The Treatment of Isovaleric Acidemia with Glycine Supplement

Naglak, Mary; Salvo, Rino; Madsen, Kevin; Dembure, Philip P.; Elsas, Louis J.

doi:10.1203/00006450-198807000-00004

Cited by 35 publications

(14 citation statements)

References 18 publications

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“…Heresco-Levy et al published their results of glycine administration, 40-90 gr/day in three divided doses for 6 weeks in schizophrenic patients, and only one out of nine patients developed minor side effects (upper abdominal discomfort with nausea and vomiting) that resolved on stopping glycine [93]. D'Souza et al used 100 and 200 mg/kg/day I/V glycine, for 4 days, in a study of its central availability in healthy volunteers, without any adverse effects [95] while Kasai et al used up to 12 gram glycine infusions in a study of its effects on growth hormone secretion [96], and Naglak et al used up to 150, 250 and 600 mg/day glycine in 2 patients with isovaleric academia [97]. …”

Section: Clinical Safetymentioning

confidence: 98%

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

Habib¹,

Hodgson²,

Davidson

2006

CPD

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Glycine is a non-essential amino acid which is cheap, easily available and relatively non-toxic. It is composed of a single carbon attached to an amino and a carboxyl group, with a molecular weight of 75. It is involved in the production of bile, nucleic acids, porphyrins and creatine phosphate. It is part of the normal human diet and is used clinically, as an irrigant solution in urological and gynaecological procedures. Glycine has broad spectrum anti-inflammatory, cytoprotective and immunomodulatory properties whose therapeutic role has largely been un-investigated. Since the demonstration of its cytoprotective effect on hypoxic cultured renal tubule cells, further research has established its mechanism of anti-inflammatory action, which depends on stimulation of glycine sensitive chloride channel receptors on the cell membrane. The mechanism of non-specific cytoprotective effect which is present even in chloride and calcium free media is not clear. However glycine is currently being used experimentally, in human liver transplant recipients and has been shown to be beneficial in animal models of ischemia-reperfusion injury (IRI) in liver and several other organs. This review addresses the properties of glycine, its mechanism of action and its role in modulating IRI with special reference to the liver, with the aim of stimulating translational research into the potential role of glycine as a pharmaceutical agent.

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Section: Clinical Safetymentioning

confidence: 98%

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

Habib¹,

Hodgson²,

Davidson

2006

CPD

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mentioning

confidence: 99%

“…Clinical symptoms include poor feeding, tachypnea, vomiting (2 ), listlessness, lethargy, coma (2,3 ), and dehydration (4 ). Individuals homozygous for this defect are characterized primarily by the excretion of isovalerylglycine (2 ). The metabolic profile may be further complicated by intermediate metabolites such as 3-and 4-hydroxyisovaleric acid (5 ), methylsuccinic acid (6 ), methylfumaric acid (7 ), isovalerylglucuronide (8 ), isovalerylglutamic acid (9 ), Nisovalerylalanine and N-isovalerylsarcosine (10 ), isovalerylcarnitine (11 ), 3-hydroxyisoheptanioc acid (12 ), and alloisoleucine (4 ).…”

mentioning

confidence: 99%

Identification of 19 New Metabolites Induced by Abnormal Amino Acid Conjugation in Isovaleric Acidemia

2005

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analysis (Fig. 1B, lower panel, line 3) confirmed that the result obtained in reaction 3 was a false negative.In the experiments of this study, the RICO was added to the reverse transcription mixture. It is possible to coextract the RICO with the sample RNA to control for the extraction procedure. In this case, however, careful validation is necessary: because of the small size of the RICO, its extraction efficiency might be low or variable depending on the method used. We have noticed these effects when using Qiagen columns for RNA extraction.In summary, we have developed a simple, inexpensive method that allows laboratories to produce their own RNA controls. Sufficient RICO for millions of RT-PCR assays can be produced from a synthetic oligonucleotide in Ͻ5 h with little hands-on time. The RICO technique could be applied to many real-time amplification protocols that use a probe format and an instrument that can perform a melting-point analysis after amplification. Because the method does not require a second, controlspecific probe, it conserves detection channels on the real-time amplification instrument and reduces reagent costs. Because of some difficulty in titrating the amount of RICO needed for reliable detection of partial inhibition of the reverse transcription step, however, a separate probe should still be used to detect the RICO during amplification in quantitative RT-PCR assays.We thank Kathrin Appel, Edina Jelecevic, Naeem Malik, Jeannette Neumann, and Edith Schuhmacher for excellent technical assistance. Isovaleric acidemia (IVA) is an autosomal recessive genetic disorder of the enzyme isovaleryl-CoA dehydrogenase, which is involved in leucine metabolism (1 ). Clinical symptoms include poor feeding, tachypnea, vomiting (2 ), listlessness, lethargy, coma (2, 3 ), and dehydration (4 ). Individuals homozygous for this defect are characterized primarily by the excretion of isovalerylglycine (2 ). The metabolic profile may be further complicated by intermediate metabolites such as 3-and 4-hydroxyisovaleric acid (5 ), methylsuccinic acid (6 ), methylfumaric acid (7 ), isovalerylglucuronide (8 ), isovalerylglutamic acid (9 ), Nisovalerylalanine and N-isovalerylsarcosine (10 ), isovalerylcarnitine (11 ), 3-hydroxyisoheptanioc acid (12 ), and alloisoleucine (4 ). Diagnosis of IVA is based on clinical symptoms and the presence of isovalerylglycine and 3-hydroxyisovaleric acid (13 ), with some of the above-mentioned metabolites also occurring to a greater or lesser extent (4 ). Despite the large number of already identified excreted metabolites, their occurrence still does not entirely explain all of the clinical symptoms experienced by these patients. The statement made in 1982 by Duran et al. (14 ) that "[t]he continuing search for 'new' metabolites may eventually lead to a better understanding of the relationship between the clinical conditions and their biochemical abnormalities" is the motivation for our search for previously unidentified metabolites in IVA. In this study, we analyzed the urine of I...

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“…As episodes of metabolic decompensation are difficult to predict, chronic management with glycine to prevent such episodes has been investigated [16-20]. Several studies support lower doses for maintenance treatment than for acute management, in order to prevent side-effects due to hyperglycinemia [16-18].…”

Section: Resultsmentioning

confidence: 99%

Single amino acid supplementation in aminoacidopathies: a systematic review

Vliet

Derks

Rijn

et al. 2014

Orphanet J Rare Dis

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Aminoacidopathies are a group of rare and diverse disorders, caused by the deficiency of an enzyme or transporter involved in amino acid metabolism. For most aminoacidopathies, dietary management is the mainstay of treatment. Such treatment includes severe natural protein restriction, combined with protein substitution with all amino acids except the amino acids prior to the metabolic block and enriched with the amino acid that has become essential by the enzymatic defect. For some aminoacidopathies, supplementation of one or two amino acids, that have not become essential by the enzymatic defect, has been suggested. This so-called single amino acid supplementation can serve different treatment objectives, but evidence is limited. The aim of the present article is to provide a systematic review on the reasons for applications of single amino acid supplementation in aminoacidopathies treated with natural protein restriction and synthetic amino acid mixtures.

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The Treatment of Isovaleric Acidemia with Glycine Supplement

Cited by 35 publications

References 18 publications

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

Identification of 19 New Metabolites Induced by Abnormal Amino Acid Conjugation in Isovaleric Acidemia

Single amino acid supplementation in aminoacidopathies: a systematic review

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