Spastic paraplegia-54 mainly affects the fibers of the corticospinal tract, and it belongs to a genetically heterogeneous group of neurodegenerative disorders; spastic paraplegias. Patients suffer delayed psychomotor development, mental retardation, and early-onset (by age 2 years) spasticity of the lower limbs. Further neurological manifestations can be identified through brain MRI, such as thinning of corpus callosum and periventricular white matter lesions. Additionally, magnetic resonance spectroscopy of the brain shows an abnormal lipid peak indicating accumulation of lipids. The symptoms of SPG54 are not limited to the central nervous system; head and neck, gastrointestinal and skeletal features are also observed. Examples include; strabismus, dysphagia and foot contractures. These signs and symptoms make the basis for diagnosing SPG54, especially using cerebral magnetic resonance spectroscopy to detect the abnormal lipid peak.
A large consanguineous Omani family was reported by Al-Yahyaee et al. (2006), who identified a number of family members suffering SPG54. In these patients a homozygous mutation in the DDHD2 gene, resulting in premature termination codon (R516X) was published in Schuurs-Hoeijmakers et al. (2012). All the affecteds suffered intellectual disability and/or developmental delay, spastic paraplegia, hyperreflexia and foot contractures. Spasticity in upper limbs and dysphasia were variably noticed. No fecal or urinary incontinence was observed.