Primary Familial Xanthomatosis With Involvement and Calcification of the Adrenals

Abstract

THIS PAPER deals with the description of clinical, pathologic, histochemical and biochemical findings in two cases of generalized xanthomatosis with calcification of the adrenals. The infants were siblings of a previously described patient,1 and and the findings warrant the conclusion that the disease process was identical in all three. The study of these cases and review of pertinent literature indicates that primary xanthomatosis (idiopathic lipidosis with deposition of cholesterol and triglycerides) is a metabolic disease entity that is independent of the granulomatous process called histiocytosis X, or eosinophilic xanthomatous granuloma. It will be shown in the discussion that primary xanthomatosis may occur in various forms, and that the form described in this paper is a rare but distinct clinical and pathologic type. This type differs in the distribution of lesions from other types of primary xanthomatosis, such as the type of cerebral xanthomatosis described by van Bogaert, Scherer and Epstein, and the type associated with involvement of bones that sometimes produces the Hand-Schüller-Christian syndrome. For reasons that wiil be clarified in the discussion, the term "Hand-Schüller. Christian disease" is not adopted in this paper. The term "Hand-Schüller-Christian syndrome" indicates a well-known syndrome with exophthalmos, diabetes insipidus and peculiar bone changes. The term "primary xanthomatosis" describes a primary (i.e., idiopathic) storage process in which triglycerides and cholesterol are deposited in various tissues. CASE REPORTS Case 1 Family History: The two infants described in this article and the infant previously described1 were female siblings born to closely related parents. The father and mother, both Persian Jews, were cousins.

Wolman's Disease: A Rare Cause of Infantile Cholestasis and Cirrhosis

“…Moshe Wolman first described the condition in 1956 of three siblings born consanguineously. 2 A mutation causes it on the LIPA gene and the spectrum of LAL-D can vary from WD which is a severe variant presenting in early infancy to a chronic variant called cholesteryl ester storage disorder (CESD). 1 In WD, the levels of lysosomal acid lipase activity are less than 1%, whereas in CESD, there is a residual enzyme activity varying from 1 to 12%, correlating with the clinical presentation of these two entities.…”

Clinical and Histologic Liver Improvement in Siblings With Lysosomal Acid Lipase Deficiency After Enzyme Replacement

“…The variable rate of onset and severity of the disease is presumed to be the result of the different disease-causing mutations in the LIPA gene, which encodes for lysosomal acid lipase (LAL), causing various degrees of impaired enzyme activity (5). Infants with WD have absent or less than 1% of normal LAL activity, and present within the first few weeks of life with vomiting, diarrhea, pyrexia, abdominal distention, hepatosplenomegaly, and failure to thrive (1,6,7). About 50% have adrenal calcification.…”

Lysosomal Acid Lipase Deficiency in Libya: A Case Report

“…Wolman disease (WD) is a rare and severe subtype of LAL deficiency, characterized by nearly absent LAL activity [1]. The first three sibling cases were documented in 1956 by physician Moshe Wolman [2]. Children with this mutation accumulate cholesteryl esters and triglycerides in various tissues throughout the body resulting in a spectrum of clinical manifestations like failure to thrive and liver damage.…”