Fe concentration based on the ferritin basis from 17 mg for controls to 48 mg (100 g wet brain weight) in PKAN patients. 1H MR spectroscopy (MRS) has mainly been used to describe neuronal damage represented by decreased NAA (6.4 mmol vs. 9 mmol) and Cr/PCr (7.0 mmol vs. 9.8 mmol) concentrations in the basal ganglia region of the patient group to controls; MRS is much more case-sensitive and describes individual development of the disease as demonstrated in the difference between the spectra of typical PKAN patients (1, 2), and the patient (3) with atypical PKAN development. Any significant changes of metabolite concentration with the exception glutamine, glutamate and GABA were found in the white matter.

Plasma Phenylalanine Level in Dopa-Responsive DystoniaDYT5 is a condition characterized by levodopa (L-dopa) responsive dystonia (DRD) that shows childhood onset and marked diurnal fluctuation. Patients with DYT5 have heterozygous mutations in the GCH1 gene, which codes for GTP cyclohydrolase I (GTPCH), a rate-limiting enzyme in tetrahydrobiopterin (BH 4 ) synthesis. 1 BH 4 is a cofactor for aromatic amino acid hydroxylases including tyrosine hydroxylase (TH), phenylalanine hydroxylase (PAH), and tryptophan hydroxylase. 2 In patients with DYT5, production of dopamine is suppressed due to the decrease of BH 4 because TH is a rate-limiting enzyme in dopamine synthesis. The lack of BH 4 may also affect the activity of PAH, and patients with complete GTPCH deficiency show hyperphenylalaninemia. However, hyperphenylalaninemia has not been reported in patients with DYT5. 3 Therefore, we examined blood phenylalanine levels in patients with DYT5 compared with controls to determine whether the decrease of BH 4 in DYT5 affects PAH activity.Blood samples for analysis of amino acids were obtained from seven patients with DRD 4 and heterozygous mutations of GCH1, 24 patients with dopa nonresponsive dystonia (non-DRD), and 12 controls. The samples were collected in a tube containing EDTA, and plasma was obtained for analysis of phenylalanine and tyrosine levels using an auto-amino acid analyzer (HS-3000; Hitachi, Tokyo, Japan). All data are expressed as means 6 SD. The data were analyzed by analysis of variance (ANOVA) with multiple comparison using the Bonferroni method. A significant difference was defined as a P value < 0.05.The phenylalanine and tyrosine levels in the plasma of patients with DYT5, patients with non-DRD, and controls are shown in Figure 1. The phenylalanine levels in the DYT5 (81.1 6 26.6 lmol/L), non-DRD (60.5 6 14.5 lmol/L), and control (58.7 6 9.1 lmol/L) groups were all within the normal range. However, the phenylalanine level in patients with DYT5 was significantly higher than those in the other groups (P 5 0.027 by ANOVA). Multiple comparison also indicated that the level of plasma phenylalanine in patients with DYT5 was significantly higher than those in patients with non-DRD (P 5 0.043) and in controls (P 5 0.040). There was no significant difference in the plasma phenylalanine levels between patients with non-DRD and controls. There were no significant differences in plasma tyrosine levels among all the groups. BH 4 deficiency causes hyperphenylalaninemia and a decrease of dopamine production, because it suppresses the activity of PAH and TH. Patients with a homozygous mutation in the GCH1 gene are reported to show hyperphenylalaninemia, in addition to DRD. Patients with DYT5 having only a heterozygous mutation in GCH1 also show symptoms of DRD, but do not have hyperphenylalaninemia. Our results indicated that blood phenylalanine levels in patients with DYT5 are within the normal range, but are higher than those in controls, which suggests that the activity of PAH is partially affected by the decre...

No abstract

No abstract