Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism.

Abstract

BACKGROUND:

Autosomal recessive hereditary spastic paraplegia with thin corpus callosum is a neurodegenerative disorder characterized by spastic paraparesis, cognitive impairment, and peripheral neuropathy. The neuroradiologic hallmarks are thin corpus callosum and periventricular white matter changes. Mutations in the SPG11 gene have been identified to be a major cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and recently also proven to be responsible for juvenile parkinsonism associated with spastic paraplegia.

METHODS:

We describe one Italian autosomal recessive hereditary spastic paraplegia with thin corpus callosum patient who unusually presented at onset, 16 years, with parkinsonism-like features, responsive to dopaminergic therapy. Then the clinical picture evolved and became more complex. A brain magnetic resonance imaging scan showed thin corpus callosum and hyperintense T(2)-weighted lesions in periventricular regions, and the (123)I-ioflupane single-photon emission coupled tomography was abnormal.

RESULTS:

Genetic analysis detected two novel mutations, a c.3664insT variant in compound heterozygosity with a c.6331insG mutation, in SPG11.

DISCUSSION:

This case confirms the high genetic and clinical heterogeneity associated with SPG11 mutations. It also offers further evidence that parkinsonism may initiate autosomal recessive hereditary spastic paraplegia with thin corpus callosum and that parkinsonian symptoms can have variable dopaminergic response in these patients.

• Authors: Arianna Guidubaldi, Carla Piano, Filippo M Santorelli, Gabriella Silvestri, Martina Petracca, Alessandra Tessa, Anna Rita Bentivoglio
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 26 Issue 3 Pg. 553-6 (Feb 15 2011) ISSN: 1531-8257 [Electronic] United States
• PMID: 21381113 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Movement Disorder Society.

Chemical References

• Antiparkinson Agents
• Proteins
• SPG11 protein, human
• Levodopa

Topics

• Adult
• Antiparkinson Agents (therapeutic use)
• Female
• Genome-Wide Association Study (methods)
• Humans
• Levodopa (therapeutic use)
• Magnetic Resonance Imaging (methods)
• Mutation (genetics)
• Parkinson Disease (complications, drug therapy, genetics)
• Proteins (genetics)
• Spastic Paraplegia, Hereditary (etiology, genetics)