Juvenile Amaurotic Idiocy Research Articles

Karl Gustaf Torsten Sjögren and Sjögren-Larsson syndrome.

Karl Gustaf Torsten Sjögren (1896-1974) a Swedish psychiatrist and geneticist, was a pioneer of modern Swedish psychiatry. Sjögren studied medicine at the University of Uppsala. From 1932 to 1935, he was Head Physician and Director of Lillehagen Hospital in Gothenburg, and between 1935- 1945, he was physician-in-chief at the psychiatric department of Sahlgrenska Hospital in Gothenburg. Sjögren was professor of psychiatry at Karolinska Institutet from 1945 to 1961 and was elected to the Royal Swedish Academy of Sciences in 1951. Sjögren was an expert of psychiatry for the World Health Organization. Among his many contributions to medicine, he is credited for describing several medical conditions, which were later named after him, including Graefe- Sjögren syndrome, Marinesco-Sjögren syndrome, and Sjögren-Larsson syndrome (SLS). During his work on juvenile amaurotic idiocy, Sjögren forged a collaboration with Tage K.L. Larsson, a statistics lecturer at the University of Lund. Their study on the combination of oligophrenia, congenital ichthyosis, and spastic disorders in 1957 established the clinical and genetic profile of a new disease entity, later known as Sjogren-Larsson syndrome (SLS).

Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of glycosphingolipids including gangliosides.

Long chain base compositions of gangliosides containing mainly stearic acid could be determined without any chemical modification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry with delayed ion extraction (DE MALDI-TOF MS). The analytical results for the long chain base compositions of various samples of GM1 from the brain tissues of patients with different diseases at different ages confirmed that the proportion of d20:1 (icosasphingosine) and d20 (icosa-sphinganine) of the total sphingosine bases increased quickly until adolescent or adult age and then remained constant slightly exceeding 50%; this value was evidently higher than the proportion of d20:1 and d20 of GM1 in various adult mammalian brains. A long chain base composition of GM1 from the brain tissue of a patient with infantile type of GM1-gangliosidosis at 4y2m was abnormal and so was in two sibling patients with Spielmeyer-Vogt type of juvenile amaurotic idiocy at 19y and 21y in spite of that in the latter there was no accumulation of GM1 in the brain tissue. On the other hand, a patient with adult type of GM1 gangliosidosis at 66y showed a local accumulation of GM1 in the putamen and caudate nucleus, but its long chain base composition was found to be normal. It was of interest that the white matter of Eker rat with hereditary renal carcinoma contained a large amount of plasmalocerebroside as compared with the amount of cerebroside and sphingomyelin. The individual molecular species of plasmalocerebroside were identified by DE MALDI-TOF MS.

Perspective of biochemical research in the neuronal ceroid-lipofuscinosis.

The search for biochemical abnormalities in the neuronal ceroid-lipofuscinoses (NCL) or Batten disease was initiated with the discovery of normal levels of gangliosides in juvenile amaurotic idiocy. The primary goal of most biochemical studies has been to discover the unique biochemical marker for carriers and at-risk individual. Ceroid, the singular pathomorphologic trait of NCL, was isolated and shown to differ from a similar but normal product of aged cells, lipofuscin. In spite of the availability of stored product, the chemical analysis of ceroid has not elucidated the unique biochemical defect in the NCL, as has been the case for other lysosomal storage disorders. The NCL were thought to be a result of lipid peroxidation because ceroid is also found in disorders of impaired vitamin E metabolism or results from a diet deficient in the antioxidant, vitamin E. In addition, tissue analysis indicated losses of polyunsaturated fatty acids in affecteds and carriers, as well as the presence of a secondary product of lipid peroxidation, 4-hydroxynonenal, in affected and carrier NCL dogs. With the exception of a fluorescent compound isolated from retinal ceroid, studies aimed at discovering the disease-specific fluorophores of ceroid have been largely inconclusive. The discovery of elevated dolichols in urine and brain tissue of NCL patients led to another hypothesis, that the basic biochemical defect in NCL involved the metabolism of dolichols and retinoids. However, the more recent view is that dolichol metabolism is secondary to the unknown NCL lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac involvement in juvenile amaurotic idiocy--a specific heart muscle disorder. Histological findings in 13 autopsied patients.

