Iron Metabolism Disturbance in a French Cohort of ALS Patients

Abstract

Objective. The aim of this study was to assess iron status in a cohort of amyotrophic lateral sclerosis (ALS) patients compared to controls in order to evaluate these parameters as a risk factor or a modifying factor of ALS. Methods. We collected serum iron, ferritin, transferrin, total iron-binding capacity, and transferrin saturation coefficient (TSC) from 104 ALS patients at the time of diagnosis and from 145 controls. We reported phenotypic characteristics and evolution parameters such as ALSFRS-R and forced vital capacity at diagnosis and after one year of follow-up. In a first step we compared iron status between ALS patients and controls, and then we evaluated the relation between iron status and disease evolution of ALS patients using univariate and multivariate analysis. Results. We observed increased concentrations of serum iron (P = 0.002) and ferritin (P < 0.0001) and increased TSC (P = 0.017) in ALS patients. We also showed an association between markers of iron status and high body weight loss in ALS patients. The multivariate analysis of survival highlighted a significant relation between ferritin level and disease duration (P = 0.038). Conclusion. This is the first study showing a higher concentration of serum iron in ALS patients, strengthening the involvement of a deregulation of iron metabolism in ALS.

Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation

“…The mean serum ferritin level of female healthy controls in one study13 was 190.6 ug/L, which is higher than the upper limit of iron overload. The mean serum ferritin level was reported in both genders of another study15 as 202.2 ug/L, which is higher than the iron overload for males.…”

“…Only one report13 reported the body mass index (BMI) at 22.6 kg/m 2 . The mean ALSFRS of 3 reports,13-15 was 32.5, and the mean %FVC of 2 reports13,15 was 87.8%. The DBQAS scores of studies included were 26-29 points ( Table 1 ).…”

“…This may elevate the serum ferritin levels according the mechanism of ferritin in inflammation. In 2 papers13,15 reported that the ALS-FRS and %FVC declined year after year in natural history of ALS. Ikeda et al13 also reported that the ALSFRS and %FVC rapid worsening (ALSFRS decline ≥1 point/month and annual decline of %FVC ≥30%) had significant positive association to the baseline levels of ferritin.…”

Bioavailable Trace Metals in Neurological Diseases

“…Indeed, iron serves as an important cofactor for a number of enzymes involved in pivotal biological activities altered in ALS, and the high redox active nature of iron means that it may be a major generator of the free radicals prevalent with the disease. Serum ferritin levels are higher in ALS patients versus healthy and disease controls [83] and this elevation correlates with a shorter survival time in these patients [84][85][86].…”

Targeting Mitochondrial Metal Dyshomeostasis for the Treatment of Neurodegeneration

“…ALS is associated with elevated iron, with increased iron and iron-related proteins in the serum of ALS patients [108], and elevated iron www.futuremedicine.com in motor cortex of ALS patients as detected by MRI [109][110][111]. Evidence from SOD1 mice indicates this includes elevated mitochondrial iron [112].…”