Late-onset spastic paraplegia type 10 (SPG10)

Posted - May 2016 in Research Highlights

First-time discovered in an Asian family

 

Japanese researchers have for the first time found SPG10 HSP in an Asian family. Age of onset was 60 years. One other family member also has this form of HSP, with 4 other family members also carrying the genetic mutation but showing no symptoms.

 

Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features.

 

We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS).

 

Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles.

 

This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS.

 

SOURCE: J Neurol Sci. 2016 May 15;364:45-9. doi: 10.1016/j.jns.2016.03.001. Epub 2016 Mar 2. Copyright © 2016 Elsevier B.V. All rights reserved. PMID: 27084214 [PubMed – in process]

 

Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis.

 

Kaji S1, Kawarai T2, Miyamoto R3, Nodera H4, Pedace L5, Orlacchio A6, Izumi Y7, Takahashi R8, Kaji R9.

 

1 Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan; Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: [email protected]

2 Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: [email protected]

3 Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: [email protected]

4 Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: [email protected]

5 Laboratorio di Neurogenetica, CERC-IRCCS Santa Lucia, Rome, Italy. Electronic address: [email protected]

6 Laboratorio di Neurogenetica, CERC-IRCCS Santa Lucia, Rome, Italy; Dipartimento di Scienze Chirurgiche e Biomolecolari, Università di Perugia, Perugia, Italy. Electronic address: [email protected]

7 Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: [email protected]

8 Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: [email protected]

9 Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan. Electronic address: [email protected]

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