Niemann-Pick Disease

NIEMANN-PICK DISEASE (Niemann, Pick) (lipid cell splenomegaly-hepatomegaly type N.-P.), a rare congenital disease based on a violation of lipid metabolism. It was first described by Niemann in 1924 and studied in detail by Pick. N.-P. disease occurs only in early childhood (death occurs no later than the second year), is detected from the first weeks of life, and is characterized by sharp weight loss and a progressively increasing abdomen, which is based on enlargement of the spleen, liver, and sometimes a small ascites. Later, these symptoms are joined by enlargement of the lymph glands and yellowing of the skin, especially on open parts of the body. There are no deviations from normal in the urine. The blood picture is mostly unchanged, although sometimes leukocytosis is noted. In individual cases, hypercholesterolemia (up to 0.65%) is observed, in others it is absent. Death occurs with signs of progressive exhaustion, sometimes with diarrhea. At autopsy, a sharply enlarged fatty liver and a spleen of the same appearance are found, lemon-yellow, greatly enlarged external and internal lymph glands, enlarged adrenal glands with a wide bright yellow cortex and yellow medulla, and a yellowish color of almost all internal organs. Histological research reveals that in all, even macroscopically unchanged organs, the endothelium of capillaries, reticulo-endothelial elements, and cells of the connective tissue stroma are transformed into large (up to 20-80μ), round, mono- or binuclear formations ('cells of the Niemann-Pick type'), whose protoplasm in a section has a foamy appearance, while in the fresh state (from a punctate) it appears filled with numerous shiny grains, some of which give double refraction; all are well stained with fat dyes (Sudan III, osmium, Nilblausulfate, etc.), and most of them give a sharply positive reaction according to the Smith-Dietrich method, staining black-blue in the process. The data of microchemical research thus indicate that the substances deposited in the 'cells of type N.-P.' are lipids, mainly phosphatides, to a lesser extent - cholesterol, cholesterol esters, and neutral fats. Lipids of the same quality can also be found in muscle fibers of the heart, skeletal muscles, in the epithelium of all secreting glands, in the cells of internal secretion organs and egg follicles, in ganglion and glial cells of the nervous system, and in Schwann sheath cells. Chemical (quantitative) analysis confirms the microchemical data. It shows, for example, that in the spleen tissue in N.-P. disease, the total amount of lipids far exceeds the norm (11.6-16.0% against normal 1.1-4.25%), with the main mass falling on phosphatides, resp. lecithin (6.4-10.3% against normal 0.08-1.82%), and only a smaller part - on cholesterol and its esters. The widespread lipophagia by the most diverse cellular elements obviously indicates that the basis of the disease is a primary violation of lipid metabolism; the data of microchemical and chemical research in turn reveal that the main changes consist in a violation of phosphatide metabolism. This circumstance allows to clearly delimit N.-P. disease from other morphologically somewhat similar forms of so-called visceral xanthomatosis: from Gaucher's disease (see Gaucher disease), in which kerasin is deposited in reticulo-endothelial elements, and from Schüller-Christian disease, which in the prevalence of lipid deposits closely approaches N.-P. disease, but in which cholesterol and cholesterol esters accumulate predominantly in lipophages. Taking into account the absence of any exogenous factors to which one could attribute a role in the origin of this disease, its congenital and familial nature (with healthy parents) and its great rarity (which excludes the possibility of accidental coincidence in several members of one family), it should be recognized that N.-P. disease is a genotypic trait, conditioned by a recessive autosomal gene. Both boys and girls get sick with it; only some predominance of the latter is noted. N.-P. disease is most common among the Jewish population. It is noteworthy that N.-P. disease is often combined with the Tay-Sachs form of amaurotic idiocy. The diagnosis can be facilitated by puncture of the spleen and histological examination of the punctate. As therapeutic intervention, splenectomy was tried, however without success. The prognosis is absolutely poor.