hereditary spastic paraplegia 5A

Hereditary Spastic Paraplegia 5A (SPG5A) is a rare genetic disorder that affects the nervous system, causing progressive muscle stiffness and weakness in the lower limbs.

Characteristics:

• Pure phenotype: Some patients have a pure form of spastic paraplegia, affecting only their gait, with symptoms such as slowly progressive spasticity and bladder dysfunction [1][2].
• Complex presentation: Others may experience a complex presentation with additional manifestations, including:
  • Cerebellar signs (e.g., ataxia)
  • Nystagmus
  • Distal or generalized muscle atrophy
  • Cognitive impairment [3][4]
• Autosomal recessive inheritance: SPG5A is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Symptoms:

• Progressive muscle stiffness and weakness in the lower limbs
• Bladder dysfunction
• Pes cavus (high arches)
• Cerebellar signs (e.g., ataxia)
• Nystagmus
• Distal or generalized muscle atrophy
• Cognitive impairment

References:

[1] Context 1: Spastic paraplegia type 5A is one of a group of genetic disorders known as hereditary spastic paraplegias.

[2] Context 11: Some patients have pure spastic paraplegia affecting only gait, whereas others may have a complicated phenotype with additional manifestations...

[3] Context 10: Autosomal recessive spastic paraplegia type 5A is a form of hereditary spastic paraplegia characterized by either a pure phenotype or a complex presentation with additional manifestations...

[4] Context 12: Description. Autosomal recessive spastic paraplegia type 5A is a form of hereditary spastic paraplegia characterized by either a pure phenotype or a complex presentation...

Hereditary Spastic Paraplegia (HSP) 5A is a genetic condition that affects the nervous system, leading to progressive weakness and stiffness in the legs. The signs and symptoms of HSP 5A can vary from person to person, but here are some common ones:

• Progressive leg weakness: This is one of the primary symptoms of HSP 5A, where individuals experience a gradual weakening of their leg muscles.
• Muscle stiffness (spasticity): People with HSP 5A often experience muscle stiffness or spasms in their legs, which can be painful and uncomfortable.
• Difficulty walking: As the condition progresses, individuals may find it increasingly difficult to walk or maintain balance due to the weakening of their leg muscles.
• Reduced bladder control: Some people with HSP 5A may experience reduced bladder control or urinary frequency, which can be a source of discomfort and embarrassment.
• High arches of the feet (pes cavus): This is another common symptom of HSP 5A, where individuals develop high arches in their feet due to muscle weakness.

It's essential to note that the age of onset for HSP 5A can vary significantly, ranging from early childhood to adulthood. Additionally, some people may experience other symptoms such as vision impairment, ataxia, epilepsy, cognitive impairment, peripheral neuropathy, and deafness, although these are not as common in HSP 5A.

References:

• [1] Sep 1, 2017 — They may also have muscle wasting (amyotrophy), reduced bladder control, or high arches of the feet (pes cavus). The signs and symptoms of ...
• [5] Sep 1, 2017 — They may also have muscle wasting (amyotrophy), reduced bladder control, or high arches of the feet (pes cavus). The signs and symptoms of ...
• [6] Oct 16, 2024 — Hereditary spastic paraplegia (HSP) symptoms include progressive weakening in the legs, urinary bladder disturbances, spasticity, abnormal gait ...

Hereditary Spastic Paraplegia Type 5A (HSP5A) is a genetic disorder that affects the nervous system, causing progressive muscle weakness and stiffness in the lower limbs. Diagnostic tests for HSP5A are crucial for accurate diagnosis and management of the condition.

Genetic Testing

Genetic testing is a key diagnostic tool for HSP5A. The Invitae Hereditary Spastic Paraplegia Comprehensive Panel analyzes genes associated with hereditary spastic paraplegia (HSP), including the most common genetic causes of HSP, such as SPAST, ATL1, and SPG11 [2]. This panel tests 103 genes, including the most common genetic causes of Hereditary Spastic Paraplegia (HSP) [4].

Other Diagnostic Tests

In addition to genetic testing, other diagnostic tests may be used to rule out other disorders and confirm a diagnosis of HSP5A. These include:

• Neurological exam: A neurological exam is essential for diagnosing HSP5A. The exam assesses muscle strength, reflexes, and coordination [3].
• MRI scans: MRI scans of the brain and spine may be used to rule out other disorders that can cause similar symptoms [6].
• Cerebrospinal fluid analysis: Cerebrospinal fluid analysis may also be performed to rule out other conditions [6].

