This has been recognized in the settings of certain cancers (such as myeloid leukemia), lung infections, or environmental exposure to dusts or chemicals, such as nickel.Although the cause of PAP was not originally understood, a major breakthrough in the understanding of the cause of the disease came by the chance observation that mice bred for experimental study to lack a hematologic growth factor known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome of abnormal surfactant accumulation resembling human PAP.The implications of this finding are still being explored, but significant progress was reported in February 2007. Researchers in that report discussed the presence of anti-GM-CSF autoantibodies in patients with PAP, and duplicated that syndrome with the infusion of these autoantibodies into mice.Familial or sporadic inactivating mutations in one of the two parental GATA2 genes produces an autosomal dominant disorder termed GATA2 deficiency. The GATA2 gene produces the GATA2 transcription factor which is critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming cells. Individuals with a single GATA2 inactivating mutation present with a wide range of disorders including pulmonary alveolar proteinosis. GATA2 mutation-based pulmonary alveolar proteinosis is associated with normal levels of GM-CSF and commonly improves or is avoided in afflicted individuals who successfully receive a hematopoietic stem cell transplantation. Genetics
Hereditary pulmonary alveolar proteinosis is a recessive genetic condition in which individuals are born with genetic mutations that deteriorate the function of the CSF2 receptor alpha on alveolar macrophages.
Autosomal dominant (IMB3; OMIM 605637 [1]) and autosomal recessive (IBM2; OMIM 600737 [2]) forms have been described. The autosomal recessive form, first characterized in Jews of Persian descent, is a myopathy that affects mainly leg muscles, but with an unusual distribution that spares the quadriceps, so-called quadriceps-sparing myopathy (QSM). This disorder was subsequently found in other Middle Eastern families, the gene was mapped to 9p13-p12, and in 104 affected persons from 47 Middle Eastern families the same mutation in homozygous state was found in the GNE gene. Affected individuals in families of other ethnic origins were found to be compound heterozygotes for other distinct mutations in the GNE gene. From OMIM 603824. [3]

See also
Inclusion body myositis, a more common and non-hereditary form. Valosin-containing protein (VCP); mutations in VCP cause multisystem proteinopathy (MSP) which can present (among others) as a rare form of inclusion body myopathy. References
External links
GeneReviews/NCBI/NIH/UW entry on Inclusion Body Myopathy 2
GeneReviews/NCBI/NIH/UW entry on Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia