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Clinical Neuropharmacology 2006Sarcosinemia is a relatively rare autosomal recessive disorder that has a varied phenotypic presentation; rarely, it is associated with neurodevelopmental and... (Review)
Review
Sarcosinemia is a relatively rare autosomal recessive disorder that has a varied phenotypic presentation; rarely, it is associated with neurodevelopmental and neurological abnormalities. Sarcosine is a key intermediate in 1-carbon metabolism, and its elevation in blood and urine could reflect a deficient pool size of activated 1-carbon units. Sarcosine is also an inhibitor of an important glycine transporter in brain and is under clinical investigation as a glycinergic intervention for conditions with presumed N-methyl-d-aspartate (NMDA) receptor hypofunction, such as schizophrenia. Preclinical research with a mouse model that is used to study pharmacological modulation of endogenous NMDA receptor-mediated tone may clarify, at least in some instances, varied phenotypic presentations of sarcosinemia that are often clinically benign. Sarcosine's effectiveness as a glycinergic agonist intervention for NMDA receptor hypofunction depends on an interaction between genetic background and a stressful environmental insult. Thus, neurodevelopmental and neurological abnormalities may manifest rarely in sarcosinemia in the context of relatively unique genetic factors and fetal insult or stress.
Topics: Amino Acid Metabolism, Inborn Errors; Brain; Central Nervous System Diseases; Glycine; Glycine Plasma Membrane Transport Proteins; Humans; Receptors, N-Methyl-D-Aspartate; Sarcosine
PubMed: 17095900
DOI: 10.1097/01.WNF.0000236767.46526.1F -
Ryoikibetsu Shokogun Shirizu 1998
Review
Topics: Amino Acid Metabolism, Inborn Errors; Diagnosis, Differential; Folic Acid Deficiency; Humans; Sarcosine; Vitamin B 12 Deficiency
PubMed: 9590031
DOI: No ID Found -
Metabolic Brain Disease Apr 2016In the present study, we developed an acute chemically induced model of sarcosinemia in Wistar rats. Wistar rats of 7, 14 and 21 postpartum days received sarcosine...
In the present study, we developed an acute chemically induced model of sarcosinemia in Wistar rats. Wistar rats of 7, 14 and 21 postpartum days received sarcosine intraperitoneally in doses of 0.5 mmol/Kg of body weight three time a day at intervals of 3 h. Control animals received saline solution (NaCl 0.85 g%) in the same volume (10 mL/Kg of body weight). The animals were killed after 30 min, 1, 2, 3 or 6 h after the last injection and the brain and the blood were collected for sarcosine measurement. The results showed that plasma and brain sarcosine concentrations achieved levels three to four times higher than the normal levels and decreased in a time-dependent way, achieving normal levels after 6 hours. Considering that experimental animal models are useful to investigate the pathophysiology of human disorders, our model of sarcosinemia may be useful for the research of the mechanisms of neurological dysfunction caused by high tissue sarcosine levels.
Topics: Acute Disease; Amino Acid Metabolism, Inborn Errors; Animals; Animals, Newborn; Brain; Disease Models, Animal; Mitochondrial Diseases; Rats, Wistar; Sarcosine; Sarcosine Dehydrogenase
PubMed: 26563127
DOI: 10.1007/s11011-015-9759-9 -
Human Genetics Nov 2012Sarcosinemia is an autosomal recessive metabolic trait manifested by relatively high concentrations of sarcosine in blood and urine. Sarcosine is a key intermediate in...
Sarcosinemia is an autosomal recessive metabolic trait manifested by relatively high concentrations of sarcosine in blood and urine. Sarcosine is a key intermediate in 1-carbon metabolism and under normal circumstances is converted to glycine by the enzyme sarcosine dehydrogenase. We encountered six families from two different descents (French and Arab), each with at least one individual with elevated levels of sarcosine in blood and urine. Using the "candidate gene approach" we sequenced the gene encoding sarcosine dehydrogenase (SARDH), which plays an important role in the conversion of sarcosine to glycine, and found four different mutations (P287L, V71F, R723X, R514X) in three patients. In an additional patient, we found a uniparental disomy in the region of SARDH gene. In two other patients, we did not find any mutations in this gene. We have shown for the first time that mutations in the SARDH gene are associated with sarcosinemia. In addition, our results indicate that other genes are most probably involved in the pathogenesis of this condition.
