SPG30 is an autosomal recessive form of slowly progressive spastic paraplegia characterized by onset in the first or second decades of unsteady spastic gait and hyperreflexia of the lower limbs. Mildly impaired sensation and cerebellar involvement has been ... SPG30 is an autosomal recessive form of slowly progressive spastic paraplegia characterized by onset in the first or second decades of unsteady spastic gait and hyperreflexia of the lower limbs. Mildly impaired sensation and cerebellar involvement has been reported in 1 putatively affected family (summary by Erlich et al., 2011).
Klebe et al. (2006) reported a consanguineous family of Algerian origin in which 4 sibs had hereditary spastic paraplegia. Mean age at onset of stiff legs and unsteady spastic gait was 17.5 years (range 12 to 21). Other ... Klebe et al. (2006) reported a consanguineous family of Algerian origin in which 4 sibs had hereditary spastic paraplegia. Mean age at onset of stiff legs and unsteady spastic gait was 17.5 years (range 12 to 21). Other clinical features included hyperreflexia of the lower limbs and extensor plantar responses. Two sibs had distal sensory loss, primarily pinprick sensation, and 2 had saccadic ocular movements. Three sibs had subtle cerebellar signs, including ataxia, and subsequent brain imaging of 1 of them showed mild diffuse cerebellar atrophy. Disease progression was slow; all patients remained ambulatory for up to 15 years after disease onset. Klebe et al. (2006) concluded that the disorder in this family was a form of complicated SPG with cerebellar involvement and peripheral neuropathy. Klebe et al. (2012) provided follow-up of the family reported by Klebe et al. (2006). The disorder showed slow progression and all patients were able still able to walk after disease duration of 9 to 22 years, although maximal walking distance was reduced. Erlich et al. (2011) reported 3 Palestinian sibs with early childhood onset of slowly progressive spastic paraplegia. They were examined at ages 20, 15, and 14 years, respectively. Although they could participate in sports in childhood, symptoms became more severe between ages 10 and 13 years, and the patients could no longer play, run, or walk long distances. Physical examination showed scissoring gait, lower limb spasticity, hyperreflexia, and extensor plantar responses, most severe in the oldest patient. None had weakness, distal sensory loss, or cognitive dysfunction. Klebe et al. (2012) reported a consanguineous Palestinian family with genetically confirmed SPG30. Age at onset was available for 3 patients only, and occurred at ages 10, 11, and 39 years. All patients had spasticity with hyperreflexia and extensor plantar responses. Most had distal muscle wasting and weakness as well as impaired pinprick and vibration sense. Two patients tested had an axonal sensorimotor peripheral neuropathy, and brain imaging of these 2 patients was normal. None had saccadic ocular pursuit or sphincter disturbances.
By homozygosity mapping, exome sequencing, and examination of candidate genes, Erlich et al. (2011) identified a homozygous mutation in the KIF1A gene (A255V; 601255.0001) in 3 Palestinian sibs with pure hereditary spastic paraplegia.
Klebe et al. ... By homozygosity mapping, exome sequencing, and examination of candidate genes, Erlich et al. (2011) identified a homozygous mutation in the KIF1A gene (A255V; 601255.0001) in 3 Palestinian sibs with pure hereditary spastic paraplegia. Klebe et al. (2012) identified a homozygous mutation in the KIF1A gene (R350G; 601255.0005) in affected members of a consanguineous Algerian family with SPG30 originally reported by Klebe et al. (2006). Another Palestinian family with the disorder was found to be homozygous for the A255V mutation.