Spastic paraplegia 3

Alternate names

SPG3A; SPG3; Strumpell disease

Definition

A rare, pure or complex subtype of hereditary spastic paraplegia, with highly variable phenotype, typically characterized by childhood-onset of minimally progressive, bilateral, mainly symmetric lower limb spasticity and weakness, associated with pes cavus, diminished vibration sense, sphincter disturbances and/or urinary bladder hyperactivity. Additional associated manifestations may include scoliosis, mild intellectual disability, optic atrophy, axonal motor neuropathy and/or distal amyotrophy.

Cause

Mutations in the ATL1 gene cause spastic paraplegia type 3A.<ref>Hedera P. Spastic Paraplegia 3A. 2010 Sep 21 [Updated 2020 Jun 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK45978/ </ref>[1].

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Spastic paraplegia type 3A is inherited in an autosomal dominant pattern.

Signs and symptoms

Spastic paraplegia 3A (SPG3A; also known as ATL1-HSP) is characterized by slowly progressive bilateral and mostly symmetric spasticity and weakness of the legs, and with a variable degree of diminished vibration sense (caused by degeneration of the corticospinal tracts and dorsal columns) and urinary bladder hyperactivity.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Babinski sign
• Distal lower limb muscle weakness
• Lower limb hyperreflexia(Overactive lower leg reflex)
• Lower limb spasticity

30%-79% of people have these symptoms

• Ankle clonus(Abnormal rhythmic movements of ankle)
• Distal lower limb amyotrophy
• Spastic gait(Spastic walk)

5%-29% of people have these symptoms

• Hypoplasia of the corpus callosum(Underdevelopment of part of brain called corpus callosum)
• Impaired vibratory sensation(Decreased vibration sense)
• Intellectual disability, mild(Mental retardation, borderline-mild)
• Motor delay
• Toe walking(Toe-walking)
• Urinary urgency(Overactive bladder)

1%-4% of people have these symptoms

• Bradykinesia(Slow movements)
• Dysarthria(Difficulty articulating speech)
• Frequent falls
• Growth delay(Delayed growth)
• Hyperesthesia
• Lower limb hypertonia
• Rigidity(Muscle rigidity)

Diagnosis

The diagnosis of ATL1-HSP is established in a proband with suggestive findings and almost exclusively a heterozygous pathogenic variant in ATL1 identified by molecular genetic testing.<ref>Hedera P. Spastic Paraplegia 3A. 2010 Sep 21 [Updated 2020 Jun 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK45978/ </ref>[2].

Treatment

• Treatment is symptomatic.
• Medical treatment of spasticity may begin with oral baclofen or tizanidine, followed by chemodenervation with botulinum A or B toxins if oral antispasticity medications are not tolerated.
• Intrathecal baclofen pump may be considered for those who improve on oral baclofen but have significant systemic adverse effects.
• Medical therapy should be combined with intensive physical therapy focused on stretching and strengthening exercises that may help delay or minimize muscle tendon contractures, scoliosis, and foot deformities.
• Distal weakness (typically affecting foot dorsiflexion) can be ameliorated by ankle-foot orthoses.
• Urinary urgency can be treated with anticholinergic antispasmodic drugs.<ref>Hedera P. Spastic Paraplegia 3A. 2010 Sep 21 [Updated 2020 Jun 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK45978/

</ref>[3].

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NIH genetic and rare disease info

• NIH info on Spastic paraplegia 3

Spastic paraplegia 3 is a rare disease.