Abstract
BACKGROUND: Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort. METHODS: We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015. RESULTS: Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6 months or (1b) before the age of 5 years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects. CONCLUSIONS: Overall long-term (>5 years) survival of subjects with two disease-causing ABCA3 mutations was
Original language | English |
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Pages (from-to) | 213-220 |
Number of pages | 8 |
Journal | Thorax |
Volume | 72 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 1 2017 |
Keywords
- ATP-Binding Cassette Transporters/genetics
- Adolescent
- Adult
- Biopsy
- Bronchoalveolar Lavage Fluid/chemistry
- Child
- Child, Preschool
- Consanguinity
- Diagnostic Imaging
- Female
- Genotype
- Humans
- Immunohistochemistry
- Infant
- Infant, Newborn
- Lung Diseases, Interstitial/genetics/mortality
- Male
- Microscopy, Electron
- Mutation
- Phenotype
- Retrospective Studies
- Survival Analysis
- ABCA3
- Paediatric interstitial lung disease
- Surfactant protein