Symptoma

Autosomal Recessive Spastic Paraplegia Type 48

SPG48

Most patients presented with spastic paraparesis. Additional features included ataxia, dystonia, intellectual impairment, myoclonus, and parkinsonism. One patient presented with pure sensory and motor neuropathy. [ng.neurology.org]

Autosomal recessive HSP as well as sporadic cases present a significant diagnostic challenge. [mobile.fluidigm.com]

Abstract Objective: To identify the gene mutation responsible for a family presenting spastic paraplegia, cerebellar ataxia and neuropathy with autosomal recessive transmission. [trace.ddbj.nig.ac.jp]

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]

CASE PRESENTATION: We describe a Chinese family with ARHSP-TCC. Two daughters of this family presented with a spastic gait and cognitive impairment. Brain imaging of the index patient revealed a thin corpus callosum. [hspersunite.org.au]

  • Pallor

    The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. [genecards.org]

    Discs show mild temporal pallor. An EMG/NCS indicated an axonal sensory polyneuropathy. Somatosensory evoked potentials showed an abnormal central response in the right upper limb. [ng.neurology.org]

    There is diffuse myelin pallor of crossed and uncrossed corticospinal tracts. In addition, the gracile fasciculi in the centre of the dorsal columns show prominent myelin pallor. Anterior horn cells are normal in number and morphology. [jnnp.bmj.com]

  • Numbness of the Feet

    He developed a spastic bladder and pain and numbness in both feet. On examination, the patient exhibited prominent lower extremity spasticity with mild distal muscle weakness and mild weakness of the hip flexors. Cognition was intact. [ng.neurology.org]

  • Hypomimia

    As his gait problems progressed, his family noted facial hypomimia and bradykinesia. He developed a spastic bladder and pain and numbness in both feet. [ng.neurology.org]

  • 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]

    Two daughters of this family presented with a spastic gait and cognitive impairment. Brain imaging of the index patient revealed a thin corpus callosum. [hspersunite.org.au]

    Winner B, Uyanik G, Gross C et al. (2004) Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11). Archives of Neurology 61: 117–121. [els.net]

  • Shuffling Gait

    The patient presented for evaluation after he developed a stiff, shuffling gait at age 60, leading to frequent tripping and occasional falls. This gradually progressed to the point where he needed a walker to ambulate. [ng.neurology.org]

    gait and adducted thumbs) syndrome, spastic paraplegia 1) neural cell adhesion molecule L1 L1CAM CAML1 CD171 HSAS HSAS1 MASA MIC5 S10 SPG1 308840 6470 lysine demethylase 5C DXS1272E XE169 KDM5C JARID1C MRX13 SMCX 314690 11114 lysosomal trafficking regulator [ukgtn.nhs.uk]

    Different mutations in this gene give rise to the syndromes of MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs), X-linked hydrocephalus, and X-linked agenesis of the corpus callosum. [jnnp.bmj.com]

  • Bradykinesia

    As his gait problems progressed, his family noted facial hypomimia and bradykinesia. He developed a spastic bladder and pain and numbness in both feet. [ng.neurology.org]

    Charcots studies between 1868 and 1881 were a landmark in the understanding of Parkinsons disease, among other advances he made the distinction between rigidity, weakness and bradykinesia. [wikivisually.com]

    Only one of five patients with hereditary spastic paraplegia showed clinical indication of extrapyramidal involvement in the form of subtle bradykinesia and slight resting tremor. [intechopen.com]

  • Lower Extremity Spasticity

    On examination, the patient exhibited prominent lower extremity spasticity with mild distal muscle weakness and mild weakness of the hip flexors. Cognition was intact. [ng.neurology.org]

    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]

  • Neurologic Manifestation

    Kosofsky, Weill-Cornell University Medical Center - Neurologic Manifestations of Medical Disorders-John C. Probasco, Johns Hopkins University [books.google.com]

She developed urinary incontinence, and urological workup disclosed a spastic bladder. No dementia was evident. [ng.neurology.org]

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]

  • White Matter Lesions

    In family I, the white matter lesions were more prominent in older patients ( Fig 1 A ), in contrast to family III, where the white matter lesions were more prominent in the younger patients. [ajnr.org]

    MRI of the brain disclosed white matter lesions affecting the basal ganglia and deep white matter and focal atrophy of the corpus callosum ( figure 1 ), while a full spine MRI was normal. [ng.neurology.org]

    There are occasional reports of mild to moderate atrophy of intracranial structures, particularly the corpus callosum, and also of white matter lesions in the cerebral hemispheres. 15 71 79 80 However, marked atrophy or changes in white matter on MRI [jnnp.bmj.com]

The second edition of Neurobiology of Disease includes nearly 200 articles surveying all major disorders of the nervous system in both adults and children, focusing on relevant diagnosis and treatments from the perspective of cutting edge clinical and [books.google.com]

The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. ‎ [books.google.it]

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]

Lancet Neurol 9:885–894 CrossRef PubMed Google Scholar Ehlert K, Frosch M, Fehse N et al (2007) Farber disease: clinical presentation, pathogenesis and a new approach to treatment. [link.springer.com]

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]

Identification of the specific mutation concerned is essential to establishing a prognosis and providing satisfactory treatment and proper genetic counselling. [elsevier.es]

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]

Accordingly, plasma oxysterols are biomarkers that should be included in the screening of any spastic paraplegia of unknown etiology. [oxfordmedicine.com]

Risch N et al. (1999) A genomic screen of autism: evidence for a multilocus etiology. [ ] 26. [moldiag.com]

The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. [genecards.org]

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]

MtDNA defects of either primary or secondary etiology are known to segregate predominantly in clinically affected tissues. [journals.plos.org]

Consequently, they are often approached together in epidemiological studies. [karger.com]

Relevant External Links for SPG11 Genetic Association Database (GAD) SPG11 Human Genome Epidemiology (HuGE) Navigator SPG11 Atlas of Genetics and Cytogenetics in Oncology and Haematology: SPG11 No data available for Genatlas for SPG11 Gene Mutations in [genecards.org]

Jorde LB et al. (1990) The UCLA-University of Utah epidemiologic survey of autism: genealogical analysis of familial aggregation. [ ] 6. Abramson RK et al. (1989) Elevated blood serotonin in autistic probands and their first-degree relatives. [ ] 7. [moldiag.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]

Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management. [elsevier.es]

See Hereditary Peripheral Neuropathies Testing Algorithm in Special Instructions Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Inherited peripheral neuropathies are a relatively [mayomedicallaboratories.com]

Conclusions: Our findings expand the spectrum of AP5Z1 -associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. [ng.neurology.org]

J Clin Endocrinol Metab 93:2084–2088 CrossRef PubMed Google Scholar Werner ER, Blau N, Thöny B (2011) Tetrahydrobiopterin: biochemistry and pathophysiology (review). [link.springer.com]

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]

Pathophysiological insights into ALS with C9ORF72 expansions. Journal of Neurology, Neurosurgery and Psychiatry, 84(8), 931-935. [sydney.edu.au]

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]

Extra genetic material from the X chromosome interferes with male sexual development, preventing the testicles from functioning normally, males with Klinefelter syndrome typically have one extra copy of the X chromosome in each cell, for a total of two [wikivisually.com]

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]