Pulmonary alveolar proteinosis in children on La Réunion Island: a new inherited disorder?

Orphanet J Rare Dis. 2014 Jun 14:9:85. doi: 10.1186/1750-1172-9-85.

Abstract

Background: Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Réunion Island.

Methods: Data were retrospectively collected from medical files. Radiological and pathological elements were reviewed by two pediatric radiologists and three pathologists, respectively.

Results: Thirteen cases were familial and 32/34 (94%) cases were family connected. Disease onset occurred in the first six months of life in 82% of the patients. Thoracic computed tomography scans showed the typical "crazy-paving" pattern in 94% of cases. Respiratory disease was associated with a liver disorder, with the detection of liver enlargement at diagnosis in 56% of cases. The course of the disease was characterized by frequent progression to chronic respiratory insufficiency, accompanied by the appearance of cholesterol granulomas and pulmonary fibrosis. Overall prognosis was poor, with a mortality of 59% and an overall five-year survival rate from birth of 64%. Whole-lung lavages were performed in 21 patients, with no significant effect on survival. Liver disease progressed to cirrhosis in 18% of children, with no severe complication.

Conclusions: PAP in children from la Réunion Island is characterized by an early onset, associated liver involvement, poor prognosis and frequent progression to lung fibrosis, despite whole-lung lavages treatment. The geographic clustering of patients and the detection of many familial links between most of the cases strongly suggest a genetic etiology, with an autosomal recessive mode of inheritance.

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • France
  • Humans
  • Infant
  • Male
  • Pedigree
  • Pulmonary Alveolar Proteinosis / diagnosis*
  • Pulmonary Alveolar Proteinosis / diagnostic imaging
  • Pulmonary Alveolar Proteinosis / genetics
  • Radiography
  • Retrospective Studies