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Ultrastructural and biochemical studies were performed on a biopsy from the cerebral cortex of a child with late infantile amaurotic idiocy. The disease began clinically at 26 months of age with intellectual and behavioral deterioration and progressive blinijness resulting from pigmentary degeneration of the retina. The cytoplasm olf neurons was distended by material that stained intensely in periodic acid-Schiff preparations, and ultrastructural studies showed many abnormal membrane-bound cytosomes. Although concentrations of lipid-bound sialic acid were normal, showing only minor changes in the ganglioside pattern, riondialyzable sialoglycoproteins were strikingly increased. Biochemical characterization of some forms of amaurotic familial idiocy may be dependent on increasing knowledge of metabolic interrelations between sialoglycopiroteins and gangliosides.

Circulating blood lymphocytes from two patients with neuronal ceroid-lipofuscinosis (NCL) were investigated by transmission electronmicroscopy. Ultrastructural examination showed two forms of intracytoplasmic single membrane-limited inclusions. Contents of the first inclusion form were arranged in five distinct patterns: (1) granules, (2) membranous formations, (3) paracrystalline forms, (4) alternating electron-dense/electron-lucent arrangements, and (5) admixtures of these components. These molecular morphologies suggest the usefulness of lymphocyte fine structure as a diagnostic tool in NCL. The second inclusion form contained cylinder-like structures. These structures are not specific for NCL and have been identified in other diseases.

We used ultracentrifugation to isolate autofluorescent storage particles from the brains of patients with infantile type of neuronal ceroid lipofuscinosis (Haltia-Santavuori). The particles differed from those of the late infantile (Jansky-Bielschowsky) and juvenile (Batten-Spielmeyer-Sjögren) types and retained the characteristic appearance--large, partly membrane-bound conglomerates of spherical globules with a uniform finely granular internal structure--despite the vigorous procedure. The sedimentation properties of the particles also differed from the two other forms, but dolichols are found in the particles of all three diseases.

This is a report of a new familial neurologic disorder characterized by ceroid-lipofuscin storage, sea-blue histiocytes, and associated neurologic findings. Neurologic manifestations in the family members examined were varied, but posterior column involvement was the most common finding. The presence of sea-blue histiocytes was genetically determined by an autosomal dominant trait. Vitamin E blood concentrations were decreased in the absence of absorption difficulties in two sisters who were most seriously affected. The relationship of ceroid-lipofuscin, lipid peroxidation, and vitamin E is discussed.

Neuronal ceroid-lipofuscinosis is manifested by visual and intellectual deterioration and seizures. Autofluorescent lipopigments are found in neural and many nonneural tissues, with characteristic staining and ultrastructural properties. Presumptive diagnosis can usually be made on the basis of history, physical examination, and electrodiagnostic tests, but in the absence of a specific biochemical defect, histologic confirmation is essential. A 6-year-old boy with the clinical appearance of the juvenile form of the disease had sea-blue histiocytes in the bone marrow. And curvilinear profiles in ultrastructural inclusions in skin biopsy tissue, cultures skin fibroblasts, and bone marrow cells.

We describe the clinical, pathologic, and ultrastructural findings in a case of juvenile onset neuronal ceroid-lipofuscinosis without visual symptoms or retinal abnormalities. The histochemical and ultrastructural characteristics of the neuronal lipopigment were similar to those in typical cases of neuronal ceroid-lipofuscinosis. Atypical neuronal ceroid-lipofuscinosis may be distinguished histochemically, ultrastructurally, and clinically from another disorder called juvenile dystonic lipidosis, with which it has been confused.

SUMMARYA previously reported case of juvenile G M2 -gangliosidosis was reinvestigated enzymatically with cellulose acetate electrophoresis. There was a partial deficiency of hexosaminidase component A, in contrast to the complete absence of this component in classical infantile G M2 -gangliosidosis (Tay-Sachs disease) and to the complete loss of both components A and B in a case of total hexosaminidase deficiency. Juvenile G M2 -gangliosidosis, therefore, may be tentatively characterized as partial hexosaminidase A deficiency, although this partial deficiency may be the result of complete deficiency of one or more specific subcomponents not yet identified within “component A” of hexosaminidase.

A clinically unique case of ceroid-Iipofuscinosis is described with a juvenile onset, severe chorea that dominates the clinical picture, absence of retinal changes, and uniform intraneuronal inclusions consisting of curvilinear bodies. Cerebral biopsy was performed and ultrastructural and histochemi-cal studies were made. This case differs clinically from the classic late infantile type of nonglycolipid neuronal storage disorder and it differs clinically and ultrastructurally from the classic juvenile type with pigmentary degeneration of the retina. Several atypical variants without visual loss have been reported, but this case appears morphologically distinct from the few cases with a dystonic form recently described ultrastructurally. It supports the notion of nosologic heterogeneity among the nonglycolipid neuronal storage disorders.

Article abstract Two labeled steroid conjugates, 1 14 C]-dehydroepiandrosterone-3-beta-N-acetylglucosaminide and [9 4 C]-testosterone-17-beta-N-acetylgluco-saminide, were used to assay the steroid-hexosaminide cleaving activity of liver preparations from patients with Tay-Sachs disease, Sandhoff-Jatzkewitz disease, and the AB variant. The results were compared with those obtained with normal controls. The steroid hexosaminidase activity was directly proportional to the artificial substrate cleaving activity (4-methylumbelliferyl-beta-D-N-acetylglucosaminide) in both the A and B components of beta-N-acetylhexosaminidase. The constant ratio of specific enzymatic activities towards the three substrates in each case examined suggests that the same enzymes are active toward all three substrates. In spite of the decreased steroid hexosaminidase activity in Sandhoff-Jatzkewitz disease, no increased excretion of steroid hexo-saminides was observed in the urine of patients with this disease.

A woman had a progressive neurologic syndrome beginning at age 3 and lasting for three decades. Clinical manifestations included severe mental deterioration, spastic paralysis, myoclonus, and tremors. A postmortem examination showed ubiquitous infiltration of neurons by lipofuscin and deposits of pigment in the globus pallidus and substantia nigra, as well as senile changes of nerve cells. Biochemical investigation of brain lipids showed an alteration of fatty acid composition of serine phosphoglycerides.

A 43-year-old man presented with splenomegaly and a 20-year history of a neurologic disorder that included vertical supranuclear ophthalmoplegia, mild dementia, and a movement disorder. Adult dystonic lipidosis was diagnosed from the clinical picture and demonstration of foamy and sea-blue histiocytes in bone marrow. Ultrastructural patterns in cytolysosomes suggested accumulation of neutral fat and phospholipids. Liver content of bis-(monoacylglycerol) phosphate was increased, probably because the number of lysosomes had increased. Sphingomyelinase activity was normal in cultured skin fibroblasts. Juvenile and adult dystonic lipidosis form a clinically, histologically, and biochemically distinct neurovisceral storage disease that differs from Niemann-Pick disease.

In 13 patients with morphologically established juvenile neuronal ceroid lipofuscinosis and 13 controls, the activity of leukocyte peroxidase (myeloperoxidase) was determined under various conditions: Measurement of water-soluble enzyme, the buffer-soluble enzyme, and the 1euk.ocyte homogenate; application of phosphate buffer (pH 7.0) and borate buffer (pH 7.6); employment of 9 mM, 28 mM, and 55 mM p -phenylenediamine as hydrogen donor; and measurement of the specific enzyme extinction at 10,60, and 180 seconds. A significant difference between mean values for patients and controls could not be established. In both groups, single individuals exhibited definitely increased or reduced enzyme concentrations, leaving us, however, without an adequate explanation for these observations. Our studies indicate that determination of myeloperoxidase has no value in establishing the diagnosis of neuronal ceroid-lipofuscinoses.