Exploring the Genetic and Clinical Landscape of ALS in Filipino Patients: A Single-Center Case Series

Topic:

Translational Research

Poster Number: 100 S

Author(s):

Ramita Karra, MD, Department of Neurology, University of California, Los Angeles, Yigit Karasozen, MD, Department of Neurology, University of California, Los Angeles, Martina Wiedau, MD, Department of Neurology, University of California, Los Angeles

Background:
Amyotrophic lateral sclerosis (ALS) exhibits significant heterogeneity across ethnic populations. Historical data from Filipino migrant cohorts in Hawaii and Guam showed a disproportionately high incidence of ALS, reaching up to 3.38 per 100,000 person-years, which is nearly double that of other ethnic groups in the same regions. Although the Filipino population remains underrepresented in recent large-scale genetic studies, SOD1 mutations are the most common genetic cause of ALS in Asian cohorts. The SOD1 (NM_000454.5) c.434T>C; p.Leu145Ser mutation has been identified as a recurrent variant in Polish ALS patients, as well as Iranian, Brazilian and American patients, underscoring the need for ancestry-specific studies.

Objective/Results:
We present four male Filipino patients (mean age 62 years, range 51-75) evaluated at our multidisciplinary ALS clinic in 2025. Two patients carried pathogenic SOD1 mutations: the first carried a p.Leu145Ser missense mutation, and the second carried an inframe p.Gly28_Pro29del deletion. Both presented with limb-onset disease, lacked a family history of ALS, and are currently receiving intrathecal tofersen. A third patient with an ALS/FTD phenotype and positive family history carried a KIF5A pathogenic missense variant at (NM_004984.4) c.3019A>G; p.Arg1007Gly and presented with dysarthria and gait abnormalities at symptom onset. The fourth patient had limb-onset ALS with no identifiable pathogenic ALS mutations or family history.

Conclusions:
This case series emphasizes the necessity of genetic testing in all ALS patients, including the Filipino population, as three out of four Filipino patients seen at our clinic harbored a pathogenic variant despite most lacking a family history. Identifying the SOD1 p.Leu145Ser mutation in a Filipino patient further contributes to our understanding of the geographical significance of this variant. Ultimately, expanding our understanding of the clinicopathologic spectrum in understudied populations will be vital for achieving global equity in ALS diagnosis and treatment, and for ensuring access to emerging targeted therapies.