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Autosomal Recessive Spastic Paraplegia Type 44

Autosomal Recessive Spastic Paraplegia 44


Presentation

  • Phenotypic homogeneity of the Huntington disease-like presentation in a SCA17 family. Neurology 2006;67(9):1701-3. Schneider SA, Walker RH, Bhatia KP.[books.google.com]
  • HSP is classified according to the clinical phenotype as either pure or complex, the latter presenting with neurological and systemic impairments in addition to spastic paraparesis.[journals.lww.com]
  • Nystagmus, truncal ataxia and incordination of movements were present. Fundus examination showed bilateral optic atrophy.[ijmr.org.in]
  • Muscle weakness when present is seen in iliopsoas, tibialis anterior and, to a lesser extent, the hamstrings.[jnnp.bmj.com]
  • Asymptomatic patients are also present.[emedicine.medscape.com]
Movement Disorder
  • She has always had a great interest in movement disorders with focus on movement disorder genetics and electrophysiology. She holds a Ph.D. degree in neurosciences from University College London.[books.google.com]
  • Movement Disord 2016; 31: S227-S.[hih-tuebingen.de]
  • Movement Disorders 32: 332–345. Tallaksen CM, Dürr A and Brice A (2001) Recent advances in hereditary spastic paraplegia. Current Opinion in Neurology 14: 457–463.[els.net]
  • […] mutations are frequent in young-onset autosomal dominant spastic paraplegia Arch Neurol, 61 (12), 1867-72 DOI 10.1001/archneur.61.12.1867, PubMed 15596607 Tallaksen CM, Dietrichs E (2004) [The genetics of movement disorders--spinocerebellar degenerations[ous-research.no]
  • Movement Disorders. 2008;23(2):228-33. de Niet M, de Bot ST, van de Warrenburg BP, Weerdesteyn V, Geurts AC.[en.wikipedia.org]
Respiratory Insufficiency
  • However, patients with PPS commonly develop new disabilities that cause significant morbidity, such as orthopedic complications (eg, progressive instability of joints, osteoporosis, fractures, osteoarthrosis, scoliosis, and spondylosis), respiratory insufficiency[emedicine.medscape.com]
Vascular Disease
  • Thus, a careful medical history and clinical examination are necessary to exclude all other conditions that may cause similar symptoms, which include ALS, multiple sclerosis, collagen vascular diseases, depression, hypothyroidism, myasthenia gravis, inclusion[emedicine.medscape.com]
Suggestibility
  • Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. Hum Mol Genet. PubMed PMID: 24973356 Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer's disease. N Engl J Med.[books.google.com]
  • […] below. 9 Further subdivision of pure HSP was also suggested by Harding based on the age of onset of the disease.[jnnp.bmj.com]
  • Normal results of muscle histochemical and biochemical analysis suggest that mitochondrial disturbance, a feature of chromosome 16-linked autosomal recessive HSP due to paraplegin gene mutations, is not a feature of chromosome 8q-linked autosomal dominant[neurology.org]
  • They are stained light red by methyl green-pyronin, which suggests that they have an RNA component.[emedicine.medscape.com]
  • Nevertheless, in all our patients, there was a relationship between the location and severity of white matter changes and the atrophy of the corpus callosum, suggestive of an atrophic process of the corpus callosum.[ajnr.org]
Dystonia
  • She has received many awards, among others the European Dystonia Society David Marsden Award and the AAN Jon Stolk Award in Movement Disorders for Young Investigators.[books.google.com]
  • Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM: 612718 ] GBA2 Q9HCG7 non-pleiotropic Spastic paraplegia 46, autosomal recessive (SPG46) [MIM: 614409 ] GCDH Q92947 non-pleiotropic Glutaric aciduria 1 (GA1) [MIM: 231670 ] GCH1 P30793 pleiotropic Dystonia[sbg.bio.ic.ac.uk]
