Free sialic acid storage (Salla) disease in Sweden

Erikson, Anders; Aula, Nina; Aula, Pertti; Je, Månsson

doi:10.1111/j.1651-2227.2002.tb02828.x

Cited by 20 publications

(6 citation statements)

References 10 publications

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“…It has been well documented that patients with disorders of free sialic acid storage (infantile sialic acid storage diseases and Salla disease) have developmental delay with marked cognitive and motor impairment and frequently have severe seizures (Erikson et al, 2002;Wreden et al, 2005). Although these clinical observations demonstrate the importance of sialic acids in brain excitability, the underlying mechanisms remain unknown.…”

Section: Discussionmentioning

confidence: 94%

Role of Extracellular Sialic Acid in Regulation of Neuronal and Network Excitability in the Rat Hippocampus

Isaev¹,

Isaeva²,

Shatskih³

et al. 2007

J. Neurosci.

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The extracellular membrane surface contains a substantial amount of negatively charged sialic acid residues. Some of the sialic acids are located close to the pore of voltage-gated channel, substantially influencing their gating properties. However, the role of sialylation of the extracellular membrane in modulation of neuronal and network activity remains primarily unknown. The level of sialylation is controlled by neuraminidase (NEU), the key enzyme that cleaves sialic acids. Here we show that NEU treatment causes a large depolarizing shift of voltage-gated sodium channel activation/inactivation and action potential (AP) threshold without any change in the resting membrane potential of hippocampal CA3 pyramidal neurons. Cleavage of sialic acids by NEU also reduced sensitivity of sodium channel gating and AP threshold to extracellular calcium. At the network level, exogenous NEU exerted powerful anticonvulsive action both in vitro and in acute and chronic in vivo models of epilepsy. In contrast, a NEU blocker (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid) dramatically reduced seizure threshold and aggravated hippocampal seizures. Thus, sialylation appears to be a powerful mechanism to control neuronal and network excitability. We propose that decreasing the amount of extracellular sialic acid residues can be a useful approach to reduce neuronal excitability and serve as a novel therapeutic approach in the treatment of seizures.

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Section: Discussionmentioning

confidence: 94%

Role of Extracellular Sialic Acid in Regulation of Neuronal and Network Excitability in the Rat Hippocampus

Isaev¹,

Isaeva²,

Shatskih³

et al. 2007

J. Neurosci.

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“…Children with both syndromes have severe developmental delay, failure to gain weight, and failure in growth, with a fatal course in early childhood (Lemyre et al, ). These are very rare diseases; a few dozen ISSD patients have been diagnosed worldwide, and Salla disease occurs only in Finland and Sweden (Erikson et al, ).…”

Section: Atomic Structures and Characteristic Of P0 (Bovine) Glycansmentioning

confidence: 99%

Glycans of myelin proteins

Sędzik

Jastrzebski

Grandis

2014

J of Neuroscience Research

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Human P0 is the main myelin glycoprotein of the peripheral nervous system. It can bind six different glycans, all linked to Asn(93) , the unique glycosylation site. Other myelin glycoproteins, also with a single glycosylation site (PMP22 at Asn(36) , MOG at Asn(31) ), bind only one glycan. The MAG has 10 glycosylation sites; the glycoprotein OMgp has 11 glycosylation sites. Aside from P0, no comprehensive data are available on other myelin glycoproteins. Here we review and analyze all published data on the physicochemical structure of the glycans linked to P0, PMP22, MOG, and MAG. Most data concern bovine P0, whose glycan moieties have an MW ranging from 1,294.56 Da (GP3) to 2,279.94 Da (GP5). The pI of glycosylated P0 protein varies from pH 9.32 to 9.46. The most charged glycan is MS2 containing three sulfate groups and one glucuronic acid; whereas the least charged one is the BA2 residue. All glycans contain one fucose and one galactose. The most mannose rich are the glycans MS2 and GP4, each of them has four mannoses; OPPE1 contains five N-acetylglucosamines and one sulfated glucuronic acid; GP4 contains one sialic acid. Furthermore, human P0 variants causing both gain and loss of glycosylation have been described and cause peripheral neuropathies with variable clinical severity. In particular, the substitution T(95) →M is a very common in Europe and is associated with a late-onset axonal neuropathy. Although peripheral myelin is made up largely of glycoproteins, mutations altering glycosylation have been described only in P0. This attractive avenue of research requires further study.

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“…The compound heterozygote patients have more severe clinical manifestations than the Arg39Cys homozygotes. More than 30 cases of SD have been detected in Sweden, where most patients are homozygous for the Finnish founder mutation (Erikson et al, 2002). Some cases have also been reported in other countries.…”

Section: Introductionmentioning

confidence: 99%

Prenatal diagnosis of free sialic acid storage disorders (SASD)

Aula

2006

Prenatal Diagnosis

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Free sialic acid storage disorders, Salla disease (SD) and Infantile sialic acid storage disease (ISSD), are lysosomal storage diseases due to impaired function of a sialic acid transporter, sialin, at the lysosomal membrane. Several mutations of the sialin gene, SLC17A5, are known, leading either to the severe neonatal/infantile disease or to the milder, adult-type developmental disorder, Salla disease. Free sialic acid accumulation in lysosomes causes increased tissue concentration and consequently elevated urinary excretion. Prenatal diagnosis of SASD is possible either by determination of free sialic acid concentration or by mutation analysis of the SLC17A5 gene in fetal specimen, in chorionic villus biopsy particularly. Both techniques have been successfully applied in several cases, sialic acid assay more often in ISSD cases but mutation analysis preferentially in SD. Sialic acid assay of amniotic fluid supernatant or cultured amniotic fluid cells may give erroneous results and should not be used for prenatal diagnosis of these disorders. The present comments are mainly based on our experience of prenatal diagnosis of SD in Finnish families. A founder mutation in SLC17A5 gene, 115C-> T, represents 95% of the disease alleles in the Finnish SD patients, which provides a unique possibility to apply mutation analysis. Therefore, molecular studies have successfully been used in 17 families since the identification of the gene and the characterization of the SD mutations. Earlier, eight prenatal studies were performed by measuring the free sialic acid concentration in chorionic villus samples.

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Free sialic acid storage (Salla) disease in Sweden

Cited by 20 publications

References 10 publications

Role of Extracellular Sialic Acid in Regulation of Neuronal and Network Excitability in the Rat Hippocampus

Role of Extracellular Sialic Acid in Regulation of Neuronal and Network Excitability in the Rat Hippocampus

Glycans of myelin proteins

Prenatal diagnosis of free sialic acid storage disorders (SASD)

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