Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the clinical course and EEG evolution of an extreme low birth weight preterm neonate with an uncommon type of glycine encephalopathy. The patient presented with myoclonic jerks, apnea and encephalopathy three months after birth without satisfactory therapeutic response. During the first days of clinical symptoms the patient presented a paroxystic burst-attenuation EEG pattern which progressively evolved into an established typical burst-suppression pattern within a few days. West syndrome occurred four weeks later and the patient died at seven months of extra-uterine life due to a serious respiratory infection with cardio-respiratory arrest. Genetic analysis showed a non-previously described mutation affecting a consensus splice site (IVS2-1G > C 3) in the AMT gene encoding the T protein of the glycine cleavage system.
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PMID:Atypical glycine encephalopathy in an extremely low birth weight infant: description of a new mutation and clinical and electroencephalographic analysis. 1929 30

Glycine encephalopathy (GE), also known as non-ketotic hyperglycinemia, is a life-threatening metabolic disease caused by inherited deficiency of the glycine cleavage system (GCS). GE is characterized by accumulation of a large amount of glycine in serum and cerebrospinal fluids. In typical cases with GE, coma, profound hypotonia, and intractable seizures develop within several days of life. Patients with atypical symptoms may have delayed or missed diagnosis because of non-specific symptoms. It is sometimes problematic to confirm the diagnosis of GE since it requires either invasive liver biopsy for measurement of GCS activity or exhaustive mutational screening of three GCS genes, GLDC, AMT, and GCSH. We herein describe two novel laboratory tests for diagnosis of GE, [1-(13)C]glycine breath test and the multiplex ligation-dependent probe amplification (MLPA) for detection of large deletions in GLDC. The [1-(13)C]glycine breath test has been developed for noninvasive enzymatic diagnosis of GE. Because the GCS generates CO(2) by degradation of glycine, the GCS activity could be evaluated in vivo by measurement of exhaled (13)CO(2) after administration of a stable isotope, [1-(13)C]glycine. The MLPA has been developed for improvement in mutation detection rate in GE: Deletions involving multiple GDLC exons are prevalent among GE patients, but cannot be detected by the exon-sequencing analysis. Two novel diagnosis methods would facilitate diagnosis of hyperglycinemic patients as having GE.
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PMID:Two novel laboratory tests facilitating diagnosis of glycine encephalopathy (nonketotic hyperglycinemia). 2147 Aug 5

Patients with nonketotic hyperglycinemia and deficient glycine cleavage enzyme activity, but without mutations in AMT, GLDC or GCSH, the genes encoding its constituent proteins, constitute a clinical group which we call 'variant nonketotic hyperglycinemia'. We hypothesize that in some patients the aetiology involves genetic mutations that result in a deficiency of the cofactor lipoate, and sequenced genes involved in lipoate synthesis and iron-sulphur cluster biogenesis. Of 11 individuals identified with variant nonketotic hyperglycinemia, we were able to determine the genetic aetiology in eight patients and delineate the clinical and biochemical phenotypes. Mutations were identified in the genes for lipoate synthase (LIAS), BolA type 3 (BOLA3), and a novel gene glutaredoxin 5 (GLRX5). Patients with GLRX5-associated variant nonketotic hyperglycinemia had normal development with childhood-onset spastic paraplegia, spinal lesion, and optic atrophy. Clinical features of BOLA3-associated variant nonketotic hyperglycinemia include severe neurodegeneration after a period of normal development. Additional features include leukodystrophy, cardiomyopathy and optic atrophy. Patients with lipoate synthase-deficient variant nonketotic hyperglycinemia varied in severity from mild static encephalopathy to Leigh disease and cortical involvement. All patients had high serum and borderline elevated cerebrospinal fluid glycine and cerebrospinal fluid:plasma glycine ratio, and deficient glycine cleavage enzyme activity. They had low pyruvate dehydrogenase enzyme activity but most did not have lactic acidosis. Patients were deficient in lipoylation of mitochondrial proteins. There were minimal and inconsistent changes in cellular iron handling, and respiratory chain activity was unaffected. Identified mutations were phylogenetically conserved, and transfection with native genes corrected the biochemical deficiency proving pathogenicity. Treatments of cells with lipoate and with mitochondrially-targeted lipoate were unsuccessful at correcting the deficiency. The recognition of variant nonketotic hyperglycinemia is important for physicians evaluating patients with abnormalities in glycine as this will affect the genetic causation and genetic counselling, and provide prognostic information on the expected phenotypic course.
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PMID:Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. 2433 90

Glycine cleavage system (GCS) catalyzes the degradation of glycine and disruption of its components encoded by GLDC, AMT and GCSH are the only known causes of glycine encephalopathy, also known as non-ketotic hyperglycinemia (NKH). In this report, we describe a consanguineous family with one child who presented with NKH, but harbored no pathogenic variants in any of the three genes linked to this condition. Whole-exome sequencing revealed a novel homozygous missense variant in exon 9 of SLC6A9 NM_201649.3: c.1219 A>G (p.Ser407Gly) that segregates with the disease within the family. This variant replaces the highly conserved S407 in the ion-binding site of this glycine transporter and is predicted to disrupt its function. In murine model, knockout of Slc6a9 is associated with equivalent phenotype of NKH, namely respiratory distress and hypotonia. This is the first demonstration that mutation of the glycine transporter can be associated with NKH in humans.
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PMID:Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans. 2748 95