Spastic Paraplegia 5A

Clinical Characteristics
Ocular Features: 

Gaze-evoked nystagmus and saccadic pursuit movements are present in about 10% of patients.  Optic atrophy was reported in one individual.  Rare patients have been reported to have cataracts.  

Systemic Features: 

This is a progressive disorder of neurological deterioration.  Age of onset (mean 16.4 years) and rate of neurological dysfunction are highly variable.  Gait difficulties are the most common presenting signs.  Some gait ataxia is usually present.  The lower limbs are more severely affected by spasticity and weakness and walking is often delayed with difficulty running and clumsiness in childhood.  Some patients (38%) are wheelchair-bound after disease duration of more than 33 years.  Dysphagia and dysarthria are uncommon. 

Some sensory impairments such as impaired vibratory sense, decreased proprioception, and absent touch sensation in the lower extremities are frequently present.  Urge incontinence of bladder and rectum is sometimes a feature.

Genetics

Bialllelic mutations in the CYP7B1 gene (8q12.3) have been identified in this disorder resulting in a marked accumulation of neurotoxic oxysterols in plasma and CSF.

Treatment
Treatment Options: 

No effective treatment for the general disorder has been reported.

References
Article Title: 

Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial

Schols L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jagle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Hoflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Zuchner S, Bassi MT, Klopstock T, De Jonghe P, Bjorkhem I, Schule R. Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain. 2017 Dec 1;140(12):3112-3127.

PubMed ID: 
29126212

CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5

Goizet C, Boukhris A, Durr A, Beetz C, Truchetto J, Tesson C, Tsaousidou M, Forlani S, Guyant-Marechal L, Fontaine B, Guimaraes J, Isidor B, Chazouilleres O, Wendum D, Grid D, Chevy F, Chinnery PF, Coutinho P, Azulay JP, Feki I, Mochel F, Wolf C, Mhiri C, Crosby A, Brice A, Stevanin G. CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain. 2009 Jun;132(Pt 6):1589-600.

PubMed ID: 
19439420

References

Schols L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jagle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Hoflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Zuchner S, Bassi MT, Klopstock T, De Jonghe P, Bjorkhem I, Schule R. Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain. 2017 Dec 1;140(12):3112-3127.

PubMedID: 29126212

Goizet C, Boukhris A, Durr A, Beetz C, Truchetto J, Tesson C, Tsaousidou M, Forlani S, Guyant-Marechal L, Fontaine B, Guimaraes J, Isidor B, Chazouilleres O, Wendum D, Grid D, Chevy F, Chinnery PF, Coutinho P, Azulay JP, Feki I, Mochel F, Wolf C, Mhiri C, Crosby A, Brice A, Stevanin G. CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain. 2009 Jun;132(Pt 6):1589-600.

PubMedID: 19439420

Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH. Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. Am J Hum Genet. 2008 Feb;82(2):510-5.

PubMedID: 18252231