Case report: A Chinese patient with spinocerebellar ataxia finally confirmed as Gerstmann-Sträussler-Scheinker syndrome with P102L mutation

Abstract

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare genetic prion disease caused by a mutation in the prion protein (PRNP) gene. It is typically characterized by progressive cerebellar ataxia and slowly progressive dementia. We present a case study of the GSS from China in which a 45-year-old male with a progressive gait and balance disorder developed cerebellar ataxia onset but was misdiagnosed as spinocerebellar ataxia (SCA) for 2 years. The patient's clinical, electrophysiological, and radiological data were retrospectively analyzed. Examination revealed ataxia, dysarthria, muscle weakness, areflexia in lower limbs, including a pyramidal sign, whereas cognitive decline was insignificant. His late mother had a similar unsteady gait. An electroencephalogram (EEG) showed normal findings, and 14-3-3 protein was negative. A brain MRI was performed for global brain atrophy and ventricular enlargement. Positron emission tomography-computed tomography (PET-CT) (18F-fluoro-2-deoxy-d-glucose, FDG) images showed mild to moderate decreased glucose metabolism in the left superior parietal lobe and left middle temporal lobe. According to genetic testing, his younger brother also had the P102L variant in the PRNP gene. This single case adds to the clinical and genetic phenotypes of GSS.

Keywords: Gerstmann-Sträussler-Scheinker syndrome; P102L; PRNP gene; prion disease; spinocerebellar ataxia (SCA).

Figure 1

Video electroencephalogram (EEG) showed normal findings.

Figure 2

Magnetic resonance imaging (MRI) of the brain. Axial T2-weighted (A, B) and sagittal T2-weighted scan (C) revealed enlarged sulci in the cerebrum. Fluid-attenuated inversion recovery (FLAIR) sequences (D–F) revealed global brain atrophy, ventricular enlargement.

Figure 3

PET-CT images showed the left superior parietal lobe (A) and left middle temporal lobe (B) had mild to moderate decreased glucose metabolism, with reductions of 10 and 19%, respectively.

Figure 4

(A) Pedigree and PRNP sequences of the proband and his brother. Squares indicate men, circles indicate women, black symbols indicate affected individuals, gray indicates symptoms of presumed GSS, diagonal lines across symbols indicate deceased individuals, and the arrow indicates the proband. for GSS, and for symptoms of presumed GSS. (B) II-1: PRNP sequence of the patient reveals a heterozygous substitution from C to T at position 305 of PRNP cDNA, resulting in an amino acid change from proline to leucine at position 102 (P102L mutation). II-2: PRNP sequence of his little brother confirms the P102L mutation. The arrow indicates the mutation.