The clinical course of interstitial lung disease in an adult patient with an ABCA3 homozygous complex allele under hydroxychloroquine and a review of the literature ABCA3 mutations and hydroxychloroquine

Main Article Content

Marie Legendre
Xavier Darde
Marion Ferreira
Sandra Chantot-Bastaraud
Marion Campana
Laurent Plantier
Nadia Nathan
Serge Amselem
Annick Toutain
Patrice Diot
Sylvain Marchand-Adam

Keywords

ILD, ABCA3, hydroxychloroquine

Abstract

The gene mutations responsible for ABCA3 protein deficiency are involved in respiratory distress of the newborn and much more rarely in adult interstitial lung diseases (ILD). An adult patient homozygous for a complex allele encompassing the p.Ala1027Pro likely pathogenic mutation and the p.Gly974Asp variation was followed for a late-onset and fibrotic ILD. The evolution was marked by progressive clinical and functional degradation despite corticosteroid pulses. The patient, who was first registered on the list for lung transplantation, was improved quickly and persistently for at least 6.5 years with hydroxychloroquine treatment, allowing removal from the transplant list.

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References

1 Ban N, Matsumura Y, Sakai H, et al. ABCA3 as a lipid transporter in pulmonary surfactant biogenesis. J Biol Chem. 2007 Mar;282(13):9628–34.
2 Epaud R, Feldmann D, Guillot L, Clément A. [Lung diseases associated with inherited disorders of surfactant metabolism]. Arch Pediatr. 2008 Oct;15(10):1560–7.
3 Williamson M, Wallis C. Ten-year follow up of hydroxychloroquine treatment for ABCA3 deficiency. Pediatr Pulmonol. 2014 Mar;49(3):299–301.
4 Manali ED, Legendre M, Nathan N, et al. Bi-allelic missense ABCA3 mutations in a patient with childhood ILD who reached adulthood. ERJ Open Res. 2019 Jul;5(3):00066–2019.
5 Weichert N, Kaltenborn E, Hector A, et al. Some ABCA3 mutations elevate ER stress and initiate apoptosis of lung epithelial cells. Respir Res. 2011 Jan;12:4.
6 Schindlbeck U, Wittmann T, Höppner S, et al. ABCA3 missense mutations causing surfactant dysfunction disorders have distinct cellular phenotypes. Hum Mutat. 2018 Jun;39(6):841–50.
7 Flamein F, Riffault L, Muselet-Charlier C, et al. Molecular and cellular characteristics of ABCA3 mutations associated with diffuse parenchymal lung diseases in children. Hum Mol Genet. 2012 Feb;21(4):765–75.
8 Epaud R, Delestrain C, Louha M, Simon S, Fanen P, Tazi A. Combined pulmonary fibrosis and emphysema syndrome associated with ABCA3 mutations. Eur Respir J. 2014 Feb;43(2):638–41.
9 Campo I, Zorzetto M, Mariani F, et al. A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant. Respir Res. 2014 Apr;15:43.
10 Klay D, Platenburg MGJP, van Rijswijk RHNAJ, Grutters JC, van Moorsel CHM. ABCA3 mutations in adult pulmonary fibrosis patients: a case series and review of literature. Curr Opin Pulm Med. 2020 May;26(3):293–301.
11 Tomer Y, Wambach J, Knudsen L, et al. The common ABCA3E292V variant disrupts AT2 cell quality control and increases susceptibility to lung injury and aberrant remodeling. Am J Physiol Lung Cell Mol Physiol. 2021 Aug;321(2):L291–307.
12 Kröner C, Wittmann T, Reu S, et al. Lung disease caused by ABCA3 mutations. Thorax. 2017 Mar;72(3):213–20.
13 Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004 Nov;306(5698):990–5.
14 Richard SA, Kampo S, Hechavarria ME, et al. Elucidating the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Chloroquine and Hydroxychloroquine. J Immunol Res. 2020;2020:4582612.
15 Cho J-G, Thakkar D, Buchanan P, Graf N, Wheatley J. ABCA3 deficiency from birth to adulthood presenting as paediatric interstitial lung disease. Respirol Case Rep. 2020 Oct;8(7):e00633.
16 Bullard JE, Wert SE, Whitsett JA, Dean M, Nogee LM. ABCA3 mutations associated with pediatric interstitial lung disease. Am J Respir Crit Care Med. 2005 Oct;172(8):1026–31.