title: Effects of miglustat treatment in a patient affected by an atypical form of Tangier disease.
abstract: BACKGROUND
  Tangier disease (TD) is a rare autosomal recessive disorder, resulting from mutations in the ATP binding cassette transporter (ABCA1) gene. The deficiency of ABCA1 protein impairs high density lipoprotein (HDL) synthesis and cholesterol esters trafficking.
  
  
  METHODS
  A 58 year-old female, presenting with complex clinical signs (splenomegaly, dysarthria, dysphagia, ataxia, tongue enlargement, prurigo nodularis, legs lymphedema, pancytopenia and bone marrow foam cells), was misdiagnosed as Niemann-Pick C (NPC) and treated with miglustat (300 mg/day), normalizing neurological symptoms and improving skin lesions and legs lymphedema. Subsequently filipin-staining and molecular analysis for NPC genes were negative. Lipid profiling showed severe deficiency of HDL, 2 mg/dl (n.v. 45-65) and apoAI, 5.19 mg/dl (n.v. 110-170), suggesting TD as a probable diagnosis. Molecular analysis of ABCA1 gene showed the presence of a novel homozygous deletion (c.4464-486_4698 + 382 Del). Miglustat treatment was then interrupted with worsening of some neurological signs (memory defects, slowing of thought processes) and skin lesions. Treatment was restarted after 7 months with neurological normalization and improvement of skin involvement.
  
  
  CONCLUSIONS
  These results suggest miglustat as a possible therapeutic approach in this untreatable disease. The mechanisms by which miglustat ameliorates at least some clinical manifestations of TD needs to be further investigated.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Sechi
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.forename: Stefania
authors.initials: S
authors.lastname: Zampieri
authors.forename: Claudio
authors.initials: C
authors.lastname: Rabacchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Zanoni
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Maglio
authors.forename: Stefano
authors.initials: S
authors.lastname: Pizzolitto
authors.forename: Valerio
authors.initials: V
authors.lastname: Maruotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Muzio
authors.forename: Frances
authors.initials: F
authors.lastname: Platt
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D013631:Tangier Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D017485:1-Deoxynojirimycin; C059896:miglustat