DOI: 10.7910/dvn/3hbz15
title: Prevalence and Frequency of Amyotrophic Lateral Sclerosis with C9orf72 and SOD1 Genetic Variants

description: &lt;p&gt;&lt;strong&gt;Introduction:&lt;/strong&gt; ALS or Amyotrophic lateral sclerosis, is a rare neurological disorder characterized by the progressive deterioration of motor neurons. Assessment of the size/geographic distribution of the ALS population, including ALS with the genetic origin, is needed to understand the burden of the disease and the need for clinical intervention and therapy.&lt;/p&gt;

&lt;p&gt;&lt;strong&gt;Objectives of research: &lt;/strong&gt;The main focus of this study was to evaluate ALS in 22 countries across:&lt;/p&gt;

&lt;ul&gt;
 &lt;li&gt;Europe (Belgium, France, Germany, Ireland, Italy, Netherlands, Norway, Russia, Spain, Sweden, and United Kingdom)&lt;/li&gt;
 &lt;li&gt;North America (USA and Canada)&lt;/li&gt;
 &lt;li&gt;Latin America (Argentina, Brazil, Colombia, Mexico, and Uruguay)&lt;/li&gt;
 &lt;li&gt;Asia (China, Japan, South Korea, and Taiwan).&lt;/li&gt;
&lt;/ul&gt;

&lt;p&gt;The research helps To estimate the number of prevalent and incident ALS cases overall and superoxide dismutase 1 (SOD1) and chromosome 9 open reading frame 72 (C9orf72) &lt;/p&gt;

&lt;p&gt;&lt;strong&gt;Methods of data collection:&lt;/strong&gt; A detailed literature search was conducted to identify population-based studies reporting ALS prevalence and incidence rates in each of the aforementioned countries. Pooled prevalence and incidence rates were obtained using a meta-analysis approach at the country and regional geographic levels. A country-level pooled estimate was used when &ge;3 studies were available per country, and geographic regional pooled estimates were used otherwise. The proportion of cases with a C9orf72 or SOD1 mutation among sporadic (sALS) and familial (fALS) cases were obtained from a previous systematic review and meta-analysis.&lt;br /&gt;
Results from Study: Pooled prevalence rates (per 100,000 persons) and incidence rates (per 100,000 person-years) were 7.23 and 3.21 for Europe, 6.22 and 2.85 for North America, 3.91 and 1.45 for Latin America, 4.01 and 0.97 for Asian countries (excluding Japan). The rates were 7.86 and 1.46 for Japan. Significant reported incidence and prevalence heterogeneity was observed within and between countries/geographic regions. The estimated number of 2021 ALS cases across the 22 countries is 124,028 prevalent and 44,128 incident cases. The total estimated number of general SOD1 cases is 2,976 cases, of which 1,352 (48%) were fALS and 1,524 (52%) were sALS, and the number of incident SOD1 cases is 956 (433 [45%] fALS and 522 [51%] sALS). The total estimated number of prevalent C9orf72 cases is 4,565 (1,398 [27%] fALS, 3,357 [75%] sALS), and the number of incident C9orf72 cases is 1,606 (451 [25%] fALS and 1,246 [71%] sALS).&lt;/p&gt;

&lt;p&gt;&lt;strong&gt;Discussion and additional notes&lt;/strong&gt;: The estimated number of patients with C9orf72 and SOD1 ALS suggests that although the proportions of SOD1 and C9orf72 are higher among those with fALS, the majority of SOD1 and C9orf72 ALS cases may be found among those with sALS (about 52 and 75%, respectively). These results suggest that the classification of fALS based on reported family history does not capture the complete picture of ALS of genetic origin.&lt;/p&gt;
description: Our results confirm the major role of expanded repeats in C9ORF72 as causative for ALS and provide evidence for specific phenotypic aspects compared to patients with other ALS-related genes.