eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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SCImago Journal & Country Rank
3/2019
vol. 57
 
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abstract:
Case report

Clinical and ultrastructural findings in an ataxic variant of Kufor-Rakeb syndrome

Anna Pietrzak
,
Magdalena Badura-Stronka
,
Tiia Kangas-Kontio
,
Paulina Felczak
,
Wojciech Kozubski
,
Anna Latos-Bielenska
,
Teresa Wierzba-Bobrowicz
,
Jolanta Florczak-Wyspianska

Folia Neuropathol 2019; 57 (3): 285-294
Online publish date: 2019/09/30
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Introduction
Kufor-Rakeb syndrome (KRS) is a rare autosomal recessive neurodegenerative disorder manifesting as juvenile-onset atypical parkinsonism with pyramidal signs, supranuclear gaze palsy, dementia and characteristic minimyoclonus, with a notable phenotype variability. The responsible gene ATP13A2 was also associated with hereditary spastic paraplegia, uncomplicated early – or late-onset parkinsonism and a form of neuronal ceroid lipofuscinosis. We present clinical and ultrastructural findings in a 28-year-old woman with novel biallelic ATP13A2 mutations.

Material and methods
An ultrastructural study of the skin and muscle sample was carried out. Sequence analysis of all protein coding exons and exon-intron boundaries of genes was performed on patient’s genomic DNA. A proprietary oligonucleotide-selective sequencing method was used for capturing genomic targets and sequencing was performed using Illumina sequencing system.

Results
The patient presented with juvenile-onset progressive parkinsonian syndrome and cognitive deterioration, accompanied by mild spastic paraplegia, supranuclear gaze palsy, cerebellar syndrome, peripheral neuropathy and fine myoclonus. Plentiful and varied osmiophilic deposits were found in skin and muscle biopsy. Sequence analysis identified two novel heterozygous variants in ATP13A2: a nonsense variant c.2209C>T, p.(Gln737*) and a 2-bp deletion c.2366_2367delTC, p.(Leu789Argfs*15) causing a frameshift leading to a premature stop codon. Oral levodopa treatment was initiated resulting in marked improvement of bradykinesia, rigidity, speech and swallowing.

Conclusions
We report two novel ATP13A2 pathogenic mutations, further expanding the phenotype of Kufor-Rakeb syndrome with the unusual features of ataxia and polyneuropathy. We thoroughly describe ultrastructural findings and document a meaningful response to levodopa.

keywords:

ATP13A2, PARK9, Kufor-Rakeb syndrome, Parkinson’s disease, ataxia

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