MORBID ANATOMY, HISTOLOGY AND PATHOGENESIS OF LIGNAC‐FANCONI DISEASE: (Cystine Storage Disease with Aminoaciduria)

Abstract

Summary Detailed gross anatomical and histopathological findings in six cases of Lignac‐Fanconi disease are described and discussed. An attempt is made to present the natural history of individual organ changes, particularly those of the kidney. It is interesting to note that the disease in its early stages can occur without kidney changes. The bone changes are essentially rachitic; there is no feature of the histopathology of the bones which is not met with in rickets, particularly in “rachitis tarda.” Bone changes suggestive of hyperpara‐thyroidism are not conspicuous in this disease. The parathyroids were markedly hypertrophic in two of our cases; hypertrophy in other cases cannot be excluded. The phosphatase reaction was negative in all kidneys examined, reduced in liver, spleen and bone‐marrow but normal in the small intestine. Negative phosphatase reaction in the kidney has also been found in chronic inflammatory kidney disease and is not specific for Lignac‐Fanconi disease. Methods for demonstration and identification of cystine crystals in tissue sections, bone‐marrow films and lymph node imprints are described, together with experiments which account for the difference between the crystallographic appearance of cystine in tissues and cystine crystallised from aqueous solutions. In our opinion a lymph node biopsy is the most reliable procedure for a definite diagnosis of Lignac‐Fanconi disease in vivo , though bone‐marrow sections and/or films are usually sufficient for the purpose. The intracellular localisation of cystine crystals is stressed, and histopathological and experimental evidence is given for the assumption that cystine storage is not due to phagocytosis, but that cystine crystallises at the site of its formation, namely in a certain part of the reticuloendothelial system. A critical review is given of various hypotheses concerning the pathogenesis of Lignac‐Fanconi disease. The hypothesis is put forward that Lignac‐Fanconi disease is a disorder of protein metabolism, probably of its anabolic phase. As a disorder of intracellular metabolism, the disease is likened to true lipidoses.