Juvenile Amyotrophic Lateral Sclerosis: A Review

Abstract

Juvenile amyotrophic lateral sclerosis (JALS) is a rare group of motor neuron disorders with gene association in 40% of cases. JALS is defined as onset before age 25. We conducted a literature review of JALS and gene mutations associated with JALS. Results of the literature review show that the most common gene mutations associated with JALS are FUS, SETX, and ALS2. In familial cases, the gene mutations are mostly inherited in an autosomal recessive pattern and mutations in SETX are inherited in an autosomal dominant fashion. Disease prognosis varies from rapidly progressive to an indolent course. Distinct clinical features may emerge with specific gene mutations in addition to the clinical finding of combined upper and lower motor neuron degeneration. In conclusion, patients presenting with combined upper and lower motor neuron disorders before age 25 should be carefully examined for genetic mutations. Hereditary patterns and coexisting features may be useful in determining prognosis.

Keywords: ALS2; FUS; SETX; familial amyotrophic lateral sclerosis; motor neuron disease.

Figure 1

(a) Literature search in PubMed. (b) Literature search in EMBASE.

Figure 2

Function and localization of proteins from genes with JALS-associated mutations. Figure legend: Function and localization of proteins from genes with JALS-associated mutations. Proteins are represented as gray circles. GNE, SPTLC1, and DDHD1 function in the metabolism of N-acetylneuraminic acid, sphingolipid, and glycerophospholipid, respectively. FUS: fused in sarcoma; SETX: senataxin; SIGMAR1: sigma-1 receptor; SOD1: copper/zinc superoxide dismutase-1; SPTLC1: serine palmitoyltransferase; long-chain base subunit 1; UBQNL2: ubiquilin 2; VRK1: vaccinia-related kinase 1; ERLIN1: endoplasmic reticulum lipid raft-associated protein 1; GNE: glucosamine (UDP-N-acetyl)-2-epimerase; TARDBP: TAR DNA binding protein; SYNE1: spectrin repeat containing nuclear envelope protein 1 gene; BICD2: BICD cargo adaptor 2 gene; and DDHD1: DDHD domain containing 1.