Topics: Amino Acid Metabolism, Inborn Errors; DNA; DNA Primers; Female; Humans; Male; Mitochondrial Diseases; Mutation; Pedigree; Phenotype; Polymerase Chain Reaction; Sarcosine; Sarcosine Dehydrogenase
PubMed: 22825317
DOI: 10.1007/s00439-012-1207-x -
The Journal of Pediatrics Nov 1970
Topics: Amino Acid Metabolism, Inborn Errors; Child, Preschool; Culture Techniques; Fibroblasts; Glycine; Humans; Intellectual Disability; Leukocytes; Male; Oxidoreductases; Sarcosine; Skin
PubMed: 5504071
DOI: 10.1016/s0022-3476(70)80239-6 -
JIMD Reports 2013Sarcosinemia is a rare inborn error of metabolism that is characterised by an increased level of sarcosine (N-methylglycine) in the plasma and urine. The enzymatic block...
Sarcosinemia is a rare inborn error of metabolism that is characterised by an increased level of sarcosine (N-methylglycine) in the plasma and urine. The enzymatic block results from a deficiency of sarcosine dehydrogenase (SarDH), a liver mitochondrial matrix enzyme that converts sarcosine into glycine. Although this condition may remain inapparent until later life, it has been reported in rare cases to lead to neurodevelopmental disability. A 19-year-old male with sarcosinemia presented with dystonia, developmental delay and cognitive impairment. Magnetic resonance imaging revealed vermian hypotrophy. A 2-year pharmacological treatment with memantine was negative on the clinical signs. In this case, it was concluded that the metabolic block leading to sarcosinemia was responsible of a pathologic condition with mental deficiency and complex neurological signs. A maternal isodisomy discovered in the vicinity of SarDH gene could contribute to this pathology. Deficit of SarDH may be considered as a differential diagnosis of growth failure during prenatal stages and respiratory failure at birth following a slowly progressive developmental delay.
PubMed: 23430553
DOI: 10.1007/8904_2012_185 -
Proceedings of the National Academy of... Apr 1992A mouse mutant with sarcosinemia was found by screening the progeny of ethylnitrosourea-mutagenized mice for aminoacidurias. Paper chromatography, column chromatography,...
A mouse mutant with sarcosinemia was found by screening the progeny of ethylnitrosourea-mutagenized mice for aminoacidurias. Paper chromatography, column chromatography, and gas chromatography-mass spectrometry identified high levels of sarcosine in the urine of the mutant mice. While sarcosine cannot be detected in the urine of plasma of normal mice, the urinary sarcosine level of 102 +/- 58 mmol per g of creatinine in the mutant mice was at the upper range of the urinary levels (1.5-4.5 mmol of sarcosine per g of creatinine) observed in humans with sarcosinemia. Similarly, the plasma sarcosine level of 785 +/- 153 mumol/liter in the sarcosinemic mice was at the upper range of the plasma sarcosine levels (53-760 mumol/liter) observed in affected humans. Sarcosine dehydrogenase [sarcosine:(acceptor) oxidoreductase (demethylating), EC 1.5.99.1] activity was deficient in sarcosinemic mice. The sarcosinuria phenotype in these mice was inherited as an autosomal recessive trait. This mouse mutant provides a useful genetic model for human sarcosinemia and for development of therapeutic approaches for genetic disease.
Topics: Amino Acid Metabolism, Inborn Errors; Animals; Ethylnitrosourea; Gas Chromatography-Mass Spectrometry; Mice; Mice, Mutant Strains; Mutagenesis; Oxidoreductases, N-Demethylating; Phenotype; Sarcosine; Sarcosine Dehydrogenase
PubMed: 1372986
DOI: 10.1073/pnas.89.7.2644 -
Pediatrics Oct 1984Sarcosinemia has been detected by routine screening of urine for metabolic and transport disorders in Massachusetts. Three infants who had sarcosinemia were detected...
Sarcosinemia has been detected by routine screening of urine for metabolic and transport disorders in Massachusetts. Three infants who had sarcosinemia were detected through the neonatal urine specimen, an observed incidence of 1:350,000. A fourth child had sarcosinemia detected through family screening after his brother was found to have Hartnup disease by neonatal urine screening. These four children with sarcosinemia have plasma sarcosine concentrations ranging from 80 to 603 mumol/L and urine sarcosine from 2.1 to 9.4 mumol/mg of creatinine, findings similar to those reported for persons with sarcosinemia. No treatment has been given. At 3.8 to 15 years of age, the children had normal findings on physical examination and had no specific illnesses. Their full-scale IQ scores ranged from 89 to 111. The oldest child had a learning and emotional disorder, and one other child was emotionally unstable. It was concluded that sarcosinemia as a specific disorder is probably benign and that the mental retardation and dysmorphic features described in some affected persons are likely coincidental with the biochemical defect. The emotional disturbances that were encountered in two children are also probably coincidental but need further attention in this disorder.
