Urinary sediment dolichols in the diagnosis of neuronal ceroid‐lipofuscinosis

Wolfe, L. S.; Palo, J.; Santavuori, Pirkko; Andermann, Frédérick; Andermann, Eva; Jacob, Jacob C.; Kolodny, Edwin H.

doi:10.1002/ana.410190308

Cited by 47 publications

(9 citation statements)

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“…Interestingly, there are parallels in the relative content of a-tocopherol and dolichol in human tissues, with both enriched in adrenals, testes, and the pituitary (Machlin 1984; Rupar and Carroll 1978). In neuronal ceroid-lipofuscinoses, dolichols are elevated in urinary sediments and the cerebral cortex (Wolfe et al 1986); however, there are no corresponding data on the presence of a-tocopherol.…”

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confidence: 95%

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Rat liver lysosome membranes are enriched in α-tocopherol

Rupar

Albo²,

Jd³

1992

Biochem. Cell Biol.

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The subcellular distribution of alpha-tocopherol has been studied in rat liver. Lysosomal membranes were found to be considerably enriched in alpha-tocopherol with 6300 pmol/mg membrane protein, whereas mitochondrial membranes and microsomes contained 530 and 200 pmol/mg membrane protein, respectively. The 37-fold higher specific content of alpha-tocopherol in lysosomal membranes relative to homogenate indicates that lysosomes could be a target of cellular pathology in vitamin E deficiency states.

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Section: <mentioning

confidence: 95%

“…The cellular origin of ceroid-lipofuscin is not clear, but neuronal ceroid-lipofuscinoses, a group of inherited metabolic disorders for which the defective gene product is unknown, result in ceroid-lipofuscin accumulation. The disease progression is more similar t o that of a lysosomal rather than a mitochondrial disorder (Wolfe et al 1986). …”

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confidence: 95%

Rat liver lysosome membranes are enriched in α-tocopherol

Rupar

Albo²,

Jd³

1992

Biochem. Cell Biol.

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“…Later, the substance was actually shown to be dolichol [Goebel et al, 19791 and subsequently, Wolfe and Ng Yin Kim [19821 proposed that NCL was caused by a defect in dolichol metabolism. Wolfe et al [1986] further showed that patients with NCL exhibit elevated urinary dolichol levels, as well as increased dolichol storage in brain. A study of dolichol levels indicated that false-negative results were obtained in 7.5%-15% of patients with NCL, while false positives were seen in 8.2-14.3% of patients with other neurological diseases, as well as with 15.4% of normal controls.…”

Section: Dolichols (Polyisoprenols) Wolfe Et Al [19771 Reported Retimentioning

confidence: 92%

Perspective of biochemical research in the neuronal ceroid‐lipofuscinosis

Rider¹,

Dawson

Siakotos

1992

Am. J. Med. Genet.

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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)

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“…Dolichols and dolichol phosphates are elevated in brain and urine in all forms, but this probably represents a secondary effect. Unfortunately, the sensitivity and specificity of urinary dolichols are insufficient to be used as a definitive diagnostic test (Wolfe et al, 1983(Wolfe et al, , 1986. At present, diagnosis requires the electron microscopic demonstration of characteristic inclusions.…”

Section: Neuronal Ceroid Lipofuscinosesmentioning

confidence: 99%

Progressive Myoclonus Epilepsies: Clinical and Genetic Aspects

et al. 1993

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The progressive myoclonus epilepsies (PMEs) are a group of rare genetic disorders previously shrouded in nosological confusion. Recent advances have clarified the features of these disorders and provided a rational approach to diagnosis. The major causes of PME are now known to be Unverricht—Lundborg disease, myoclonus epilepsy ragged‐red fiber (MERRF) syndrome, Lafora disease, neuronal ceroid lipofuscinoses, and sialidoses. Over the past 3 years, a series of molecular genetic findings have further refined the understanding of the PMEs. The specific mutation responsible for many cases of MERRF has been identified, and the genes for Unverricht—Lundborg disease and for juvenile neuronal ceroid lipofuscinosis have been linked to chromosomes 21 and 16, respectively. Although the PMEs are among the rarest of the inherited epilepsies, because of molecular genetic discoveries they may soon be the best understood at the neurobiologic level.

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Urinary sediment dolichols in the diagnosis of neuronal ceroid‐lipofuscinosis

Cited by 47 publications

References 11 publications

Rat liver lysosome membranes are enriched in α-tocopherol

Rat liver lysosome membranes are enriched in α-tocopherol

Perspective of biochemical research in the neuronal ceroid‐lipofuscinosis

Progressive Myoclonus Epilepsies: Clinical and Genetic Aspects

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