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.

CASE REPORT:

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: Annalisa Sechi, Andrea Dardis, Stefania Zampieri, Claudio Rabacchi, Paolo Zanoni, Sebastiano Calandra, Giovanna De Maglio, Stefano Pizzolitto, Valerio Maruotti, Antonio Di Muzio, Frances Platt, Bruno Bembi
• Journal: Orphanet journal of rare diseases (Orphanet J Rare Dis) Vol. 9 Pg. 143 (Sep 18 2014) ISSN: 1750-1172 [Electronic] England
• PMID: 25227739 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• 1-Deoxynojirimycin
• miglustat

Topics

• 1-Deoxynojirimycin (analogs & derivatives, therapeutic use)
• ATP Binding Cassette Transporter 1 (genetics)
• Female
• Humans
• Middle Aged
• Tangier Disease (diagnosis, drug therapy, genetics)
• Treatment Outcome