Topics: Adolescent; Affective Symptoms; Amino Acid Metabolism, Inborn Errors; Child, Preschool; Female; Humans; Intelligence; Male; Mass Screening; Massachusetts; Sarcosine
PubMed: 6207480
DOI: No ID Found -
Biomarkers : Biochemical Indicators of... Jul 2019The quantitative determination of sarcosine is of great importance in clinical chemistry, food and fermentation industries. Elevated sarcosine levels are associated with... (Review)
Review
The quantitative determination of sarcosine is of great importance in clinical chemistry, food and fermentation industries. Elevated sarcosine levels are associated with Alzheimer, dementia, prostate cancer, colorectal cancer, stomach cancer and sarcosinemia. This review summarizes the various methods for quantitative analysis of sarcosine with special emphasis on various strategies of biosensors and their analytical performance. The current bio sensing methods have overcome the drawbacks of conventional methods. Sarcosine biosensors work optimally at pH 7.0 to 8.0 in the linear range of 0.1 to 100 μM within 2 to 17 s and between 25 and 37 °C, within a limit of detection (LOD) between 0.008 and 500 mM. The formulated biosensors can be reused within a stability period of 3-180 days. Future research could be focused to modify existing sarcosine biosensors, leading to simple, reliable, and economical sensors ideally suited for point-of-care treatment. Clinical significance Elevated sarcosine levels are associated with prostate and colorectal cancer, Alzheimer, dementia, stomach cancer and sarcosinemia. Quantitative determination of sarcosine is of great importance in clinical chemistry as well as food and fermentation industries. Attempts made in development of sarcosine biosensors have been reviewed with their advantages and disadvantages, so that scientist and clinicians can improvise the methods of developing more potent sarcosine biosensor applicable in multitudinous fields. This is the first comprehensive review which compares the various immobilization methods, sensing principles, strategies used in biosensors and their analytical performance in detail.
Topics: Alzheimer Disease; Amino Acid Metabolism, Inborn Errors; Biomarkers; Biosensing Techniques; Colorectal Neoplasms; Humans; Male; Mitochondrial Diseases; Prostatic Neoplasms; Sarcosine; Sarcosine Dehydrogenase; Stomach Neoplasms
PubMed: 31050554
DOI: 10.1080/1354750X.2019.1615124 -
Genomics Aug 1999Sarcosine dehydrogenase is a liver mitochondrial matrix flavoenzyme that is defective in patients with sarcosinemia, a rare autosomal metabolic defect characterized by...
Sarcosine dehydrogenase is a liver mitochondrial matrix flavoenzyme that is defective in patients with sarcosinemia, a rare autosomal metabolic defect characterized by elevated levels of sarcosine in blood and urine. Some patients also exhibit mental retardation and growth failure. A full-length cDNA for human sarcosine dehydrogenase was isolated from an adult liver cDNA library. The first 22 residues in the deduced amino acid sequence exhibit features expected for a mitochondrial targeting sequence. The predicted mass of the mature human liver sarcosine dehydrogenase (99,505 Da) is in good agreement with that observed for rat liver sarcosine dehydrogenase ( approximately 100,000 Da). Human sarcosine dehydrogenase exhibits 89% identity with rat liver sarcosine dehydrogenase and strong homology ( approximately 35% identity) with rat liver dimethylglycine dehydrogenase, a sarcosine dehydrogenase-related protein from Rhodobacter capsulatus, and the regulatory subunit from bovine pyruvate dehydrogenase phosphatase. The human sarcosine dehydrogenase gene is at least 75.3 kb long and located on chromosome 9q34. The adult human liver clone is assembled from 21 exons (1-6, 7a, 8a, 9-21). Two smaller cDNA clones, isolated from adult liver and infant brain libraries, were assembled from the same sarcosine dehydrogenase gene by the use of alternate polyadenylation and splice sites. This is the first report of the genomic structure of the sarcosine dehydrogenase gene in any species. The observed chromosomal location is consistent with genetic studies with a mouse model for sarcosinemia that map the mouse gene to a region of mouse chromosome 2 syntenic with human 9q33-q34. The availability of the SDH gene sequence will enable characterization of the genotypes of sarcosinemia patients with different phenotypes.
Topics: Adult; Amino Acid Metabolism, Inborn Errors; Amino Acid Sequence; Animals; Base Sequence; Blotting, Northern; Cattle; Chromosome Mapping; Chromosomes, Human, Pair 9; Cloning, Molecular; DNA, Complementary; Humans; Mice; Molecular Sequence Data; Oxidoreductases, N-Demethylating; Rats; Sarcosine; Sarcosine Dehydrogenase; Sequence Homology, Amino Acid
PubMed: 10444331
DOI: 10.1006/geno.1999.5886