ASAH1 variant causing a mild SMA phenotype with no myoclonic epilepsy: a clinical, biochemical and molecular study

Massimiliano Filosto, Massimo Aureli, Barbara Castellotti, Fabrizio Rinaldi, Domitilla Schiumarini, Manuela Valsecchi, Susanna Lualdi, Raffaella Mazzotti, Viviana Pensato, Silvia Rota, Cinzia Gellera, Mirella Filocamo, Alessandro Padovani

Research output: Contribution to journalArticlepeer-review


ASAH1 gene encodes for acid ceramidase that is involved in the degradation of ceramide into sphingosine and free fatty acids within lysosomes. ASAH1 variants cause both the severe and early-onset Farber disease and rare cases of spinal muscular atrophy (SMA) with progressive myoclonic epilepsy (SMA-PME), phenotypically characterized by childhood onset of proximal muscle weakness and atrophy due to spinal motor neuron degeneration followed by occurrence of severe and intractable myoclonic seizures and death in the teenage years. We studied two subjects, a 30-year-old pregnant woman and her 17-year-old sister, affected with a very slowly progressive non-5q SMA since childhood. No history of seizures or myoclonus has been reported and EEG was unremarkable. The molecular study of ASAH1 gene showed the presence of the homozygote nucleotide variation c.124A>G (r.124a>g) that causes the amino acid substitution p.Thr42Ala. Biochemical evaluation of cultured fibroblasts showed both reduction in ceramidase activity and accumulation of ceramide compared with the normal control. This study describes for the first time the association between ASAH1 variants and an adult SMA phenotype with no myoclonic epilepsy nor death in early age, thus expanding the phenotypic spectrum of ASAH1-related SMA. ASAH1 molecular analysis should be considered in the diagnostic testing of non-5q adult SMA patients.European Journal of Human Genetics advance online publication, 30 March 2016; doi:10.1038/ejhg.2016.28.

Original languageEnglish
JournalEuropean Journal of Human Genetics
Publication statusAccepted/In press - Mar 30 2016

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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