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Publications

Journal Article Review Ahead of print

PubMed: 41919582 DOI: 10.1002/mdc3.70613

Niemann Pick Type C Presenting as Familial Late-Onset Richardson Syndrome. A Case Series of Four Siblings.

Mov Disord Clin Pract

Authors: Vasilios C Constantinides, Christos Koros, Andreas Kyrozis, Eftychia Papathanasiou, Christos Manginas, Georgios Armenis, Faidra Kalligerou, Argyro Daskalaki, Chrysoula Koniari, Nikolaos Ragazos, Zoi Kontogeorgiou, Chrisoula Kartanou, Emmanouela Linardaki, Nektarios Tavernarakis, Georgia Karadima, Georgios Koutsis, Elisabeth Kapaki, Nikolaos Scarmeas, Leonidas Stefanis, Sokratis G Papageorgiou

Affiliations

  • First Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Neurochemistry and Biological Markers Unit, First Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Neurogenetics Unit, First Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Greece.
  • Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece.

Abstract

BACKGROUND

Niemann Pick Type C (NP-C) is a rare lysosomal disorder, characterized by clinical heterogeneity. Late age of onset (> 40 years) is exceedingly rare, with approximately 20 reports to date. Herein, we describe four siblings with disease onset over 40 years of age.

CASES

Two of the siblings fulfilled criteria for probable PSP with Richardson syndrome (PSP-RS), whereas the remaining cases had atypical clinical features, with prominent cerebellar symptoms and overt frontal-executive dysfunction, fulfilling criteria for probable PSP-RS and probable PSP with predominant frontal presentation (PSP-F). All patients reported hearing loss. DaT-scans were normal in two of the cases, and midbrain atrophy was absent. EEG was abnormal, with generalized paroxysms and short sequences of delta slow waves in one of the cases. All patients had a homozygous point mutation c.2861C>T, p.(Ser954Leu) in the NPC1 gene.

LITERATURE REVIEW

A literature review supported the association between the c.2861C>T, p.(Ser954Leu) mutation in the NPC-1 gene and late-onset NP-C. Cerebellar signs, early-onset hearing loss, normal DaT-scan and absence of midbrain atrophy in brain MRI are red flags for a PSP diagnosis and should prompt further investigations for alternative diagnoses, including NP-C.

CONCLUSIONS

Late onset (>40 years) NP-C, particularly due to c.2861C>T, p.(Ser954Leu) mutation in the NPC-1 gene, can mimic Richardson syndrome.

MeSH

Genes, Supranuclear Palsy, Progressive, Atrophy, Brain, Hearing, Mesencephalon, Signs And Symptoms, Niemann-Pick Diseases, Siblings, Diagnosis, Hearing Loss, Mutation