An abnormally elevated level of resting energy expenditure (REE, measured by indirect calorimetry) has been reported in a subset of patients with sporadic amyotrophic lateral sclerosis (SALS). Hypermetabolism (measured REE/calculated REE (cREE)> or =1.1, or 110%) has also been observed in transgenic mice harbouring ALS-causing mutations in the SOD1 gene. By contrast, the REE of patients with familial amyotrophic lateral sclerosis (FALS) has never been assessed. Our objective was to evaluate the metabolic and nutritional parameters of FALS patients and to compare them with those of SALS patients, and search for correlations with clinical parameters. Eleven patients with FALS (from 10 different families, none carrying a SOD1 mutation) were evaluated by indirect calorimetry in our centre. As a control group, we used a sample of 33 patients with SALS, matched for age and sex with the FALS patients. 11/11 (100%) patients with FALS were hypermetabolic, compared to 17/33 (52%) patients with SALS (p=0.009). Measured REE (mREE) and mREE/cREE (metabolic level) were significantly higher in FALS patients than in SALS patients (p=0.03 and p=0.0008, respectively). No correlation was found between metabolic measures and neurological or respiratory parameters. In conclusion, hypermetabolism appears to be a common feature of subjects with FALS, suggesting that this impairment of energy homeostasis may be genetically driven. The high metabolic level of FALS patients should be taken into account for their nutritional management (need for a high-energy diet to prevent malnutrition).

Research from JAMA Neurology — Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Type 2 Caused by Mitofusin 2 Mutations

Background. Verapamil (VER), a potent calcium channel blocker, has been found to overcome P-gp-mediated multidrug resistance (MDR) and to increase sens

Objective: Severe early-onset axonal neuropathy (SEOAN) is a heterogeneous phenotype first delineated by Ouvrier et al., characterized by progressive axonal degeneration with gait problems often progressing to wheelchair requirement and later respiratory involvement. Most cases are sporadic single cases. Some have heterozygous mitofusin 2 (MFN2) mutations, many of which are de novo dominant mutations. The aim of this study was to investigate the mode of inheritance in three individuals with severe early-onset axonal neuropathy and homozygous or compound heterozygous MFN2 mutations. Methods: The clinical and molecular findings in the parents of three individuals with SEOAN with homozygous or compound heterozygous MFN2 mutations were examined. Results: All parents were asymptomatic or mildly symptomatic with some signs of peripheral neuropathy indicating a minimal phenotype. Two had hearing problems. All parents carried the relevant single base (heterozygous) MFN2 variations. Conclusion: Severe early-onset axonal neuropathy due to MFN2 mutations can present as an apparently recessively inherited neuropathy but the minimal phenotype in the parents suggests a semi-dominant mechanism.