Nih makes no endorsements of tests or laboratories listed in the gtr. Glycine encephalopathy genetics home reference nih. There is a classical form of nkh and a variant form of nkh. Diagnosis the foundation for nonketotic hyperglycinemia. 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. Glycine encephalopathy nonketotic hyperglycinaemia. Nonketotic hyperglycinemia nkh is a disorder of glycine metabolism due to a molecular defect in the glycine cleavage system gcs1,2. Patients with nonketotic hyperglycinemia generally have intractable seizures that are poorly responsive to anticonvulsant medication. Clinical data, including the clinical manifestations, laboratory tests, imaging studies and other information, of patients with hyperglycemiarelated epilepsy in our department were retrospectively analyzed. Poor outcome for neonataltype nonketotic hyperglycinemia. These two cases may better clarify clinical findings that can be associated with impairment of glycine.
Nkh usually affects infants and children, appearing shortly after birth. In three patients with nonketotic hyperglycinemia, the oral administration of sodium benzoate in dosages. The metabolic lesion of nkh is in the glycine cleavage system gcs, a complex enzyme system with four enzyme components. Jci identification of a common mutation in finnish. Nonketotic hyperglycinemia nkh or glycine encephalopathy is an autosomal recessive disorder characterized by a rapidly progressive course in the neonatal period or early infancy. We hypothesize that in some patients the aetiology involves genetic mutations that result in a. Despite this clinical phenotype and a csfplasma ratio confirming a mild variant, measurement of hepatic glycine cleavage activity and the pprotein component indicated the more severe neonatal variant. Gcs is a complex of four proteins encoded on four different chromosomes. Nonketotic hyperglycinemia nkh is an autosomal recessive disorder of glycine metabolism caused by a defect in the glycine cleavage enzyme complex gcs. Leukoencephalopathy with cysts and hyperglycinemia may. Nonketotic hyperglycinemia glycine cleavage complex deficiency. Pretreatment with paracetamol opposed the hyperglycinemic effect of valproate. Seizures, hypotonia, lethargy, and hiccups are the principal. It is a genetic disorder and is inherited from both parents.
Poor outcome for neonataltype nonketotic hyperglycinemia treated with highdose sodium benzoate and dextromethorphan yinhsiu chien, md, chiachi hsu, md, aichu huang, ms, shiping chou, mr, frankli lu, md, wangtso lee, md, phd, and wuhliang hwu, md, phd. In the second to fifth years of life, multifocal epileptiform discharges. Nonketotic hyperglycinemia nkh is a rare autosomal recessive inborn error of glycine metabolism caused by a defect in the glycine cleavage system. Nonketotic hyperglycinemia nkh due to biallelic pathogenic variants in one of the two genes gldc and amt known to encode the components of the glycine cleavage enzyme system or possibly in a third gene gcsh should be suspected in individuals with the following clinical, laboratory, and neuroimaging findings. Glycine encephalopathy, also termed nonketotic hyperglycinemia nkh, is an autosomal recessive disorder of the catabolism of glycine to carbon dioxide and ammonia van hove et al. The eeg changed to hypsarrhythmia during early or midinfancy. A female infant with neonatal hypotonia and lethargy was found to have nonketotic hyperglycinemia. C r o g nonketotic hyperglycinemia clinical features help list of clinical features of the conditionphenotype displayed from sources such as the human phenotype ontology hpo and omim. Nonketotic hyperglycinemia was originally named to distinguish it from ketotic hyperglycinemia, which is now known to be propionic acidemia 606054.
Five patients with nonketotic hyperglycinemia had serial eegs and evokedresponse studies. Glycine encephalopathy nonketotic hyperglycinemia has an autosomal recessive pattern of inheritance. Nov 14, 2002 nonketotic hyperglycinemia nkh due to biallelic pathogenic variants in one of the two genes gldc and amt known to encode the components of the glycine cleavage enzyme system or possibly in a third gene gcsh should be suspected in individuals with the following clinical, laboratory, and neuroimaging findings. Stats nonketotic hyperglycinemia nonketotic hyperglycinemia. Only a minority of patients develop a milder clinical form. These findings indicate that the primary lesion of hyperglycinemia of nonketotic type is a defect in the. The disorder is caused by deficient activity of the glycine cleavage enzyme complex gcc, which consists of the products of four genes. Most nkh cases are diagnosed during the natal period of life and are fatal if not promptly diagnosed and managed. More detailed information about the symptoms, causes, and treatments of hyperglycinemia is available below symptoms of hyperglycinemia. Hyperglycinemia nonketotic, nonketotic hyperglycinemia, glycine synthase deficiency, nonketotic hyperglycinemia.
