[Pulmonary phenotypes of inborn errors of metabolism]. / Manifestations pulmonaires des maladies héréditaires du métabolisme.

Inborn metabolic diseases or inborn errors of metabolism comprise a large number of rare and heterogeneous genetic diseases categorized in several subgroups depending on their pathophysiologic mechanisms. In this review, we focus on different metabolic diseases with respiratory symptoms in adults: lysosomal glycosphingolipidoses such as acid sphingomyelinase deficiency (Niemann-Pick types A and B disease), Gaucher, Fabry, Pompe diseases and mucopolysaccharidoses in general. We also address classical homocystinuria, which is a monogenic vascular disease, Hermansky-Pudlak syndrome, which is associated with disorders in the lysosomal-related-organelles, and lysinuric protein intolerance, which is due to an amino-acid transporter defect. Presentation and prognosis of these diseases are highly heterogeneous, and respiratory impairment may be central and prognostic. Many are primarily pediatric, and diagnoses are often delivered during childhood. Improved pediatric management has enabled better prognosis and new phenotype of the diseases in the adulthood. Some others can be diagnosed during adulthood. While some diseases call for specific, specialized treatment, all necessitate systematic multidisciplinary management. It is of paramount importance that a pneumologist be familiar with these phenotypes, most of which can benefit from early diagnosis and early therapeutic management with dedicated innovative treatments.

Hyperacute rejection following lung transplantation.

Although hyperacute rejection has been clinically and pathologically fully described in recipients of other solid organ transplants, to our knowledge, there have been no previous fully documented cases in recipients of lung transplants. This case of clinical hyperacute rejection is corroborated by a positive, donor-antigen-specific IgG-mediated lymphocytotoxic crossmatch (LXM), and demonstrated histopathologic, immunofluorescent, and electron microscopic features consistent with hyperacute rejection as described in other organs. Features of diffuse alveolar damage, neutrophilic infiltrates, and endothelial and epithelial damage with IgG-fluorescent staining within alveolar spaces and septae were demonstrated. The management of hyperacute rejection and its outcome are reviewed. Historically a pretransplant crossmatch is not considered a routine part of lung transplantation. The outcome of this patient suggests that LXM should be performed routinely prior to lung transplant in all patients with high panel-reactive antibodies, and should be performed whenever circumstances permit.

Occlusive coronary arteritis: a cause of early death in a cardiac transplant patient.

A patient died 5 months after undergoing cardiac transplantation. Endomyocardial biopsies performed prior to death showed no evidence of severe rejection. At autopsy, nonnecrotizing occlusive coronary arteritis was present. The intima of the coronary arteries contained numerous lymphocytes and plasma cells. Chronic rejection appeared to be responsible for the arteritis. The onset of coronary occlusive disease is insidious, and recognition depends on the performance of coronary arteriography, which is usually not done until the one-year follow-up. Early coronary arteriography is suggested to rule out occlusive coronary arteritis when cardiac allograft function is not satisfactory, even when the endomyocardial biopsy shows no evidence of rejection.

Effects of cyclosporine, azathioprine and prednisone on Kimura's disease and focal segmental glomerulosclerosis in renal transplant patients.

Nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS) is a common cause of renal failure leading to transplantation. Various immunosuppressive drugs, including cyclosporine, have been used in the treatment of FSGS with varying degrees of success. The patient described herein was afflicted with end stage renal disease secondary to steroid-resistant nephrotic syndrome due to FSGS with coexistent Kimura's disease. After kidney transplantation, the patient experienced a remission of both the Kimura's disease and the nephrotic syndrome in the native kidneys, leading to the resumption of renal function by the native kidneys in spite of severe transplant glomerulopathy. This case suggests that certain cases of FSGS without extensive interstitial disease may benefit from aggressive treatment with a combination of immunosuppressive drugs.