Autosomal recessive spastic paraplegia type 5A

Autosomal recessive spastic paraplegia type 5A (SPG5A), also known as spastic paraplegia 5A, is a rare hereditary spastic paraplegia caused by mutations in the CYP7B1 gene, which encodes an enzyme involved in bile acid and neurosteroid metabolism. The disease primarily affects the nervous system, specifically the upper motor neurons of the corticospinal tract, leading to progressive weakness and spasticity (stiffness) of the lower limbs. SPG5A can present as either a pure or complicated form of hereditary spastic paraplegia. In the pure form, the hallmark features include progressive spasticity and weakness of the legs, hyperreflexia (overactive reflexes), and extensor plantar responses (Babinski sign), with gradual difficulty walking that may eventually require assistive devices. In complicated forms, additional neurological features may be present, including white matter abnormalities on brain MRI, optic atrophy, cerebellar ataxia, and neuropathy. Some patients may also develop urinary urgency or incontinence. The age of onset is variable, ranging from early childhood to adulthood, though many cases present in childhood or adolescence. There is currently no cure or disease-modifying therapy for SPG5A. Treatment is symptomatic and supportive, focusing on physical therapy to maintain mobility and reduce spasticity, antispasticity medications such as baclofen or tizanidine, and management of urinary symptoms. Orthopedic interventions may be considered in some cases. Research into the role of oxysterol accumulation due to CYP7B1 deficiency has raised interest in potential therapeutic strategies targeting bile acid metabolism, but these remain investigational.

Common questions about Autosomal recessive spastic paraplegia type 5A