Refsum's disease (hereditary motor sensory neuropathy type IV, heredopathia atactica polyneuritiformis) is an autosomal recessive disorder the clinical features of which include retinitis pigmentosa, blindness, anosmia, deafness, sensory neuropathy, ataxia and accumulation of phytanic acid in plasma-and lipid-containing tissues. The transport and biochemical pathways of phytanic acid metabolism have recently been defined with the cloning of two key enzymes, phytanoylCoA 2-hydroxylase (PAHX) and 2-hydroxyphytanoyl-CoA lyase, together with the confirmation of their localization in peroxisomes. PAHX, an iron(II) and 2-oxoglutarate-dependent oxygenase is located on chromosome 10p13. Mutant forms of PAHX have been shown to be responsible for some, but not all, cases of Refsum's disease. Certain cases have been shown to be atypical mild variants of rhizomelic chondrodysplasia punctata type 1a. Other atypical cases with lowplasma phytanic acid may be caused by a-methylacyl-CoA racemase deficiency. A sterol-carrier protein-2 (SCP-2) knockout mouse model shares a similar clinical phenotype to Refsum's disease, but no mutations in SCP-2 have been described to-date in man. This review describes the clinical, biochemical and metabolic features of Refsum's disease and shows how the biochemistry of the a-oxidation pathway may be linked to the regulation of metabolic pathways controlled by isoprenoid lipids, involving calcineurin or the peroxisomal proliferator activating a-receptor.
Summary: Purpose: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbainaLepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared.Methods: In a double-blind parallel-groups study. I X 1 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic-clonic seizures were randoniised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (ti = 95) received PHT titrated from 200 ing/tlay. Treatment continued for 5 4 8 weeks.
K i~s i d t x ;The percentages of patients remaining on each treatment and seiLure frec during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose-titration period). did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of effi safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (IS%) patients from LTG and 18 ( 1 9%) from PHT. The adverse-event profile for LTG w.as dominated by skin rash (discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effect sthenia, somnolence, and ataxia were each significantly inore frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument. the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an eiizyrneinducing drug, whereas those taking LTG did not.Cotwlusiot~.~: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, inore frequently causing rash. but with a lower incidence of central nervous system side effects.
One hundred and fifty‐one foods were analysed for phytanic acid and 57 foods for free phytol. Foods analysed included examples from all major food groups, beverages and confectionery.
No significant amount of phytanic acid was found in any food of purely vegetable origin. The sources of phytanic acid in the UK diet were confirmed to be foods derived from ruminant animals and fish. They include beef, lamb and products containing the milk fats of cows, sheep and goats. All fish were found to contain phytanic acid roughly in proportion to their fat content. Domestic and commercial fat blends containing animal fats (chiefly hydrogenated fish oils) and baked goods made from these fats contained phytanic acid: pure vegetable fat blends and foods containing them did not.
Free phytol was found in small amounts in a variety of foods but not in sufficient quantity to warrant the exclusion of any one item from the diet of patients with Refsum's disease.
Refsum's disease (MIM 266500) is a recessive disorder characterised by defective peroxisomal alpha-oxidation of phytanic acid. A Refsum's disease gene, phytanoyl-CoA hydroxylase (PAHX), has been localised to chromosome 10p13 between the markers D10S226-D10S223. This study investigated whether all cases of Refsum's disease were linked with chromosome 10p13. Eight genetically informative families comprising 92 individuals including 17 living patients with a Refsum's disease phenotype and initial plasma phytanic acid > 200 µmol/L were recruited. Linkage to the 10pter-10p11.2 region was investigated using a panel of eight dinucleotide repeat markers. Linkage analysis of this phenotypically identical cohort suggested that Refsum's disease was genetically heterogeneous (Z max = 5.28, α = 0.45). Two subgroups were identified. One group of four families with eight affected individuals had a maximum multipoint lod score for linkage of 3.89 in the region D10S547 to D10S191, whilst in another three families with nine affected individuals linkage to this region was definitely excluded. Our results show that Refsum's disease is genetically heterogeneous, with up to 55% of cases not being linked to the PAHX gene locus at D10S547 to D10S223. This suggests that Refsum's disease, in common with other peroxisomal 'diseases', may be more accurately described as a heterogeneous syndrome.
SummaryIn a series of 645 patients with epilepsy only 38 had attacks exclusively during sleep. A further 111 had attacks while waking and sleeping. The total number of patients whose epilepsy started with sleep attacks and who later developed attacks when waking increased with each successive year. The prognosis of sleep epilepsy is important in relation to the granting of driving licences.
IntroductionThe recent revision of the regulations concerning driving and
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