Prediction of longterm outcome in glycine encephalopathy. The majority of cases published involved female patients 4. In the neonatal period, the suppressionburst pattern was observed. Nonketotic hyperglycemiarelated epileptic seizures chinese. The disease is caused by defects in the glycine cleavage system, an enzyme responsible for glycine catabolism. The baby was started on sodium benzoate and dextromethorphan. Causes of nonketotic hyperglycinemia an inherited condition like nonketotic hyperglycinemia means the disorder is passed down from a parent 4. Glycine encephalopathy, which is also known as nonketotic hyperglycinemia or nkh, is a genetic disorder characterized by abnormally high levels of a molecule called glycine. In the second to fifth years of life, multifocal epileptiform discharges superimposed on diffuse slow background activity.
The effectiveness of benzoate in the management of. Glycine encephalopathy has an estimated incidence of 1 in 60,000, making it the second most common disorder of amino acid metabolism, after phenylketonuria. Nonketotic hyperglycinemia international family network. In our patient, nonketotic hyperglycinemia was unusual biochemically as the raise of csf glycine was very moderate. Nonketotic hyperglycinemia nkh is a rare genetic disorder caused by a defect in the machinery for the breakdown of the amino acid glycine. Nonketotic hyperglycemiarelated epileptic seizures. If you have problems viewing pdf files, download the latest version of adobe reader.
This molecule is an amino acid, which is a building block of proteins. In three patients with nonketotic hyperglycinemia, the oral administration of sodium benzoate in dosages designed to lower the cerebrospinal fluid concentration of glycine was followed by an abrupt change from frequent major seizures before treatment to no seizures, or only occasional. Chorea and ballismus develops rapidly and can be either unilateral or. Mim238300 an inborn error of glycine metabolism, due to a deficiency of glycine dicarboxylase p protein gcsp, a component of glycine. More detailed information about the symptoms, causes, and treatments of hyperglycinemia is available be. To investigate nonketotic hyperglycemia nkhrelated epileptic clinical features and pathogenesis, and improve the diagnosis and treatment. Because of the huge differences observed in the outcome, researchers from united. These findings indicate that the primary lesion of hyperglycinemia of nonketotic type is a defect in the glyeine cleavage reaction which gives rise to the formation of. Jci identification of a common mutation in finnish patients. Here we present a case of a twodayold child who presented with. Nonketotic hyperglycinemia nkh or glycine encephalopathy is an autosomal recessive disorder characterized by a. Pdf nonketotic hyperglycinemia nkh is an autosomal recessive inborn. Nkh is a rare disorder in many countries, but with a very high incidence in northern finland.
Berry, in averys diseases of the newborn ninth edition, 2012. These two cases may better clarify clinical findings that can be associated with impairment of glycine metabolism. The glycine cleavage system was investigated in the livers and brains of two patients with typical nonketotic hyperglycinemia who died. Nonketotic hyperglycinemia nkh is a rare, genetic, metabolic disorder caused by a defect in the enzyme system that breaks down the amino acid glycine, resulting in an accumulation of glycine in the bodys tissues and fluids. No effective treatment has been consistently reported. The effectiveness of benzoate in the management of seizures. Nonketotic hyperglycinemia is a rare defect of glycine metabolism dulac and rolland, 2006. This means both parents must pass down a copy of the mutated gene in order for the child to get the mutation. Nonketotic hyperglycinemia nkh is an autosomal recessive metabolic disorder caused by the defects in the glycine cleavage system gcs.
Since the distinction is no longer required and clinical confusion between hyperglycinemia and hyperglycemia occurs, a more appropriate name for this disorder is glycine encephalopathy hamosh, 2001. Two novel missense mutations in nonketotic hyperglycinemia. Above all, it is a very complex disease, since it does not affect all the patients the same way. Pdf nonketotic hyperglycinemia case series researchgate. We diagnosed a 22yearold man with psychomotor retardation, rare seizures, hyperglycinemia, and hyperglycinuria as an atypical variant of nonketotic hyperglycinemia nkh. The glycine cleavage system is a mitochondrial enzymatic complex consisting of four distinctive proteins p, h, t, and l. The condition is either fatal or presents with several mental and neurological disability in early life. We describe two cases of early myoclonic encephalopathy, secondary to nonketotic hyperglycinemia, with fatal evolution in the neonatal period. In particular, the ratio of csf to plasma glycine 1% was much lower than the 4% cut off that is recommended for the diagnosis of classical nonketotic hyperglycinemia. There are two types of hyperglycinemia ketotic and nonketotic with different symptoms. There are several forms of the disease, with varying. Patients with the atypical nkh tend to have a lower csfplasma glycine ratio when compared with the.
Inheritance for this particular disorder is autosomal recessive. Nonketotic hyperglycinemia nkh is a metabolic disorder with autosomal recessive inheritance, causing severe, frequently lethal, neurological symptoms in the neonatal period. A rare disorder of amino acid metabolism where glycine and proline are unable to be metabolized properly due to defects in the glycine cleavage system. Nonketotic hyperglycinemia nkh is a genetic disorder characterized by abnormally high levels of glycine, an amino acid that is one of the building blocks of proteins. Nonketotic hyperglycinemia nkh is a disorder of glycine metabolism caused by a defect in the glycine cleavage enzyme system, resulting in high glycine concentrations in urine, plasma, and especially csf and the brain.
