Spastic Paraplegia 54, Autosomal Recessive

Alternative Names

  • SPG54
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WHO-ICD-10 version:2010

Diseases of the nervous system

Systemic atrophies primarily affecting the central nervous system

OMIM Number


Mode of Inheritance

Autosomal Recessive

Gene Map Locus



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.   

Molecular Genetics

SPG54 is caused by homozygous or compound heterozygous mutations in the DDHD domain-containing protein 2 gene (DDHD2), which is located on chromosome 8. The latter gene is thought to play an essential role in the human CNS, and specifically in synaptic functioning. All identified mutations affect the enzyme’s DDHD domain, which is essential for its phospholipase activity, thus supporting the gene’s role in lipid metabolism.     

Epidemiology in the Arab World

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Other Reports


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.  

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