Juvenile amaurotic idiocy (JAI) is a rare disorder of autosomal recessive inheritance. It belongs to the so called ceroid lipofuscinoses and the central nervous system is the largest organ. Only very few reports refer to the accumulation of lipopigment in the heart of JAI patients. This study describes the morphology of the heart from all 13 patients with JAI in Denmark who died within a seven year period; electrocardiographic findings are related to structural changes. All compartments of the heart were involved, including the conduction system. Not only very substantial deposition of lipopigment was found in the myocytes, but we have also observed striking amounts of calcium and cholesterol compounds indicating a restrictive type of heart muscle disorder. These structural changes are uniform from case to case. Because of the nature of the disease only rather poor information of the cardiac state is available in JAI patients. 11 patients showed some cardiac enlargement. In 6 patients abnormal P-waves were recorded in the ECG suggesting increased atrial and ventricular diastolic pressure. 2 patients had bradycardia, probably due to sinus node involvement, and one patient developed complete right bundle branch block. However, in the 4 patients in whom the cardiac conduction system could be examined histologically no evidence of disturbance of cardiac impulse formation and conduction was seen in the few standard ECG strips available in spite of extensive deposition of abnormal material throughout the conduction system. There seems to be a discrepancy between the relatively minor functional disturbances observed and the heavy morphological changes of the entire heart. This aspect, however, may well be altered by an intensified clinical observation and examination of JAI patients.

Acid hydrolases in serum from patients with lysosomal disorders

The activity of acid hydrolases was studied in serum from patients with mucolipidosis (II and III) and other lysosomal disorders. In mucolipidosis II and III all hydrolases examined except α-glucosidase, β-glucosidase and acid phosphatase were greatly increased. High values for β-galactosidase were seen in mucopolysaccharidosis types I and II, Gaucher's disease, juvenile amaurotic idiocy and metachromatic leucodystrophy. N-Acetyl- β-glucosaminidase activity was high in mucopolysaccharidosis types I, II, III and Gaucher's disease. The activity of β-glucuronidase was increased in mucopolysaccharidosis types I, II and III, Gaucher's disease, juvenile amaurotic idiocy and metachromatic leucodystrophy. Acid phosphatase had increased activity only in Gaucher's disease. In several lysosomal storage disorders no increased values could be found. It is suggested that high values in serum from patients with lysosomal storage disorders (not including mucolipidosis II and III) may depend upon liver cell damage, which disturbs the clearing of acid hydrolases from serum.

Juvenile amaurotic idiocy (neuronal ceroid lipofuscinosis) and lymphocyte fingerprint profiles

Lymphocytes from 3 children with a form of juvenile amaurotic idiocy (characterized by retinal blindness, progressive dementia, and extrapyramidal motor disturbance) were studied by electron microscopy. Numerous fingerprint profiles (FP) were found in vacuolated lymphocytes from all 3 patients and an asymptomatic younger sibling of 1 patient who subsequently became symptomatic. We propose that the combination of this clinical picture and vacuolated lymphocytes with FP is sufficiently distinctive for clinical and research purposes until the biochemical defect is discovered. Wider utilization of ultrastructural study of lymphocytes should increase the number of children diagnosed and allow detection of asymptomatic patients.

