Hereditary spastic paraparesis

BACKGROUND: Hereditary spastic paraparesis (HSP) is a group of rare genetic disorders affecting the central nervous system. Pure HSP is limited to lower limb spasticity and urinary voiding dysfunction. Complex HSP involves additional neurological features. Beyond the described core symptoms, knowledge about the burden of disease for adults with HSP is limited, particularly regarding gastrointestinal functions, fecal incontinence, and urinary symptoms. METHODS: We conducted a cross-sectional self-report survey with 108 adult HSP patients (Mage  = 57...

We collected the gait parameters and lower limb joint kinematics of patients with three different types of primary degenerative neurological diseases: (i) cerebellar ataxia (19 patients), (ii) hereditary spastic paraparesis (26 patients), and (iii) Parkinson's disease (32 patients). Sixty-five gender-age matched healthy subjects were enrolled as control group. An optoelectronic motion analysis system was used to measure time-distance parameters and lower limb joint kinematics during gait in both patients and healthy controls...

BACKGROUND: Toe walking (TW) in children is often idiopathic in origin. Our purpose was to determine the incidence of a neurological etiology for TW in patients seen in the neurology clinic after referral from pediatric orthopaedic surgeons. METHODS: We performed an Institutional Review Board approved retrospective review of 174 patients referred to the neurology clinic from orthopaedic surgeons at an academic pediatric tertiary care center between January 2010 and September 2015...

BACKGROUND AND PURPOSE: Juvenile- or adult-onset forms of severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting as complicated hereditary spastic paraplegia have rarely been described. METHODS: Two siblings with mental retardation developed a progressive spastic paraparesis in their late teens. Their diagnostic assessment included extensive neurophysiologic, neuroimaging and metabolic studies. RESULTS: Brain magnetic resonance imaging showed occipital white matter alterations, and electromyography documented a mixed polyneuropathy...

We present a Finnish family in which adrenomyeloneuropathy (AMN) caused by the mutation in the ABCD1 gene was revealed as the cause of spastic paraparesis. . Two patients had hypoadrenalism, which is in some cases some associated with the disease . AMN is a hereditary disease manifested both in men and women. but owing to the location of the gene in the X chromosome the symptoms are usually more severe in male patients. . Diagnoses was trucked down with gene-panel sequencing and confirmed through detection of an elevated level of very long-chain fatty acids in the serum of the patients...

OBJECTIVES: Cooling of the lower limb in people with Hereditary and Spontaneous Spastic Paraparesis (pwHSSP) has been shown to affect walking speed and neuromuscular impairments. The investigation of practical strategies, which may help to alleviate these problems is important. The potential of superficial heat to improve walking speed has not been explored in pwHSSP. Primary objective was to explore whether the application of superficial heat (hot packs) to lower limbs in pwHSSP improves walking speed...

Autosomal recessive hereditary spastic paraparesis is rare.We present 4 patients with slowly progressive predominantly lower limb spasticity and ataxia. Only one patient had family history of ataxia but without any underlying diagnosis. All of them proved negative for the mutation of Spinocerebelalr ataxia genes SCA 1,2,3 and 6. All had mutation in the SPG 7 gene suggestive of autosomal recessive hereditary spastic paraparesis. One of the heterozygous mutatnts showed a novel c1617delC ,p(Val540fs) frameshift mutation in exon 12 of the SPG 7 gene...

No abstract text is available yet for this article.

AIM OF THE STUDY: To investigate the mutation frequency of SPG11, SPG15, SPG5 and SPG7 in China. MATERIALS AND METHODS: We have scanned the whole exons of KIAA1840, ZFYVE26, SPG7 and CYP7B1 genes in a group of 36 unrelated Chinese ARHSP families. RESULTS: SPG11 mutations were found in 33.33% (12/36) of ARHSP patients in our study, and no mutation was identified in SPG15, SPG5 or SPG7 genes. Among the SPG11 mutations detected, c.1755_1758delAGCA/p...

