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

Laurent Enaud1, Alice Hadchouel23*, Aurore Coulomb4, Laureline Berteloot5, Florence Lacaille6, Liliane Boccon-Gibod4, Vincent Boulay7, Françoise Darcel8, Matthias Griese9, Mélinée Linard10, Malek Louha11, Michel Renouil1, Jean-Pierre Rivière12, Bruno Toupance13, Virginie Verkarre14, Christophe Delacourt23 and Jacques de Blic23

Author Affiliations

1 CHU Sud Réunion, service de Pédiatrie, Saint-Pierre, La Réunion, France

2 Service de Pneumologie Pédiatrique, AP-HP, Hôpital Necker-Enfants Malades, service de Pneumologie Pédiatrique, Centre de Référence pour les Maladies Respiratoires Rares de l’Enfant, 149-161 rue de Sèvres, 75015 Paris, France

3 Université Paris-Descartes, Paris, France

4 AP-HP, CHU Paris-Est Hôpital d’Enfants Armand Trousseau, service d’Anatomie et Cytologie Pathologiques, Paris, France

5 AP-HP, Hôpital Necker-Enfants Malades, service de Radiologie Pédiatrique, Paris, France

6 AP-HP, Hôpital Necker-Enfants Malades, service de Gastroentérologie Pédiatrique, Paris, France

7 CHU Sud Réunion, service de Pneumologie, Saint-Pierre, La Réunion, France

8 CHU Sud Réunion, service de Neurologie, Saint-Pierre, La Réunion, France

9 Hauner Children’s University Hospital, Ludwig-Maximilians-University, Member of the German Center for Lung Research, Munich, Germany

10 CHU Sud Réunion, Service de Radiologie, Saint-Pierre, La Réunion, France

11 AP-HP, CHU Paris-Est Hôpital d’Enfants Armand Trousseau, laboratoire de Biochimie et Biologie Moléculaire, Paris, France

12 CHU Nord Réunion, service d’Anatomie et Cytologie Pathologiques, Saint-Denis, La Réunion, France

13 Eco-Anthropologie et Ethnobiologie, UMR 7206 CNRS, MNHN, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France

14 AP-HP, Hôpital Necker-Enfants Malades, service d’Anatomie et Cytologie Pathologiques, Paris, France

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Orphanet Journal of Rare Diseases 2014, 9:85  doi:10.1186/1750-1172-9-85

Published: 14 June 2014

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.

Keywords:
Pulmonary alveolar proteinosis; Pulmonary fibrosis; Child; Liver disease