Atypical GM 1 ganglioside accumulation in a case of juvenile amaurotic idiocy

The brain and liver from a 7-year-old Japanese girl with juvenile amaurotic idiocy were examined neuropathologically and biochemically. Visceromegaly and skeletal abnormalities were absent. Nerve cells in the central nervous system were swollen and contained fine fat granules. Electronmicroscopically, there were large numbers of irregular bodies in the perikarya and these corresponded to the curvilinear and membranous cytoplasmic bodies. Lipid analysis of the brain revealed that GM 1 ganglioside was increased in the parietal and occipital areas, while the frontal lobe showed a normal ganglioside pattern. N-Acetyl neuraminic acid (NANA) content in all areas was not elevated. Determinations of β-galactosidase activity were within normal ranges. The liver had no accumulation of GM 1 ganglioside and showed a normal β-galactosidase activity. These unusual findings in GM 1 gangliosidosis were discussed.

Ultrastructural study of the vacuoles in the peripheral lymphocytes in juvenile amaurotic idiocy

Lymphocytes of the peripheral blood of 31 patients with juvenile amaurotic idiocy (juvenile form of ceroid lipofuscinosis) were examined with the electron microscope. In all cases, intracytoplasmic clear vacuoles were present, containing round hollow, fingerprint and highly electron dense structures. The combination of these structures, not necessarily in one and the same vacuole, was considered to be highly indicative for the diagnosis of juvenile amaurotic idiocy. In addition to these three structures, parallel tubular inclusion bodies, rectilinear profiles and rod-shaped structures were found but in a number of the cases. The parallel tubular inclusion bodies were not regarded as having any diagnostic significance.

Peripheral nerve involvement in Batten-Spielmeyer-Vogt's disease.

Electromyography and sensory and motor nerve conduction were studied in 23 patients with Batten-Spielmeyer-Vogt's disease ("juvenile amaurotic idiocy", cerebral ceroidlipofuscinosis). A slight to moderate slowing of the sensory conduction velocity was found in the median as well as in the sural nerve, more pronounced in the distal than in the proximal segments. The findings are interpreted as evidence of impaired transmission of the peripheral nerves in Batten-Spielmeyer-Vogt's disease.

On the Epidemiology of Juvenile Amaurotic Idiocy in Denmark

Juvenile amaurotic idiocy is an autosomal recessive disease with onset around 6 years of age. Principal symptoms are: blindness; dementia; focal and generalized seizures; cerebellar, striatic, and pyramidal deficits; and psychosis. The course is progressive, common duration 10-20 years. Epidemiological studies are very few, but important work has been done by Sjöstrand and Rayner in Sweden.The preliminary results of the present study indicate a rather higher incidence of the disease in Denmark. It is furthermore demonstrated that there is no evidence of consanguinity between parents, and that the disease is geographically evenly distributed. These findings are in contrast with earlier epidemiological investigations.

A clinical and psychological investigation into juvenile amaurotic idiocy in Denmark.

A clinical and psychological investigation into juvenile amaurotic idiocy in Denmark.

The significance of cytoplasmic inclusions in late infantile and juvenile amaurotic idiocy. An ultrastructural study.

The electron microscopic findings of cerebral biopsies from two siblings with late infantile-juvenile amaurotic idiocy are presented. One patient had a mixture of “fingerprint” and multilamellar inclusions, often in the same cytosome. The second patient had only “fingerprint” inclusions. Electron microscopic findings in autopsied tissues from two other cases of late infantile-juvenile amaurotic idiocy with multilamellar cytosomes are also presented. Evolution of the multilamellar cytosomes into lipofuscin was not observed. We concluded that cases of late infantile-juvenile amaurotic idiocy with multilamellar and “fingerprint” inclusions should be distinguished from cases with lipofuscin.

Lipid-peroxidation in Spielmeyer-Vogt's disease.

The composition of fatty acids in erythrocytes and their sensitivity to H2O2 were estimated in 10 normals and in 5 patients suffering from juvenile amaurotic idiocy or Spielmeyer-Vogt's disease. Serum fatty acid composition, total polyunsaturated fatty acids, total esterified fatty acids and lipid-peroxides were estimated in blood obtained from 20 normals, 5 patients, and 5 neurological controls. Erythrocyte fatty acids and their peroxidation sensitivity showed no difference between patients and normals. The neurological controls and the patients showed lower serum linoleic acid values as compared with the normals and more variation in the fatty acids of longer chain length. In the patients a negative relationship between the linoleic acid values and the clinical phase of the disease was observed. The findings are discussed with regard to previous studies.

