Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency.

General mitochondrial trifunctional protein (TFP) deficiency leads to a wide clinical spectrum of disease ranging from severe neonatal/infantile cardiomyopathy and early death to mild chronic progressive sensorimotor poly-neuropathy with episodic rhabdomyolysis. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency resulting from the common Glu510Gln mutation usually gives rise to a moderately severe phenotype with multiorgan involvement with high morbidity and mortality. However, isolated LCHAD deficiency can also be consistent with long-term survival in patients identified and treated from an early age. We present biochemical, clinical and mutation data in 9 patients spanning the full spectrum of disease. Fibroblast acylcarnitine profiling shows good correlation with clinical phenotype using the ratio C18(OH)/(C14(OH)+C12(OH)). This ratio shows a gradation of values, from high in four patients with severe neonatal disease (2.5+/-0.8), to low in two neuromyopathic patients (0.35, 0.2). Fibroblast fatty acid oxidation flux assays also show correlation with the patient phenotype, when expressed either as percentage residual activity with palmitate or as a ratio of percentage activity of myristate/oleate (M/O ratio). Fibroblasts from four patients with severe neonatal disease gave an M/O ratio of 4.0+/-0.6 compared to 1.97 and 1.62 in two neuromyopathic patients. Specific enzyme assay of LCHAD and long-chain 3-ketothiolase activity in patient cells shows lack of correlation with phenotype. These results show that measurements in intact cells, which allow all determinative and modifying cellular factors to be present, better reflect patient phenotype. Mutation analysis reveals a number of alpha- and beta-subunit mutations. Peripheral sensorimotor polyneuropathy, often as the initial major presenting feature but usually later accompanied by episodic rhabdomyolysis, is a manifestation of mild TFP protein deficiency. The mild clinical presentation and relative difficulty in diagnosis suggest that this form of TFP is probably underdiagnosed.

The effects of phenytoin and sodium valproate on the periodontal health of adult epileptic patients.

The periodontal health of 30 adult epileptic patients treated with either sodium valproate or phenytoin was compared with a control group (n = 15) of otherwise healthy patients. The 3 groups were matched for age and sex. Patients on phenytoin therapy showed significantly higher plaque scores (P less than 0.05), gingival index (P less than 0.05) and pocketing (P less than 0.05) than patients in the control group. The % of gingival hyperplasia was significantly higher (P less than 0.05) in the phenytoin-treated patients than those on sodium valproate or in the control group. However, patients on phenytoin therapy had significantly less bone loss than those on sodium valproate (P less than 0.05) or in the control group (P less than 0.01). No significant differences were observed between the sodium valproate group and the control group on any of the parameters assessed. The results from this study would suggest that sodium valproate has no unwanted effects on periodontal health and may be considered a safe alternative, regarding the periodontal aspects, to phenytoin for the treatment of adult onset epilepsy.