Reported is a case of a man aged 55 years who presented with progressive spastic paraparesis. Examination demonstrated multiple cutaneous telangiectases. Subsequent development of upper limb weakness, acute urinary retention and eventual respiratory compromise resulted in the requirement for intensive care unit admission and mechanical ventilation. MRI spine revealed diffuse T2 hyperintensity in the cervical cord with enhancement and cord expansion. Immunomodulatory therapy for a presumed diagnosis of transverse myelitis yielded no response, so a vascular aetiology was suspected...

Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders characterized by progressive spasticity of the lower limbs due to degeneration of the corticospinal motor neurons. In a Bulgarian family with three siblings affected by complicated hereditary spastic paraplegia, we performed whole exome sequencing and homozygosity mapping and identified a homozygous p.Thr512Ile (c.1535C > T) mutation in ATP13A2. Molecular defects in this gene have been causally associated with Kufor-Rakeb syndrome (#606693), an autosomal recessive form of juvenile-onset parkinsonism, and neuronal ceroid lipofuscinosis (#606693), a neurodegenerative disorder characterized by the intracellular accumulation of autofluorescent lipopigments...

Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine...

Hereditary spastic paraplegias (HSPs) are a group of heterogeneous neurodegenerative disorders, which are often presented with overlapping phenotypes such as progressive paraparesis and spasticity. To assist the diagnosis of HSP subtypes, next-generation sequencing is often used to provide supporting evidence. In this study, we report the case of two probands from the same family with HSP symptoms, including bilateral lower limb weakness, unsteady gait, cognitive decline, dysarthria, and slurring of speech since the age of 14...

BACKGROUND: Spastic gait is a key feature in patients with hereditary spastic paraparesis, but the gait characterization and the relationship between the gait impairment and clinical characteristics have not been investigated. OBJECTIVES: To describe the gait patterns in hereditary spastic paraparesis and to identify subgroups of patients according to specific kinematic features of walking. METHODS: We evaluated fifty patients by computerized gait analysis and compared them to healthy participants...

Hereditary spastic paraplegias (HSPs; SPG1-76 plus others) are length-dependent disorders affecting long corticospinal axons, and the most common autosomal dominant forms are caused by mutations in genes that encode the spastin (SPG4), atlastin-1 (SPG3A) and REEP1 (SPG31) proteins. These proteins bind one another and shape the tubular endoplasmic reticulum (ER) network throughout cells. They also are involved in lipid droplet formation, enlargement, or both in cells, though mechanisms remain unclear. Here we have identified evidence of partial lipoatrophy in Reep1 null mice in addition to prominent spastic paraparesis...

No abstract text is available yet for this article.

OBJECTIVE: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype-phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. METHODS: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. RESULTS: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein...

The Guillain-Barré syndrome (GBS) is one of the few neuropathies well known to the general public, in part because of its association with swine flu vaccinations in 1976. GBS has again reached the general public with its possible association with Zika virus. The virus, borne by infected Aedes aegypti mosquitos, is being linked to birth defects when pregnant women are bitten and infected. There are early reports also linking GBS to Zika infection, which could expose a wider range of infected people to the neuropathy...

Troyer syndrome is an autosomal recessive form of hereditary spastic paraplegia (HSP) caused by deleterious mutations in the SPG20 gene. Although the disease is associated with a loss of function mechanism of spartin, the protein encoded by SPG20, the precise pathogenesis is yet to be elucidated. Recent data indicated an important role for spartin in both mitochondrial maintenance and function. Here we report a child presenting with progressive spastic paraparesis, generalized muscle weakness, dysarthria, impaired growth, and severe isolated decrease in muscle cytochrome c oxidase (COX) activity...

BACKGROUND AND PURPOSE: The term hereditary spastic paraplegia (HSP) covers a spectrum of genetically heterogeneous disorders in which lower limb spasticity is the common clinical feature. Many patients with childhood-onset HSP are mistakenly diagnosed with cerebral palsy (CP). METHODS: A group of as yet molecularly undiagnosed HSP patients were analyzed using SpastoPlex, a customized target re-sequencing panel able to investigate the coding regions of 72 genes linked to HSP, spastic ataxias or related motor diseases...