Fatal respiratory disease due to a homozygous intronic ABCA3 mutation: a case report

Abstract

BackgroundPulmonary surfactant is a complex mixture of lipids and proteins. Mutations in surfactant protein-C, surfactant protein-D, and adenosine triphosphate-binding cassette subfamily A member 3 have been related to surfactant dysfunction and neonatal respiratory failure in full-term babies. Adenosine triphosphate-binding cassette subfamily A member 3 facilitates the transfer of lipids to lamellar bodies. We report the case of patient with a homozygous intronic ABCA3 mutation.Case presentationWe describe a newborn full-term Colombian baby boy who was the son of non-consanguineous parents of mixed race ancestry (Mestizo), who was delivered with severe respiratory depression. Invasive treatment was unsuccessful and diagnosis was uncertain. Exons 4 and 5 of the SP-C gene showed heterozygous Thr138Asn polymorphism and homozygous Asn186Asn polymorphism respectively. At intron 25 at position –98 from exon 26 a homozygous C>T transition mutation was detected in ABCA3 gene.ConclusionsThe clinical presentation and the histopathological findings of this case are consistent with a case of neonatal respiratory failure due to surfactant deficiency. Analysis of the five coding SP-C exons does not support surfactant deficiency. An analysis of the mutation IVS25-98 T was performed and a homozygous mutation responsible for our case’s neonatal respiratory failure was detected. The findings suggest an autosomic recessive pattern of inheritance. Genetic counseling was provided and the relatives are now informed of the recurrence risks and treatment options.

Hydroxychloroquine, a successful treatment for lung disease in ABCA3 deficiency gene mutation: a case report

“…Clinically, surfactant dysfunction disorders present usually with moderate to severe respiratory distress and signs of diffuse lung disease without satisfactory history or laboratory findings [13].…”

Fatal Respiratory Failure in a Term Newborn Due to Non-previously Described Compound Heterozygous ABCA3 Mutations

“…[1][2][3][4] ABCA3 protein is codified by a single gene with 33 exons located on the short arm of chromosome 16. [3][4][5][6][7][8] The clinical spectrum and severity of lung disease caused by ABCA3 mutations vary from fatal surfactant deficiency in full-term newborn infants to later-onset chronic interstitial lung disease in older children. More than 400 mutations in ABCA3 have been reported to date, 9 many of them leading to severe neonatal disease presentation.…”