Loretta Racis1, Alessandra Tessa2, Maura Pugliatti3, Eugenia Storti2, Virgilio Agnetti3, Filippo M Santorelli4. 1. Department of Clinical and Experimental Medicine, Sassari, Italy; Department of Biomedical Sciences, University of Sassari, Sassari, Italy. 2. IRCCS Stella Maris, Pisa, Italy. 3. Department of Clinical and Experimental Medicine, Sassari, Italy. 4. IRCCS Stella Maris, Pisa, Italy. Electronic address: filippo3364@gmail.com.
Abstract
BACKGROUND: Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a rare, early-onset autosomal recessive motor neuron disease associated with mutations in ALS2. AIM: We studied a 17-year-old boy who had features of IAHSP. We also reviewed the current literature on ALS2-related syndromes. METHODS: Clinical and neuroimaging studies were performed. Blood DNA analyses were combined with mRNA studies in cultured skin fibroblasts. RESULTS: Like previously described cases, the patient presented with severe spastic paraparesis and showed rapid progression of paresis to the upper limbs. He also developed bulbar involvement and severe scoliosis during childhood. In blood DNA we identified a novel splice-site homozygous mutation in ALS2 (c.3836+1G > T), producing exon skipping in fibroblast mRNA and predicting premature protein truncation. CONCLUSIONS: This case adds to the allelic heterogeneity of IAHSP. Review of the pertinent literature indicates a fairly homogeneous clinical picture in IAHSP that should facilitate molecular confirmation and prevention of long-term complications.
BACKGROUND: Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a rare, early-onset autosomal recessive motor neuron disease associated with mutations in ALS2. AIM: We studied a 17-year-old boy who had features of IAHSP. We also reviewed the current literature on ALS2-related syndromes. METHODS: Clinical and neuroimaging studies were performed. Blood DNA analyses were combined with mRNA studies in cultured skin fibroblasts. RESULTS: Like previously described cases, the patient presented with severe spastic paraparesis and showed rapid progression of paresis to the upper limbs. He also developed bulbar involvement and severe scoliosis during childhood. In blood DNA we identified a novel splice-site homozygous mutation in ALS2 (c.3836+1G > T), producing exon skipping in fibroblast mRNA and predicting premature protein truncation. CONCLUSIONS: This case adds to the allelic heterogeneity of IAHSP. Review of the pertinent literature indicates a fairly homogeneous clinical picture in IAHSP that should facilitate molecular confirmation and prevention of long-term complications.