[Hepatobiliary disorders in chronic nonspecific intestinal inflammation]. / Hepatobiliární postizení u chronických nespecifických strevních zánetu.

In 1977-1992 chronic inflammatory bowel disease was diagnosed in the gastroenterological department at the Clinic of Pediatrics in 31 children. Idiopathic proctocolitis was diagnosed in 16 children--mean age at the time of diagnosis was 13 years and 9 months. Fifteen children were treated for the diagnosis of Crohn's disease. Their mean age was 12 years and 9 months. During the investigation period all patients were examined regularly with special attention to hepatobiliary disease. Elevated aminotransferase values were observed in four children, three of these children have had permanent elevation of aminotransferase. Percutaneous liver biopsy revealed chronic persistent or active hepatitis. The authors investigated the course of the liver disease in relation to GIT disease. In the discussion they analyze the incidence, etiopathogenesis and type of liver lesions in inflammatory bowel disease with regard to the case-histories of their three patients.

Liver findings in Niemann-Pick disease type C.

A complex analysis of liver from a series of eight cases of Niemann-Pick disease type C showed practically generalized storage of glycolipids and phosphoglycerides by chemical and histochemical techniques. In six of the eight cases the storage process was of low degree, barely recognizable by routine histology, but well recognizable by histochemistry and electron-microscopy. In two cases it was marked and led to early functional impairment of the liver. Changes in various enzyme activities and in ultrastructural features of the storage process are described. Sphingomyelin was found to participate to a very low low degree and its accumulation was not proportional to the extent of overall storage. In two cases with prominent involvement of the liver normal levels of sphingomyelin were found. In other cases sphingomyelin was found, by lipid histochemistry, to be stored only in macrophages. To stress that the storage process in Niemann-Pick disease type C is qualitatively different a comparison was made with liver findings in sphingomyelinase-deficient patients. This feature is of practical as well as theoretical importance.

Niemann-Pick disease: lipid storage in bone marrow macrophages.

A histochemical study of lipids in bone marrow smears was performed in a series of 15 cases of Niemann-Pick disease (NPD). It revealed significant differences in the amount of lipids stored in macrophages of sphingomyelinase (SMase) deficiency (types A, B) and type C. Early deposition of uniform, anisotropic droplets of sphingomyelin (Maltese-cross birefringence) in lysosomes was a feature of a 9-member group of SMase deficiency (types A, B). The type C group (six cases) was characterized by a remarkable difference in the degree of phospholipid, mainly sphingomyelin, deposition. The total amount of phospholipids was small on average, and very often inversely proportional to pronounced structural storage changes. This indirect relationship was most prominent in the early phase of the disease and grew less prominent as the disease progressed further. The stored lipid was primarily isotropic. In longer lasting cases of both categories (SMase deficiency and type C) a considerable part of the storage cell population displayed ceroid deposition giving the appearance of a 'sea-blue histiocyte' independent of the type of NPD, but with definite predominance in SMase deficiency. The diagnostic value of the findings is discussed, and some pathogenetic conclusions suggested, particularly as regards type C. Lipid histochemistry of bone marrow smears is highly recommended as it represents a simple but highly efficient approach, capable of yielding valuable diagnostic information.

Niemann-Pick disease (variation in the sphingomyelinase deficient group). Neurovisceral phenotype (A) with an abnormally protracted clinical course and variable expression of neurological symptomatology in three siblings.

We report three families with five cases of sphingomyelinase (SMase) deficiency, early neurovisceral symptomatology, and a conspicuously protracted course (7-22 years) in contrast to the characteristic acute, rapidly lethal course in classical type A cases. Most of the visceral symptoms were hepatomegaly and splenomegaly, with numerous foam cells in the bone marrow, some of them containing ceroid (sea-blue histiocytes). Histochemical and chemical biopsy studies (liver, skin, bone marrow) revealed macrophage and epithelial sphingomyelinosis and profound SMase deficiency. The dominant neurological symptoms in three of the cases included extrapyramidal involvement, marked mental deficiency, and cherry red spots in the fundus oculi of all the 5 cases. There was, however, a striking variability in the clinical signs in three siblings. The first of them, a girl, died at 7 years from purely visceral involvement with massive affection of the lungs. Despite the absence of clinically detectable, neurological symptomatology there was discrete regional neuronal storage in the brain. Her two younger brothers are still alive. The elder one (22 years) has been reduced to complete neurological invalidism while his younger brother (18 years) has no demonstrable neurological changes, and enjoys normal social integration. Symptomatologically, he is difficult to distinguish from type B, especially from its rare variants with retinal involvement. The discussion is devoted to differences between types A and B of the SMase deficiency and to the neurological symptomatology apparently independent of the gene dose in the three siblings.