Autosomal recessive spastic paraplegia type 35

Autosomal recessive spastic paraplegia type 35 (SPG35), also known as fatty acid hydroxylase-associated neurodegeneration (FAHN disease), is a rare hereditary neurodegenerative disorder caused by mutations in the FA2H gene, which encodes fatty acid 2-hydroxylase. This enzyme is essential for the production of 2-hydroxylated sphingolipids, which are critical components of myelin in the central nervous system. SPG35 falls within the broader category of neurodegeneration with brain iron accumulation (NBIA) disorders, as iron deposition in the basal ganglia is frequently observed on brain MRI. The disease primarily affects the nervous system and typically presents in childhood with progressive spastic paraplegia — stiffness and weakness of the lower limbs that worsens over time. As the condition progresses, patients often develop dystonia (involuntary muscle contractions), dysarthria (difficulty with speech), cognitive decline, seizures, cerebellar ataxia, and optic atrophy. White matter abnormalities and thinning of the corpus callosum are commonly seen on neuroimaging. Many affected individuals eventually lose the ability to walk independently and may develop quadriplegia. There is currently no cure or disease-modifying treatment for SPG35. Management is supportive and symptomatic, focusing on physical therapy to maintain mobility, antispasticity medications (such as baclofen or tizanidine), antiepileptic drugs for seizure control, and speech therapy. Orthopedic interventions may be needed for contractures. A multidisciplinary approach involving neurologists, rehabilitation specialists, and other healthcare providers is essential for optimizing quality of life.

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