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Alsin related disorders: literature review and case study with novel mutations

Filipa Flor-de-Lima1, Mafalda Sampaio2, Nahid Nahavandi3

  • 1Department of Pediatrics, Hospital Pediátrico Integrado, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal ; Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.

Case Reports in Genetics
|October 11, 2014
PubMed

Insights

Mutations in the ALS2 gene cause rare neurological disorders. This study details a new case of infantile ascending hereditary spastic paraplegia and reviews 42 others, highlighting overlapping symptoms in related ALS2 gene disorders.

Area of Science:

  • Genetics and Neurology
  • Rare Disease Research

Background:

  • Mutations in the ALS2 gene are linked to infantile ascending hereditary spastic paraplegia (IAHSP), juvenile primary lateral sclerosis (JPLS), and autosomal recessive juvenile amyotrophic lateral sclerosis (ARJALS).
  • Phenotypic variability and overlap among these ALS2-related disorders are not fully understood.

Purpose of the Study:

  • To report the first Portuguese case of IAHSP in a 16-year-old male.
  • To analyze the clinical, neurophysiological, and imaging characteristics of patients with known ALS2 gene mutations.
  • To investigate the overlap in phenotypic manifestations across IAHSP, JPLS, and ARJALS.

Main Methods:

  • Literature review of 42 reported cases with ALS2 gene mutations from PubMed.
  • Clinical investigation of a 16-year-old patient, including ALS2 gene sequencing.
  • Analysis of clinical characteristics, neurophysiological data, and imaging studies.

Main Results:

  • A novel heterozygous variant (c.145G>A p.G49R) and a known heterozygous mutation (c.1425_1428del p.G477Afs*19) in the ALS2 gene were identified in the patient.
  • The study identified significant overlap in clinical symptoms among patients with IAHSP, JPLS, and ARJALS.
  • Neurophysiological and imaging findings showed considerable variability within and across the different ALS2-related phenotypes.

Conclusions:

  • The ALS2 gene is a significant factor in a spectrum of early-onset motor neuron diseases.
  • Genetic analysis and comprehensive clinical evaluation are crucial for diagnosing ALS2-related disorders.
  • Further research is needed to elucidate the genotype-phenotype correlations and mechanisms underlying symptom overlap in ALS2 gene mutations.

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