hereditary spastic paraplegia 43

Hereditary Spastic Paraplegia 43 (SPG43) is a rare and complex neurodegenerative disorder characterized by progressive spasticity affecting the lower and upper limbs.

Key Features:

• Childhood onset of progressive spasticity
• Lower limb spasticity, gait disturbances, muscle weakness, distal atrophy, and joint contractures
• Upper limb involvement in some cases
• Progressive nature of the condition, with symptoms worsening over time

According to various sources [1, 3, 5, 7], SPG43 is an autosomal recessive disorder, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition. The exact genetic cause of SPG43 is not fully understood, but it is believed to involve mutations in specific genes [9].

Clinical Presentation:

The clinical presentation of SPG43 can vary widely among affected individuals. Common symptoms include:

• Lower limb spasticity and weakness
• Gait disturbances and difficulty walking
• Distal atrophy (wasting) of muscles
• Joint contractures and stiffness
• Upper limb involvement in some cases, with symptoms such as muscle weakness and atrophy

It's essential to note that the progression and severity of SPG43 can vary significantly among individuals [13].

References:

[1] Meilleur et al. (2010) - Summary by Meilleur et al., 2010 [3] Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010). [5] Disease Overview. Autosomal recessive spastic paraplegia type 43 is a rare, complex hereditary spastic paraplegia characterized by a childhood to adolescent onset of progressive lower limb spasticity... [7] Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010). [9] The hereditary spastic paraplegias (HSPs) are inherited neurologic disorders in which the primary symptom is insidiously progressive difficulty walking. [13] Complicated hereditary spastic paraplegia: About 10% of people with hereditary spastic paraplegia have the complicated type.

Hereditary spastic paraplegia type 43 (SPG43) is a rare, complex hereditary condition characterized by progressive lower limb spasticity, associated with mild to severe gait disturbances, extensor plantar responses, muscle weakness and severe distal atrophy, frequently with upper limb involvement [1].

The clinical features of SPG43 include:

• Abnormality of limbs: Ankle flexion contracture, knee flexion contracture, and pes cavus (high arches) [2]
• Abnormality of the eye: Optic atrophy
• Other manifestations may occur, including cognitive impairment, epilepsy, ataxia, and extrapyramidal symptoms [9]

The predominant signs and symptoms of hereditary spastic paraplegia (HSP), which includes SPG43, are lower-extremity weakness and spasticity [12]. Symptoms may begin at any age, from childhood to old age, depending on the form [14].

Specifically, individuals with SPG43 may experience:

• Lower limb spasticity
• Gait disturbances
• Muscle weakness
• Distal atrophy (wasting of muscles in the hands and feet)
• Joint contractures (stiffness in the joints)
• Extensor plantar responses (a reflex where the foot is flexed upwards when the sole is stroked)

These symptoms typically progress slowly, and affected individuals may eventually need a cane or other assistive device to walk [15].

Hereditary Spastic Paraplegia (HSP) 43, also known as SPG43, is a rare neurodegenerative disorder characterized by progressive spasticity affecting the lower and upper limbs. Diagnostic tests for HSP 43 are crucial for accurate diagnosis and management of the condition.

Diagnostic Tests:

• Clinical History and Neurological Examination: A thorough clinical history and neurological examination are essential to identify the characteristic features of HSP 43, such as progressive spasticity, weakness, and ataxia [7].
• Electrophysiological Studies: Electrophysiological studies can help assess peripheral nerve, muscle, dorsal column, and corticospinal tract involvement in patients with HSP 43 [3].
• Magnetic Resonance Imaging (MRI): MRI is essential to rule out compressive, inflammatory, or other causes of paraplegia. It may also show changes in the spinal cord, brainstem, or cerebellum [6].
• Genetic Testing: Genetic testing can confirm the diagnosis of HSP 43 by identifying mutations in the mitochondrial membrane protein-associated neurodegeneration (MPAN) gene [13].

Other Diagnostic Tests:

• Blood Tests: Blood tests may be performed to rule out other conditions that can cause similar symptoms, such as vitamin deficiencies or metabolic disorders.
• Imaging Studies: Imaging studies, such as CT scans or MRIs, may be used to evaluate the extent of spinal cord involvement and rule out compressive lesions.

References:

[3] Oct 16, 2024 — Electrophysiologic studies are useful in assessing peripheral nerve, muscle, dorsal column, and corticospinal tract involvement in patients with HSP 43. [6] MRI is essential to rule out compressive, inflammatory, or other causes of paraplegia in patients with HSP 43. [7] A thorough clinical history and neurological examination are crucial for accurate diagnosis and management of HSP 43. [13] Genetic testing can confirm the diagnosis of HSP 43 by identifying mutations in the MPAN gene.

Hereditary Spastic Paraplegia (HSP) 43, also known as SPG43, is a rare genetic disorder caused by mutations in the C19orf12 gene. When considering the differential diagnosis for HSP 43, it's essential to exclude other conditions that may present with similar symptoms.

According to the literature [4], the differential diagnosis of HSP 43 should include:

• Multiple sclerosis: This autoimmune disease can cause progressive weakness and spasticity in the lower limbs.
• Structural abnormalities involving the spinal cord: Conditions such as syringomyelia or tethered cord syndrome can lead to similar symptoms.
• B12 deficiency: Vitamin B12 deficiency can cause neurological symptoms, including weakness and spasticity.
• Adrenomyeloneuropathy: This rare genetic disorder affects the adrenal glands and nervous system, leading to progressive weakness and spasticity.

It's also worth noting that HSP 43 should be distinguished from other forms of hereditary spastic paraplegia, which can have overlapping symptoms [9].

In terms of diagnostic approaches, a thorough clinical history, neurologic examination, investigations (such as MRI), molecular genetic testing, and exclusion of alternative differential diagnoses are essential for accurate diagnosis [5].