Extremely severe complicated spastic paraplegia 3A with neonatal onset

Spastic paraplegia 3A typically manifests in childhood as an uncomplicated form of hereditary spastic paraplegia with slow progression. Most affected individuals present with spasticity and weakness in the legs before the end of the first decade.

We describe a 12-year-old boy with neonatal onset of extremely severe complicated spastic paraplegia 3A associated with a de novo c.1226G>A (p.G409D) mutation in ATL1, a gene which encodes atlatsin GTPase 1. He manifested general hypertonia and hypokinesia since the neonatal period and was initially diagnosed with cerebral palsy. He was never able to move without assistance because of severe spastic quadriplegia with distal dominant muscle weakness. He also developed with pseudobulbar palsy; his speech, chewing, and swallowing were severely impaired. Electrophysiological studies revealed severe diffuse axonal neuropathy.

Extremely severe complicated spastic paraplegia 3A can be caused by mutations in the linker or three-helix bundle of atlastin 1.