D-Glyceric acidemia 4003388 208151175 2008-04-25T17:41:30Z Arcadian 104523 moved [[Glycine encephalopathy]] to [[D-Glyceric acidemia]]: more common name {{unreferenced|date=February 2008}} {{Infobox_Disease | Name = {{PAGENAME}} | Image = | Caption = | DiseasesDB = 29857 | ICD10 = | ICD9 = | ICDO = | OMIM = 220120 | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = | }} '''Glycine encephalopathy''', also known as '''non-ketotic hyperglycinemia''' or '''NKH''', is an [[autosomal recessive]] [[metabolic disorder]] characterized by abnormally high levels of the amino acid [[glycine]]. Glycine acts as a [[neurotransmitter]], which is a chemical messenger that transmits signals in the brain. Glycine encephalopathy is caused by the shortage of an enzyme that normally breaks down glycine in the body. A lack of this enzyme allows excess glycine to build up in tissues and organs, particularly the brain, leading to serious medical problems. ==Types== ===Classic neonatal form or classic form=== Most patients with GCE have the neonatal phenotype, presenting in the first few days of life with [[lethargy]], [[hypotonia]], and [[myoclonic jerks]],and progressing to [[apnea]], and often to death. Those who regain spontaneous respiration develop intractable seizures and profound [[mental retardation]]. ===Infantile form=== Patients present with [[seizures]] and have various degrees of [[mental retardation]] after a symptom-free interval and seemingly normal development for up to 6 months. ===Mild-episodic form=== Patients present in childhood with mild mental retardation and episodes of [[delirium]], [[chorea]], and [[vertical gaze palsy]] during febrile illness. ===Late-onset form=== Patients present in childhood with progressive [[spastic diplegia]] and [[optic atrophy]], but intellectual function is preserved and [[seizures]] have not been reported ===Atypical form=== Unlike the classic neonatal form of the disorder, atypical or mild glycine [[encephalopathy]] is phenotypically heterogeneous and nonspecific, making diagnosis difficult. The occurrence of an expressive speech deficit and neurologic abnormalities during intercurrent infections as striking features of the milder form of the disease. ===Transient Form=== Transient neonatal hyperglycinemia (TNH) is characterized by elevated [[blood plasma|plasma]] and CSF [[glycine]] levels at birth that are normalized within 2 to 8 weeks. TNH is clinically and biochemically indistinguishable from typical [[nonketotic hyperglycinemia]] at onset. ==Genetics== [[Image:autorecessive.jpg|thumb|right|{{PAGENAME}} has an autosomal recessive pattern of inheritance.]] Mutations in the ''AMT'' and ''GLDC'' genes cause glycine encephalopathy. About 80 percent of cases of glycine encephalopathy result from mutations in the ''GLDC'' gene, while ''AMT'' mutations cause 10 percent to 15 percent of all cases. In a small percentage of affected individuals, the cause of this condition is unknown. The ''AMT'' and ''GLDC'' genes provide instructions for making proteins that work together as part of a larger enzyme complex. This complex, known as [[glycine cleavage enzyme]], is responsible for breaking down glycine into smaller pieces. Mutations in either the ''AMT'' or ''GLDC'' gene prevent the complex from breaking down glycine properly. When glycine cleavage enzyme is defective, excess glycine can build up to toxic levels in the body's organs and tissues. Damage caused by harmful amounts of this molecule in the brain and spinal cord is responsible for the mental retardation, seizures, and breathing difficulties characteristic of glycine encephalopathy. This disorder is inherited in an [[recessive gene|autosomal recessive]] pattern, which means the defective gene is located on an [[autosome]], and two copies of the gene - one from each parent - are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder each carry one copy of the defective gene, but do not show signs or symptoms of the disorder. ==See also== *[[List of amino acid metabolism disorders]] ==External links== *National Library of Medicine. [http://ghr.nlm.nih.gov/condition=glycineencephalopathy?wf=1 Glycine encephalopathy] * NKH-International Family Network [http://www.nkh-network.org] * GeneReview [http://www.geneclinics.org/servlet/access?db=geneclinics&site=gt&id=8888892&key=19Z5K92WsOwuU&gry=&fcn=y&fw=GHf7&filename=/profiles/nkh/index.html] * National Library of Medicine Genetics Home Reference [http://ghr.nlm.nih.gov/condition=glycineencephalopathy] {{Amino acid metabolic pathology}} [[Category:Genetic disorders]] [[Category:Autosomal recessive disorders]] [[Category:Diseases]] [[Category:Inborn errors of metabolism]] [[sr:Хиперглицинемија]]