Triple A syndrome presenting as complicated hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is a group of rare disorders characterized by spastic paraparesis and other symptoms. Often, other diseases can mimic HSP, which may delay diagnosis and treatment.

Whole exome sequencing was performed in families with clinically suspected HSP without a genetic diagnosis.

We report three patients from two families who presented with lower limb spasticity, muscular atrophy, and other neurological symptoms, who were clinically diagnosed with complicated HSP. Whole exome sequencing revealed bi-allelic AAAS nonsense mutations; one individual was homozygous for the p.(Arg478*) mutation, and two siblings were homozygous for the p.(Arg286*) mutation, leading to the diagnosis of triple A syndrome. This rare syndrome is typically characterized by a triad of symptoms: achalasia, adrenal insufficiency, and alacrima, and is often accompanied by other neurological abnormalities.

Our findings suggest that triple A syndrome should be suspected in complicated HSP patients without a known genetic cause, especially if at least one of the main triad of triple A syndrome symptoms is present.