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A female patient is described with highly echogenic splenic nodes found in routine diagnosis. After CT and angiography a splenectomy was carried out. The histological finding of sea blue histiocytes and the extended family history suggested a subtype of Niemann-Pick disease. Biochemical lipid analysis of the spleen confirmed Type-C Niemann-Pick disease. Niemann-Pick disease and its subtypes are discussed briefly.

Amniocentesis in the 17th week of pregnancy in a 23-year-old woman who had previously lost a child with enzymatically proven Krabbe's disease revealed normal activity in cell-free amniotic fluid. But in two amniotic cell cultures a 25% defect of cerebroside-beta-galactosidase was found. The prenatal diagnosis of Krabbe's disease was subsequently confirmed after abortion of the fetus by enzymatic and morphological examination (globoid cells in the spinal-cord sections).

A brain biopsy obtained from a twenty-eight month old boy with ceroidlipofuscinosis was studied by light and electron microscopy. There were widespread intracellular deposits of autofluorescent material taking the fat stains. Cytoplasmic inclusions were plentiful in neurons, astrocytes, oligocytes, M cells and vascular elements. Their substructure ranged from that of variably dense aggregates of essentially homogeneous or granular appearance to that of miscellaneous collections of lamellar pairs and/or tubular structures of variable length. Stacks of 2 to 4 linear profiles with a curved outline were rarely seen and then almost exclusively inside cytosomes of endothelial cells. Similar observations were made in peripheral nerve, skin and liver biopsies. The granules of peripheral blood neutrophilic leukocytes were unremarkable. A small percentage of lymphocytes contained granular cytoplasmic bodies not unlike those known to be an ordinary feature of some lymphocytes of the average blood sample. However, a certain resemblance between these bodies and some of the cytosomes seen in the patient's tissues was also apparent. Myeloperoxidase activity was tested with paraphenylenediamine and was found to be normal on two occasions. The patient's age, cytosome morphology and distribution and results of peroxidase assay add special interest to this case of generalized ceroidlipofuscinosis. However, none of these features, either singly or in combination, warrants creation of a distinct subtype within this group of disorders. Myeloperoxidase deficiency is probably just another phenotypical marker of some patients with generalized ceroidlipofuscinosis rather than the genetic defect of Batten disease.

A 36-year-old woman was admitted for hepatosplenomegaly and anemia. Bone marrow cytology showed "sea-blue histiocytes", vacuolated macrophages and plasma cells. As primary liver disease, malignancy or hematologic disorders were excluded, and plasma chitotriosidase activity was increased 27-fold over control, the presence of a lysosomal storage disease was suspected. Biochemical analysis of skin fibroblasts revealed normal glucocerebrosidase and sphingomyelinase activity, but lipid analysis showed a more than 15-fold accumulation of cholesterol esters within the cells. The activity of lysosomal acid lipase (LAL) in fibroblast homogenates was decreased to 12% of control subjects. Mutational analysis of the patient's blood showed the homozygous G-->A mutation at position -1 of the exon 8 splice donor site (E8SJM-allele) known for adult cholesteryl ester storage disease (CESD); the polymorphic background was that of the complex haplotype -6Thr, 2Gly, 894 G-->A. Based on clinical, laboratory, cytological and and biochemical findings, CESD can clearly be separated from other more frequent inherited lysosomal storage diseases, e.g. atypical forms of Gaucher disease