SPG26 is an autosomal recessive form of complicated spastic paraplegia characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional ... SPG26 is an autosomal recessive form of complicated spastic paraplegia characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional features include intellectual disability, peripheral neuropathy, dysarthria, cerebellar signs, extrapyramidal signs, and cortical atrophy. The disorder is slowly progressive (summary by Boukhris et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Farag et al. (1994) reported a consanguineous Kuwaiti family in which 5 sibs had complicated spastic paraplegia. At age 8 years, the proband developed progressive dysarthria and walking difficulties with high step and frequent falls. Clinical examination at ... Farag et al. (1994) reported a consanguineous Kuwaiti family in which 5 sibs had complicated spastic paraplegia. At age 8 years, the proband developed progressive dysarthria and walking difficulties with high step and frequent falls. Clinical examination at age 13 years showed spastic paraparesis, scissor gait, toe walking, brisk reflexes, extensor plantar responses and pes cavus, and wasting of the small muscles of the hands and feet. Cerebellar function, EEG, and nerve conduction velocities were all normal. The clinical phenotype was similar in all affected sibs. Wilkinson et al. (2005) reported that mild intellectual impairment was present in some affected individuals. Boukhris et al. (2013) reported 5 families in which several family members had autosomal recessive spastic paraplegia. The families were from various countries of origin, including Spain, Tunisia, Brazil, Portugal, and Germany. Several of the families were consanguineous. Patients had onset in the first or second decades (range, 2 to 19 years) of gait abnormalities due to lower limb spasticity, hyperreflexia, extensor plantar responses, muscle weakness and atrophy, and mild to moderate intellectual disability. About a third of patients also had mild upper limb involvement. Other features were more variable, including decreased vibration sense at the ankles, pseudobulbar dysarthria, pes cavus, scoliosis, urinary symptoms, dyskinesia, dystonia, cataracts, and cerebellar signs. Four males had decreased testosterone, and 1 female had early menopause. EMG in many patients showed an axonal sensorimotor neuropathy, and brain MRI showed cortical atrophy and white matter hyperintensities. Two additional patients were later identified from a cohort of 65 index cases. The severity was variable; 4 patients became wheelchair-bound or bedridden after many years. Hyporeflexia became apparent later in the disease course.
By exome sequencing of 5 families with autosomal recessive SPG, Boukhris et al. (2013) identified 5 different homozygous mutations in the B4GALNT1 gene. The mutations segregated with the disorder in the family and were not found in large ... By exome sequencing of 5 families with autosomal recessive SPG, Boukhris et al. (2013) identified 5 different homozygous mutations in the B4GALNT1 gene. The mutations segregated with the disorder in the family and were not found in large control databases. Subsequent analysis of this gene identified mutations in 2 of 65 additional probands with a similar disorder. All mutations were truncating, except for 2 missense mutations that occurred at highly conserved residues (see, e.g., 601873.0001-601873.0005). No functional studies were performed.