  • Edvardson S, Hama H, Shaag A, et al. (2008) Mutations in the fatty acid 2‐hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. American Journal of Human Genetics 83: 643–648.[els.net]
  • […] frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases J Med Genet, 43 (3), 259-65 DOI 10.1136/jmg.2005.035311, PubMed 16055926 Dietrichs E, Tallaksen CM (2004) [Genetics in movement disorders--dystonia[ous-research.no]
  • Fink JK, Filling-Katz M, Barton NW, et al.: Treatable dystonia presenting as spastic cerebral palsy . Pediatrics 1988, 82 :138. Google Scholar 70.[link.springer.com]
Hyperreflexia
  • People with this condition can also experience exaggerated reflexes (hyperreflexia), ankle spasms, high-arched feet (pes cavus), and reduced bladder control.[ghr.nlm.nih.gov]
  • The gait is spastic with weakness, hyperreflexia, and extensor plantar responses in the lower limbs. The upper limbs are variably involved and movements are dysmetric. Dysarthria and bladder dysfunction are often present.[disorders.eyes.arizona.edu]
  • Examination at the age of 22 years after a traffic accident revealed failure of abduction of the left eye, hyperreflexia in all four extremities and Babinski sign.[journals.plos.org]
  • Diagnosis of SPG is established by the following clinical features 1, 2 : Typical clinical symptoms of spastic gait impairment and neurologic findings of spastic weakness, hyperreflexia, typically associated with bilateral extensor plantar responses A[centogene.com]
  • Upper limb involvement is relatively uncommon and usually consists of mild hyperreflexia, which may be present early in the disease. A trace of terminal dysmetria may also be found in the upper limbs, but more florid cerebellar signs are not seen.[jnnp.bmj.com]
Spastic Gait
  • If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years.[ipfs.io]
  • Diagnosis of SPG is established by the following clinical features 1, 2 : Typical clinical symptoms of spastic gait impairment and neurologic findings of spastic weakness, hyperreflexia, typically associated with bilateral extensor plantar responses A[centogene.com]
  • Keywords Hereditary Spastic Paraplegia Spastic Paraparesis Primary Lateral Sclerosis Spastic Gait Hereditary Spastic Paraparesis These keywords were added by machine and not by the authors.[link.springer.com]
  • Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus collasum in spastic gait gene 11 (SPG11). Arch Neurol 2004 ; 61 : 117 –21 Ohnishi J, Tomoda Y, Yokoyama K.[ajnr.org]
Lower Extremity Spasticity
  • extremity spasticity and weakness.[flybase.org]
  • All forms of HSP, complicated and uncomplicated, share the primary symptom of lower-extremity spastic weakness.[invitae.com]
  • The following individuals are candidates for spastic paraplegia-related gene testing: Individuals with a family history of hereditary spastic paraplegia and presentation of lower extremity spasticity and weakness and other common symptoms Individuals[centogene.com]
  • Given that both of these disorders are treatable, dopa-responsive dystonia should be excluded in a child with progressive gait disturbance and lower-extremity spasticity of unknown etiology, whereas arginase deficiency should be considered in a young[emedicine.medscape.com]
Dysmetria
  • Cerebellar signs were present in 4 patients (family I) and consisted of a dysarthric cerebellar speech, dysmetria, and abnormal rapid alternating movements in the upper extremities.[ajnr.org]
  • A trace of terminal dysmetria may also be found in the upper limbs, but more florid cerebellar signs are not seen.[jnnp.bmj.com]
  • Moderate truncal ataxia was present with bilateral dysmetria and dysdiadochokinesia. It was not possible to assess cerebellar function in the legs due to weakness.[journals.plos.org]

