Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy.
Am J Respir Crit Care Med
; 182(10): 1292-304, 2010 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-20622029
ABSTRACT
RATIONALE We identified a 6-year-old girl with pulmonary alveolar proteinosis (PAP), impaired granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor function, and increased GM-CSF. OBJECTIVES:
Increased serum GM-CSF may be useful to identify individuals with PAP caused by GM-CSF receptor dysfunction.METHODS:
We screened 187 patients referred to us for measurement of GM-CSF autoantibodies to diagnose autoimmune PAP. Five were children with PAP and increased serum GM-CSF but without GM-CSF autoantibodies or any disease causing secondary PAP; all were studied with family members, subsequently identified patients, and controls. MEASUREMENT AND MAINRESULTS:
Eight children (seven female, one male) were identified with PAP caused by recessive CSF2RA mutations. Six presented with progressive dyspnea of insidious onset at 4.8 ± 1.6 years and two were asymptomatic at ages 5 and 8 years. Radiologic and histopathologic manifestations were similar to those of autoimmune PAP. Molecular analysis demonstrated that GM-CSF signaling was absent in six and severely reduced in two patients. The GM-CSF receptor ß chain was detected in all patients, whereas the α chain was absent in six and abnormal in two, paralleling the GM-CSF signaling defects. Genetic analysis revealed multiple distinct CSF2RA abnormalities, including missense, duplication, frameshift, and nonsense mutations; exon and gene deletion; and cryptic alternative splicing. All symptomatic patients responded well to whole-lung lavage therapy.CONCLUSIONS:
CSF2RA mutations cause a genetic form of PAP presenting as insidious, progressive dyspnea in children that can be diagnosed by a combination of characteristic radiologic findings and blood tests and treated successfully by whole-lung lavage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteinose Alveolar Pulmonar
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Doenças Genéticas Inatas
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article