Urinary excretion of amino acids in juvenile amaurotic idiocy

Urinary excretion of amino acids was measured with an automated column chromatographic method in 18 patients with juvenile amaurotic familial idiocy. The earlier described imidazoluria in this kind of patient could not be verified in this study. Possible reasons for the results are discussed. It is concluded that imidazoluria, when existing, may be a secondary phenomenon not directly related to the primary defect.

Specific involvement of muscle, nerve, and skin in late infantile and juvenile amaurotic idiocy.

Specific involvement of muscle, nerve, and skin in late infantile and juvenile amaurotic idiocy.

Ultrastructural studies in late-onset amauroticidiocy: Lymphocyte inclusions as a diagnostic marker

Light and electron microscopic studies have been carried out on brain and white bloodcells from a patient with juvenile amaurotic idiocy. A variety of lipid inclusions, including both "multilamellar cytosomes" and "fingerprint" inclusions, were present in the brain, suggesting that these 2 morphologic types of inclusions may not always define separate metabolic disorders. In the lymphocytes, ultrastructurally striking lamellar cytoplasmic inclusions were found. Such inclusions have not previously been described in this disorder. The demonstration of these inclusions by electron microscopy may prove to be a distinctive and relatively simple diagnostic marker of the disease, or at least of the "type" of late-onset amaurotic idiocy present in this patient.

Cytoplasmic inclusions in juvenile amaurotic idiocy

Several forms of neuronal and glial cytoplasmic bodies have been observed with the electron microscope in cerebral biopsies from patients with juvenile amaurotic idiocy. In this study, another cytoplasmic inclusion, with contents resembling fingerprint markings,⁸ has been found in neurons and astrocytes in 4 cases of juvenile amaurotic idiocy. These studie suggest that juvenile amaurotic idiocy is the manifestation of several distinct cellular disorders.

Ultrastructure of rectal biopsies in juvenile amaurotic idiocy.

Ultrastructure of rectal biopsies in juvenile amaurotic idiocy.

Lysosomal enzymes in juvenile amaurotic idiocy.

SummaryThe activity of several acid hydrolases was measured in tissues and plasma from patients with juvenile amaurotic idiocy (JAI). Increased activities were found for β‐galactosidase, β‐glucuronidase, β‐acetylglucosaminidase, acid phosphatase and α‐fucosidase. No significant changes were found for α‐mannosidase, except a slight decrease in plasma. The results show similarities to the findings in gargoylism and a new disease, resembling Hurler's syndrome. These two diseases are supposed to be caused by primary lysosomal enzyme defects. It is suggested that the role of the lysosomes in the pathogenesis of JAI should be studied in more detail.

Early childhood cerebral lipidosis with prominent myoclonus. Ultrastructural and histochemical studies of a cerebral biopsy.

DISTINCTIVE membranous cytoplasmic lipid inclusions have been demonstrated in ultrastructural studies of patients with infantile amaurotic idiocy (Tay-Sachs disease). 1-3 This suggests that other lipidoses may also have characteristic morphological lipid configurations which would aid in their differentiation. The classification of cerebral lipidoses in older children is confused. 4 These have generally been divided into late infantile amaurotic idiocy (Bielschowsky-Jansky disease) and juvenile amaurotic idiocy (Batten-Spielmeyer-Vogt disease). Whether these lipidoses are separate entities or whether they are manifestations at different ages of a similar disease is disputed. Attempts have been made to correlate the ultrastructure of the lipid with the clinical syndromes termed late infantile amaurotic idiocy, 5,6 systemic late infantile lipidosis, 7 juvenile amaurotic idiocy, 8,9 and juvenile lipidosis. 10 Due to varying terminology, similar lipid inclusions are often described under different clinical names. No consistent pattern on electron microscopic examination has emerged. This report presents histochemical and