RESUMEN
Mutations in the gene for adenosine triphosphate-binding cassette transporter A3 (ABCA3) have been reported in infants and children with fatal surfactant deficiency and interstitial lung disease. Previously reported radiographic lung findings include ground-glass opacification, streaky infiltrates, and interstitial septal thickening. We report here the unusual case of a newborn who rapidly developed large rounded masses in the lung soon after birth that then resolved spontaneously by 3 months of age. She was found to be a compound heterozygote for both a known and a novel mutation in the ABCA3 gene. This report underscores the diverse clinical presentation of this condition.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Neoplasias Pulmonares/genética , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Nódulo Pulmonar Solitario/genética , Autopsia , Biopsia con Aguja , Progresión de la Enfermedad , Resultado Fatal , Femenino , Regulación Neoplásica de la Expresión Génica , Ventilación de Alta Frecuencia/métodos , Humanos , Inmunohistoquímica , Recién Nacido , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Mutación , Radiografía Torácica , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Medición de Riesgo , Nódulo Pulmonar Solitario/patología , Nódulo Pulmonar Solitario/terapia , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To characterize inheritance of homozygous, rare, recessive loss-of-function mutations in surfactant protein-B (SFTPB) or ATP binding cassette, subfamily A, member 3 (ABCA3) genes in newborns with lethal respiratory failure. STUDY DESIGN: We resequenced genes from parents whose infants were homozygous for mutations in SFTPB or ABCA3. For infants with only 1 heterozygous parent, we performed microsatellite analysis for chromosomes 2 (SFTPB) and 16 (ABCA3). RESULTS: We identified 1 infant homozygous for the g.1549C > GAA mutation (121ins2) in SFTPB for whom only the mother was heterozygous and 3 infants homozygous for mutations in ABCA3 (p.K914R, p.P147L, and c.806_7insGCT) for whom only the fathers were heterozygous. For the SP-B-deficient infant, microsatellite markers confirmed maternal heterodisomy with segmental isodisomy. Microsatellite analysis confirmed paternal isodisomy for the 3 ABCA3-deficient infants. Two ABCA3-deficient infants underwent lung transplantation at 3 and 5 months of age, respectively, and 2 infants died. None exhibited any nonpulmonary phenotype. CONCLUSIONS: Uniparental disomy should be suspected in infants with rare homozygous mutations in SFTPB or ABCA3. Confirmation of parental carrier status is important to provide recurrence risk and to monitor expression of other phenotypes that may emerge through reduction to homozygosity of recessive alleles.