Salla disease

Renlund, Martin; Aula, Pertti; Raivio, Kari O.; Autio, S.; Sainio, Kimmlo; Rapola, Juhani; Koskela, Sirkka-Liisa

doi:10.1212/wnl.33.1.57

Cited by 75 publications

(48 citation statements)

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“…The skin biopsy pointed to a lysosomal storage disease, speciWcally one involving the storage of small molecules like sialic acid or an oligosaccharide [20]. The morphological Wndings in our patient were identical to those observed in skin and in conjunctiva of sialic acid storage disease patients [6,21]. However, a skin biopsy does not always show abnormal Wndings in lysosomal storage diseases, including those involving free sialic acid [18].…”

Section: Discussionsupporting

confidence: 67%

“…Individuals with symptoms of moderate severity are considered to have "intermediate severe Salla disease." There is a correlation between the phenotypes of these three groups of patients and their genetic mutations in SLC17A5, the gene that codes for the lysosomal sialic acid transporter, sialin [3][4][5][6][7][8][9]. The diVerential diagnosis of free sialic acid storage also includes sialuria, due to defective feedback inhibition of UDP-GlcNAc-2-epimerase by CMP-sialic acid in the sialic acid synthetic pathway [10].…”

Section: Introductionmentioning

confidence: 99%

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Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity

Kleta¹,

Morse²,

Orvisky³

et al. 2004

Molecular Genetics and Metabolism

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The allelic autosomal recessive lysosomal storage disorders Salla disease and infantile free sialic acid storage disease (ISSD) result from mutations in SLC17A5. This gene codes for sialin, a lysosomal membrane protein that transports the charged sugar, N-acetylneuraminic acid (sialic acid), out of lysosomes. ISSD has a severe phenotype with infantile onset, while the Finnish variant, Salla disease, has a milder phenotype with later onset. Both disorders cause developmental delay, and ISSD is generally fatal in early childhood. We describe a 30-month old non-Finnish, Caucasian child with global developmental delay of postnatal onset, language, and motor skills stagnant at a 3-4 month level, hypotonia, and mild but progressive coarsening of facial features. Urinary excretion of free sialic acid was elevated 4.5 times above control. EM of a skin biopsy revealed enlarged secondary lysosomes consistent with oligosaccharide storage. Free sialic acid in Wbroblasts was 3.8 § 0.9 nmol/mg protein (concurrent normal controls, 0.5 § 0.1); diVerential centrifugation indicated a lysosomal location. Genomic analysis revealed compound heterozygosity for two new SLC17A5 mutations. This child's clinical manifestations of a lysosomal free sialic acid storage disease are consistent with her sialin mutations and biochemical Wndings. The diVerential diagnosis of postnatal developmental delay should include free sialic acid storage disorders such as ISSD and Salla disease. Published by Elsevier Inc.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity

Kleta¹,

Morse²,

Orvisky³

et al. 2004

Molecular Genetics and Metabolism

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“…The main clinical features are early onset psychomotor retardation and ataxia, slow progression of the disease, and almost normal life expectancy (1,2 In Salla patients, the concentration offree sialic acid in tissues is 15-30-fold increased (3) and large amounts ofthis compound are excreted in the urine (4). Electron microscopic and histochemical studies have indicated that sialic acid accumulates in the lysosome (1,2,5).…”

Section: Introductionmentioning

confidence: 99%

“…Electron microscopic and histochemical studies have indicated that sialic acid accumulates in the lysosome (1,2,5). Biochemical studies on liver tissue and cultured fibroblasts have not revealed defects in the activities of the main cellular enzymes involved in sialic acid metabolism (3).…”

Section: Introductionmentioning

confidence: 99%

Studies on the defect underlying the lysosomal storage of sialic acid in Salla disease. Lysosomal accumulation of sialic acid formed from N-acetyl-mannosamine or derived from low density lipoprotein in cultured mutant fibroblasts.

Renlund¹,

Kovanen²,

Raivio³

et al. 1986

J. Clin. Invest.

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IntroductionSalla disease is a lysosomal storage disorder characterized by mental retardation and disturbed sialic acid metabolism. To study the metabolism of extracellular sialic acid, lowdensity lipoprotein (LDL) was labeled in the sialic acid moiety (periodate-NaB3H4) or in the protein moiety (125I). Binding, interialization, lysosomal degradation, and exit of products of protein catabolism were similar in normal and mutant fibroblasts. Upon incubation with LDL labeled in the sialic acid moiety, mutant cells accumulated 2-3 times more free sialic acid radioactivity than normal fibroblasts, mostly in the lysosomal fraction. After a 24-h chase incubation, radioactivity in free sialic acid decreased by 70-80% in normal but only by 10-30% in mutant cells. In mutant fibroblasts, 40% of the radioactivity remained in lysosomes, whereas no labeled free sialic acid was detected in lysosomes from normal fibroblasts.We conclude that in Salla disease, fibroblast endogenous synthesis of sialic acid and lysosomal cleavage of exogenous glycoconjugates is normal, but free sialic acid cannot leave the lysosome. These findings suggest that the basic defect in Salla disease is deficient transport of free sialic acid through the lysosomal membrane.

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“…N-acetyl- (4,5,6,7,8,9-14C)-neuraminic acid (200 mCi/mmol) was from Amersham (Buckinghamshire, England). Unlabeled NANA and ManNAc were obtained from Sigma (Munich, FRG) and digitonin from Merck (Darmstadt, FRG).…”

mentioning

confidence: 99%

Infantile Sialic Acid Storage Disease: The Fate of Biosynthetically Labeled N-Acetyl-(3H)-Neuraminic Acid in Cultured Human Fibroblasts

1986

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Salla disease

Cited by 75 publications

References 0 publications

Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity

Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity

Studies on the defect underlying the lysosomal storage of sialic acid in Salla disease. Lysosomal accumulation of sialic acid formed from N-acetyl-mannosamine or derived from low density lipoprotein in cultured mutant fibroblasts.

Infantile Sialic Acid Storage Disease: The Fate of Biosynthetically Labeled N-Acetyl-(3H)-Neuraminic Acid in Cultured Human Fibroblasts

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