Adult nonketotic hyperglycinemia nkh crisis presenting as severe chorea and encephalopathy. Early myoclonic encephalopathy is an epileptic syndrome with different etiologies. Leukoencephalopathy with cysts and hyperglycinemia may result. As his parents we want to contribute to the love and support the nkh community has given and so.
Adult nonketotic hyperglycinemia nkh crisis presenting. Prognosis of patients with nonketotic hyperglycinemia, is. Nonketotic hyperglycinemia definition of nonketotic. For parents the foundation for nonketotic hyperglycinemia. The treatment for nonketotic hyperglycinemia is based on. It leads to the accumulation of glycine in the body tissues, blood, and cerebrospinal fluid csf. Seizures, hypotonia, lethargy, and hiccups are the principal symptoms, and many. Patients and consumers with specific questions about a genetic test should contact a. Nonketotic hyperglycinemia is listed as a rare disease by the office of rare diseases ord of the national institutes of health nih. Nonketotic hyperglycinemia, also known as glycine encephalopathy, is a genetic disorder distinguished by the accumulation of glycine in body tissues.
Hyperglycinemia was induced in healthy vervet monkeys when treated with a single oral dose of 50 mgkg valproate. Glycine encephalopathy also known as nkh is a rare. Glycine also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. Neonataltype nonketotic hyperglycinemia treatment remains unsatisfactory, even if started early. People magazine turns spotlight on rare diseases with personal stories from country music star randy rogers and model lauren wasser written by lisa sencen on june 26, 2015. Glycine encephalopathy, hiccups, nonketotic hyperglycinemia. Hyperglycinemia symptoms, diagnosis, treatments and causes. Nonketotic hyperglycinemia, also known as glycine encephalopathy mendelian inheritance in man 605899, is an inborn metabolic disorder caused by a glycine cleavage system deficiency. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. Clinical symptoms in atypical nonketotic hyperglycinemia nkh are heterogeneous, in sharp.
Despite this clinical phenotype and a csfplasma ratio confirming a mild variant, measurement of hepatic glycine cleavage activity and the pprotein component indicated the more severe. Variant non ketotic hyperglycinemia is caused by mutations. Our family became familiar with nkh nonketotic hyperglycinemia soon after the arrival of our third child, fiona. Glycine also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the. Early myoclonic encephalopathy and nonketotic hyperglycinemia. Non ketotic hyperglycinemia hlp, 400 g pristine organics. He presented with severe hypotonia, progressive apneic episodes, and erratic myoclonus. A diagnosis of nonketotic hyperglycinemia was made from the mri and the elevated glycine ratio between the csf and plasma. In classical neonatal nkh, levels of cerebrospinal fluid csf glycine and csfplasma glycine ratio are very high but the csf. Biochemical diagnosis of nonketotic hyperglycinemia in cuba.
Nonketotic hyperglycemic hemichorea radiology reference. Nonketotic hyperglycinemia nkh is a metabolic disorder in children which prevents their little bodies from processing glycine. Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. Nonketotic hyperglycinemia nord national organization. An acute dose of 50 mgkg paracetamol increased oxoproline in the urine. Nonketotic hyperglycemic hemichorea is most frequently reported in elderly patients, typically asian, who have type 2 diabetes mellitus, although this may represent publication bias 2. Nih does not independently verify information submitted to the gtr. Nonketotic hyperglycinemia was diagnosed in identical twins with lethargy and respiratory failure in the neonatal period. Atypical variants of nonketotic hyperglycinemia sciencedirect. Biochemical diagnosis of nonketotic hyperglycinemia in. The classical form is then further divided into severe. The glycine cleavage system was investigated in the livers and brains of two patients with typical nonketotic hyperglycinemia who died in the neonatal period.
Nonketotic hyperglycinemia nord national organization for. Nonketotic hyperglycinemia may have serious consequences. Our son, mikaere was born in october 2016 with nonketotic hyperglycinemia, an incredibly rare metabolic disorder which prevents him from processing glycine. Nonketotic hyperglycinemia rare and neglected diseases. Nonketotic hyperglycinemia nkh is an autosomal recessive disorder caused by a defect in glycine cleavage enzyme. We describe a newborn boy with early myoclonic encephalopathy caused by nonketotic hyperglycinemia. Autopsy revealed slightly retarded myelination and severe spongy change in the well. We report on a patient with mild episodic nonketotic hyperglycinemia nkh on valproate who developed episodes of encephalopathy and chorea provoked. Here we report 2 neonates who were admitted to the hospital with complaints of respiratory failure and myoclonic seizures with an elevated cerebrospinal fluidplasma.