Workup

  • Our findings confirm that this is indeed not an uncommon presentation of this disorder and we suggest that SPG7 gene analysis should be included in the diagnostic workup of autosomal recessive PEO, especially if spasticity is present.[journals.plos.org]

Treatment

  • Treatment Treatment Options: No effective treatment is known for the neurological deficits but cataract surgery may be beneficial for visually significant cataracts.[disorders.eyes.arizona.edu]
  • Treatment [ edit ] No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being.[en.wikipedia.org]
  • It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.[uniprot.org]
  • Marelli C, Lamari F, Rainteau D, et al. (2018) Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5. Brain 141: 72–84.[els.net]
  • The majority of individuals with HSP have a normal life expectancy. [2] Treatment No specific treatment is known that would prevent, slow, or reverse HSP.[ipfs.io]

Prognosis

  • Abstract Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited.[nature.com]
  • Prognosis Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals.[ipfs.io]
  • Prognosis [ edit ] Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals.[en.wikipedia.org]
  • This distinction is important for genetic counseling of family members and for the patient’s prognosis, in that HSP generally carries a more favorable prognosis. [2] Other components of the differential diagnosis of HSP are similar to those of PLS.[emedicine.medscape.com]
  • Disorders, the prognosis of which differs significantly from HSP, such as multiple sclerosis and familial motor neuron disease should also be excluded. The necessity for investigations will vary depending on the individual clinical picture.[jnnp.bmj.com]

Etiology

  • Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. Hum Mol Genet. PubMed PMID: 24973356 Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer's disease. N Engl J Med.[books.google.com]
  • Accordingly, plasma oxysterols are biomarkers that should be included in the screening of any spastic paraplegia of unknown etiology.[oxfordmedicine.com]
  • Primary lateral sclerosis The etiology of primary lateral sclerosis (PLS) is unknown, but it may be similar to that proposed for ALS.[emedicine.medscape.com]
  • Keppen L, Leppert M, O'Connell P (1987) Etiological heterogeneity in X-linked spastic paraplegia. Am J Hum Genet 41:933-43. Kobayashi H, Hoffman EP, Marks HG (1994) The rumpshaker mutation in spastic paraplegia. Nature Genet 7:351-2.[med.umich.edu]
  • Etiological heterogeneity in X-linked spastic paraplegia. Am J Hum Genet 1987 ; 41 : 933 –43 Goldblatt J, Ballo R, Sachs B, et al. X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype.[ajnr.org]

Epidemiology

  • Consequently, they are often approached together in epidemiological studies.[karger.com]
  • The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014; 42(3):174-83.[invitae.com]
  • Epidemiology Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. [15] A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000[ipfs.io]
  • , Durmus H, Brenner T, Vaknin A, Berrih-Aknin S, Frenkian Cuvelier M, Stojkovic T, DeBaets M, Losen M, Martinez-Martinez P, Kleopa KA, Zamba-Papanicolaou E, Kyriakides T, Kostera-Pruszczyk A, Szczudlik P et al. (2013) A comprehensive analysis of the epidemiology[ous-research.no]
  • Epidemiology The prevalence of HSP varies in different studies. Such variation is probably due to a combination of differing diagnostic criteria, variable epidemiological methodology, and geographical factors.[jnnp.bmj.com]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology [ edit ] The major feature of HSP is a length dependent axonal degeneration. [21] These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis.[en.wikipedia.org]
  • Koenig[ 10 ] proposed a classification of ARCA based on topographical and pathophysiological criteria, while in the next year the group of Filla proposed a pathogenic classification of the hereditary ataxias[ 11 ].[wjgnet.com]

Prevention

  • The majority of individuals with HSP have a normal life expectancy. [2] Treatment No specific treatment is known that would prevent, slow, or reverse HSP.[ipfs.io]
  • Treatment [ edit ] No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being.[en.wikipedia.org]
  • Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology.[karger.com]
  • Bjorkhem, Sulphatation does not appear to be a protective mechanism to prevent oxysterol accumulation in humans and mice. PLoS One, 2013. 8(7): p. e68031. Martin, E.*, R. Schule*, K. Smets*, A. Rastetter, A. Boukhris, J.L. Loureiro, M.A.[hih-tuebingen.de]

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