Variants in ASAH1 are known to be associated with two disease entities, namely: (1) Farber lipogranulomatosis, a rare disease characterized by subcutaneous, periarticular nodules, painful contractures, a hoarse voice, central nervous system involvement, and sometimes hepatosplenomegaly (OMIM #228000), and: (2) spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA-PME), a childhood-onset, progressive lower motor neuron degeneration with refractory, myoclonic epilepsy (OMIM #159950). Other features may include hearing loss, tremor, or cognitive dysfunction. Thus far, around 25 individuals with SMA-PME have been reported—though not all cases were confirmed by genotyping and/or documentation of deficient acid ceramidase activity. [1,2,3,4,5,6,7,8,9] Recently, Filosto et al. [10] described two siblings with an SMA phenotype, but without myoclonic epilepsy due to variants in ASAH1, further expanding the phenotypical spectrum. We now report a third, unrelated, case with ASAH1 related SMA.

A now 24-year-old female with no other relevant past medical history first sought care for slowly progressive muscle weakness and muscle cramps in the arms and legs at the age of 19 years. She was born to non-consanguineous parents, and early developmental motor milestones had been achieved at appropriate ages. Her first ambulatory problems—walking more slowly—arose at the age of eight years. She had been an active dancer during her childhood, but experienced problems crouching and maintaining some positions from age 14 on and had to stop practicing at the age of 15. From this age onward, she increasingly experienced problems with climbing stairs (by now systematically using the banister), raising herself from the floor, and carrying heavy loads above shoulder height. At her most recent visit to our hospital (at 23 years of age), she was still able to walk about two kilometers, but had near-falls 2–3 times a year. Additionally, she complained of mild exercise dyspnea. She did not have any sleep disturbances, or swallowing difficulties. She had never experienced seizures or myoclonic jerks. On examination, she had atrophy and fasciculations of the tongue, postural tremor of the hands (improved by beta-blockers), bilateral scapular winging, axial weakness (neck flexion MRC grade 4), bilateral proximal weakness of the arms (shoulder anteflexion MRC grade 3, shoulder abduction/elbow flexion/elbow extension MRC grade 4) and legs (hip flexors MRC grade 3, knee flexors MRC grade 4), and also a slight distal weakness of the hands. Sensory investigations were normal.

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