INTERSTITIAL LUNG-DISEASE IN AN ADULT WITH FANCONI-ANEMIA - CLUES TO THE PATHOGENESIS

We have studied a 38-year-old man with a prior diagnosis of Holt-Gram syndrome, who presented with diabetes mellitus, He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-s ulfamethoxazole for sinusitis, Thrombocytopenia progressed to pancytop enia, The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA), Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32, A t age 38, computerized tomography showed bilateral upper lobe fibrosis , lower lobe honeycombing, and bronchiectasis. Pulmonary function test s, compromised at age 29, showed a moderately severe obstructive and r estrictive pattern by age 38, Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1, Karyotype was 46,XY wit h a marked increase in chromosome aberrations induced in vitro by diep oxybutane. The early onset and degree of pulmonary disease in this pat ient cannot be fully explained by environmental or known genetic cause s. The International Fanconi Anemia Registry (IFAR) contains no exampl e of a similar pulmonary presentation, Gene environment (ecogenetic) i nteractions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. (C) 1997 Wiley-Liss, Inc.