Multigene Panels

Several multigene panels are available for diagnosing HSP5A, including:

• A 75-gene panel that includes assessment of non-coding variants [7].
• A 128-gene panel that utilizes next-generation sequencing to detect single nucleotide and copy number variants associated with hereditary spastic paraplegia [8].

Clinical Genetic Tests

Clinical genetic tests are also available for diagnosing HSP5A, including:

• Sequence analysis of the entire coding region [10].
• Bi-directional Sanger sequence analysis offered by Duzen Laboratories [10].

It is essential to note that a clinical diagnosis of HSP5A is based on medical and family history, neurological and neuropsychological evaluations, neuropathological studies, other ancillary testing, and exclusion of metabolic disorders [11].

Hereditary Spastic Paraplegia 5A (SPG5A) is a rare neurodegenerative disorder caused by mutations in the CYP7B1 gene. While there are no specific treatments that can cure SPG5A, various pharmacological therapies have been explored to manage its symptoms.

Antispasmodic drugs: Antispasmodic medications may help alleviate spasticity and allow for targeted muscle strengthening through physical therapy. These drugs include botulinum toxin, which has been administered to ambulatory individuals with HSP, including those with SPG5A [1].

Other pharmacological therapies: A study of 17 articles on pharmacological therapy found that various medications have been used to treat SPG5A symptoms, including gabapentin, progabide, dalfampridine, L-Dopa, and cholesterol-lowering drugs [3]. However, the effectiveness of these treatments can vary depending on individual cases.

Emerging therapies: Recent research has focused on potential therapeutic strategies for SPG5A. One such approach involves replacing the CYP7B1 gene through mRNA administration [2]. Additionally, chenodeoxycholic acid has been shown to restore lipid balance and halt axonal degeneration in stem cell-derived SPG5 neurons in laboratory settings [6].

Treatment goals: The primary treatment goal for individuals with SPG5A is to manage symptoms and slow disease progression. This may involve a combination of pharmacological therapies, physical therapy, and other interventions tailored to individual needs.

References: [1] Oct 16, 2024 — Botulinum toxin was administered to ambulatory persons with HSP, with the treatment goals and targeted muscles differing within the group. [2] by S Hauser · 2019 · Cited by 26 — A potential therapeutic strategy for SPG5 is the replacement of CYP7B1 by administration of mRNA. Here, we studied the intravenous application ... [3] by M Bellofatto · 2019 · Cited by 75 — The drugs used in the 17 articles on pharmacological therapy were: gabapentin, progabide, dalfampridine, botulinum toxin, L-Dopa, cholesterol-lowering drugs, ... [6] Jun 4, 2023 — Chenodeoxycholic acid restores lipid balance and stops axonal degeneration in stem cell-derived SPG5 neurons in the lab.

Hereditary Spastic Paraplegia (HSP) 5A, also known as SPG5A, is a rare genetic disorder that affects the nervous system. The differential diagnosis for HSP 5A involves considering various conditions that can present with similar symptoms.

Conditions to Consider:

• Structural abnormalities: Tethered cord syndrome and spinal cord compression are two structural abnormalities that can cause spastic paraplegia.
• Inflammatory, infectious, or metabolic disorders: Conditions such as multiple sclerosis, B12 deficiency, adrenomyeloneuropathy, and other inflammatory, infectious, or metabolic disorders can also present with similar symptoms.
• Other neurodegenerative disorders: HSP 5A should be differentiated from other neurodegenerative disorders such as amyotrophy, mental retardation, parkinsonism, and peripheral neuropathy.

Key Features to Consider:

• Age of onset: The age at which symptoms appear can help narrow down the differential diagnosis. For example, in HSP 5A, symptoms typically appear in adolescence but can begin at any time between infancy and mid-adulthood.
• Clinical features: The presence of additional manifestations such as cerebellar signs, nystagmus, distal or generalized muscle atrophy, bladder dysfunction, and pes cavus can also help differentiate HSP 5A from other conditions.

References:

• [4] Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities.
• [10] Differential Diagnosis of Hereditary Spastic Paraplegia The differential diagnosis includes the following: Structural abnormalities involving the brain or spinal cord (e.g., tethered cord syndrome and spinal cord compression)
• [13] Disease Overview. Autosomal recessive spastic paraplegia type 5A (SPG5A) is a form of hereditary spastic paraplegia characterized by either a pure phenotype of slowly progressive spastic paraplegia of the lower extremities with bladder dysfunction and pes cavus or a complex presentation with additional manifestations including cerebellar signs, nystagmus, distal or generalized muscle atrophy.

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