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Successful haematopoietic stem cell transplantation in a case of pulmonary alveolar proteinosis due to GM-CSF receptor deficiency
  1. Marie-Louise Frémond1,2,3,
  2. Alice Hadchouel2,4,5,
  3. Cyril Schweitzer6,7,
  4. Laureline Berteloot8,
  5. Julie Bruneau2,9,10,
  6. Cécile Bonnet11,
  7. Guilhem Cros1,
  8. Coralie Briand1,
  9. Alessandra Magnani12,13,
  10. Cécile Pochon14,
  11. Christophe Delacourt2,4,
  12. Marina Cavazzana2,12,13,
  13. Despina Moshous1,2,15,
  14. Alain Fischer1,2,10,16,
  15. Stéphane Blanche1,2,
  16. Jacques De Blic2,4,
  17. Bénédicte Neven1,2,17
  1. 1Paediatric Haematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France
  2. 2Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France
  3. 3Laboratory of Neurogenetics and Neuroinflammation, INSERM UMR 1163, Paris, France
  4. 4Paediatric Pneumology Department, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
  5. 5INSERM U955, Créteil, France
  6. 6Department of Médecine Infantile, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-les-Nancy, France
  7. 7DeVAH EA 3450, Villers-lès-Nancy, France
  8. 8Paediatric Radiology Department, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
  9. 9Pathology Department, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
  10. 10INSERM UMR 1163, Paris, France
  11. 11Genetic Department, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-les- Nancy, France
  12. 12Biotherapy Department, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
  13. 13Laboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, France
  14. 14Paediatric Oncology and Haematology Department, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-les-Nancy, France
  15. 15Laboratory of Genome Dynamics in the Immune System, INSERM UMR 1163, Paris, France
  16. 16Collège de France, Paris, France
  17. 17Laboratory of Immunogenetics of Pediatric Autoimmunity, INSERM UMR 1163, Paris, France
  1. Correspondence to Professor Bénédicte Neven, Paediatric Haematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, Paris F-75015, France; benedicte.neven{at}aphp.fr

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Cyril Schweitzer (CS): A 1.5-year-old girl was referred to the Paediatric Pneumology Department of the University Hospital of Nancy, France, for progressive tachypnoea and hypoxia. She suffered from intrauterine growth retardation, and was born prematurely at 31 weeks’ gestation; birth weight: 1.160 kg (≤2 SD); birth length: 37 cm (≤2 SD). The patient presented with acute respiratory distress syndrome at birth, requiring treatment with a dose of surfactant, 9 days of mechanical ventilation and 8 weeks of oxygen therapy. On arrival to our centre, she was dyspnoeic on exertion and oxygen saturations were between 91% and 94%. Further investigations included a high-resolution CT scan and a bronchoalveolar lavage (BAL).

Laureline Berteloot (LB) and Julie Bruneau (JB): CT imaging of the chest revealed a ‘crazy paving’ pattern whereas analysis of BAL fluid failed to identify any underlying disease.

CS: Hypoxia transiently improved after initiation of inhaled corticosteroids and antireflux therapy but relapsed after a few months, so that a second BAL was performed.

JB: The second BAL fluid revealed the presence of extracellular lipid and protein deposits and foamy alveolar macrophages.

CS and Cécile Bonnet (CeB): These abnormalities led to a diagnosis of pulmonary alveolar proteinosis (PAP) at the age of 2.6 years, which was confirmed by genetic testing; complex chromosome abnormalities were detected, with (1) deletion of CSF2RA and CRLF2 on the X chromosome inherited from the mother, and (2) a de novo rearrangement of the paternal X chromosome, resulting in loss of both CSF2RA alleles.1

CS, Christophe Delacourt (CD) and Jacques De Blic (JDB): Recessive mutations in the α or β subunits of the granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R, encoded respectively by CSF2RA and CSF2RB) cause two subtypes of hereditary PAP.2 Impairment of GM-CSF-dependent surfactant clearance by alveolar macrophages leads to the progressive accumulation of surfactant in the alveolar space …

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