SPG11 spastic paraplegia

Autosomal recessive hereditary spastic paraplegia (AR HSP) with thin corpus callosum (TCC) is a rare neurodegenerative disorder often caused by mutations in the gene encoding for spatacsin at the SPG11 locus on chromosome 15q. The disease is characterized by progressive spastic paraparesis and mental retardation which occur during the first two decades of life and frequently with peripheral neuropathy. Brain magnetic resonance imaging (MRI) reveals typical TCC with periventricular white matter changes. We describe two patients, of Turkish descent, from the same consanguineous family and affected with SPG11 in association with unusual early-onset parkinsonism. Parkinsonism occurred during the very early stages of SPG11 in both patients, being in one the inaugural symptom of the disease presented as a resting tremor with akinesia, rigidity and expressing an initial moderate levodopa-response that progressively weakened. The second patient presented a resting tremor with mild akinesia and no levodopa-response. Both patients were affected with progressive spastic paraparesis which had initially occurred at 15 and 12 years of age, respectively, in association with mild mental retardation and an axonal polyneuropathy. TCC with periventricular white matter changes (PWMC) was evident by MRI and ¹²³I-ioflupane SPECT was abnormal. Genetic analysis detected for both patients a new c.704_705delAT, p.H235RfsX12 homozygous mutation in SPG11. This report provides evidence that parkinsonism may initiate SPG11-linked HSP TCC and that SPG11 may cause juvenile parkinsonism.