Informe de la Fundación Del Cerebro sobre el impacto social de la esclerosis lateral amiotrófica y las enfermedades neuromusculares

Introduction

A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness.

Variable presentation of the clinical phenotype of McArdle's disease in a kindred harbouring a novel compound genotype in the muscle glycogen phosphorylase gene

We report a Spanish family with muscle glycogen phosphorylase (PYGM) deficiency (McArdle's disease) harbouring a novel compound genotype (A659D/L586P). Four individuals who had the same genotype for PYGM, showed a wide variability in the presentation of the clinical phenotype, including one patient with a restrictive respiratory pattern, which is unusual in McArdle's disease. Moreover, these patients were studied for the insertion/deletion (I/D) trait in the angiotensin converting enzyme (ACE) which has been suggested to be a strong modulator of severity in McArdle's disease. Our results indicate no association of the I/D ACE trait in this family, suggesting that other factors would be more relevant in determining the severity of the clinical presentation.     

Characterizing SOD1 mutations in Spain: The impact of genotype,age and sex in the natural history of the disease

Background and purpose

The aim of this study was to describe the frequency and distribution of SOD1 mutations in Spain, and to explore factors contributing to their phenotype and prognosis.

Methods

Seventeen centres shared data on amyotrophic lateral sclerosis (ALS) patients carrying pathogenic or likely pathogenic SOD1 variants. Multivariable models were used to explore prognostic modifiers.

Results

In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion/insertion and 1 frameshift) were found in all five exons of SOD1, including seven novel mutations. A total of 2.6% of ALS patients (including 17.7% familial and 1.3% sporadic) were estimated to carry SOD1 mutations. The frequency of this mutation varied considerably among regions, due to founder events. The most frequent mutation was p.Gly38Arg (n = 58), followed by p.Glu22Gly (n = 11), p.Asn140His (n = 10), and the novel p.Leu120Val (n = 10). Most mutations were characterized by a protracted course, and some of them by atypical phenotypes. Older age of onset was independently associated with faster disease progression (exp[Estimate] = 1.03 [0.01, 0.05], p = 0.001) and poorer survival (hazard ratio 1.05 [1.01, 1.08], p = 0.007), regardless of the underlying mutation. Female sex was independently associated with faster disease progression (exp[Estimate] = 2.1 [1.23, 3.65], p = 0.012) in patients carrying the p.Gly38Arg mutation, resulting in shorter survival compared with male carriers (236 vs. 301 months).

Conclusions

These data may help to evaluate the efficacy of SOD1 targeted treatments, and to expand the number of patients that might benefit from these treatments.