sábado, 13 de mayo de 2017

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients | Orphanet Journal of Rare Diseases | Full Text

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients | Orphanet Journal of Rare Diseases | Full Text

Biomed Central

Orphanet Journal of Rare Diseases

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

  • Elena Maria PennisiEmail authorView ORCID ID profile,
  • Marcello Arca,
  • Enrico Bertini,
  • Claudio Bruno,
  • Denise Cassandrini,
  • Adele D’amico,
  • Matteo Garibaldi,
  • Francesca Gragnani,
  • Lorenzo Maggi,
  • Roberto Massa,
  • Sara Missaglia,
  • Lucia Morandi,
  • Olimpia Musumeci,
  • Elena Pegoraro,
  • Emanuele Rastelli,
  • Filippo Maria Santorelli,
  • Elisabetta Tasca,
  • Daniela Tavian,
  • Antonio Toscano,
  • Corrado Angelini and
  • The Italian NLSD Group
Orphanet Journal of Rare Diseases201712:90
DOI: 10.1186/s13023-017-0646-9
Received: 12 October 2016
Accepted: 3 May 2017
Published: 12 May 2017

Abstract

Background

A small number of patients affected by Neutral Lipid Storage Diseases (NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been described in various ethnic groups worldwide. However, relatively little is known about the progression and phenotypic variability of the disease in large specific populations. The aim of our study was to assess the natural history, disability and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one patients who satisfied the criteria for NLSDs were enrolled in a retrospective cross-sectional study to evaluate the genetic aspects, clinical signs at onset, disability progression and comorbidities associated with this group of diseases.

Results

During the clinical follow-up (range: 2–44 years, median: 17.8 years), two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five (24%) lost their ability to walk or needed help when walking after a mean period of 30.6 years of disease. None of the patients required mechanical ventilation. No patient required a heart transplant, one patient with NLSD-M was implanted with a cardioverter defibrillator for severe arrhythmias.

Conclusion

The genotype/phenotype correlation analysis in our population showed that the same gene mutations were associated with a varying clinical onset and course. This study highlights peculiar aspects of Italian NLSD patients that differ from those observed in Japanese patients, who were found to be affected by a marked hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same mutations, it is conceivable that some additional genetic or epigenetic factors affect the symptoms and progression in this group of diseases.

Keywords

NLSD PNPLA2 CGI58 Myopathy Lipid metabolism Natural history

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