Nonketotic hyperglycinemia(NKH)

Etiology :
Nonketotic high glycine hyperlipidemia ( referred NKH) amino acids of congenital metabolic disorders , not only in the blood of glycine (Glycine) increased the concentration of other body fluids including cerebrospinal fluid (CSF) within the glycine concentration is also high, thus causing the central nervous system toxicity , resulting in associated neurological symptoms. The main reason is (glycine cleavage system, GCS) in which an enzyme deficiency, resulting in glycine metabolism can not be accumulated in the body rises . GCS is a line of the body of the enzyme complex , including the four genes on different chromosomes produced enzymes , respectively, P-protein, H-protein, T-protein , and L-protein, in the case of a tetrahydrofolate , the glycine decomposed into ammonia and carbon dioxide ; addition of glycine can also be used as raw material for synthesis of other amino acids , converted into other amino acids . Statistically more than 80 % of patients because of the P protein deficiency disease, other patients mostly T-protein deficiency ( Finland ) . However, in some patients with non-Finnish region , T ratio of protein deficiency even more than half . Some patients if combined with corpus callosum agenesis, it is more likely that the P protein deficiency disease. P protein is glycine decarboxylase (GLDC) gene product ; and T protein aminomethyltransferase (AMT) gene product .
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Incidence :
Non- keto high glycine hyperlipidemia incidence is very low, according to Statistics Finland , the incidence in Finland is approximately every 50,000 live births and one-half , the other races and did not report the incidence estimate should be lower , Taiwan has been found dozens of other cases . ( Metabolic Diseases - Taiwan experience , Chapter IV , non- keto high glycine blood )
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Genetic model :
Autosomal recessive inheritance, both parents of the defective gene with this one , regardless of gender, each tire Jieyou 1/ 4 chance of heritable disease.
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Clinical characterization :
Newborns can be divided according to age of onset type ( more common ) and late-onset , age of onset among newborns in about 1-3 days old , studies statistics more than 66 % of patients within 48 hours of onset of symptoms . Symptoms include :
1 newborn hiccups ( born shortly be observed )
(2) low tension
3 lethargy / listlessness
4 apnea ( breathing apparatus if given promptly , the situation will gradually improve in a month )
5 spits
6 low tension ( first )
7 local or systemic cramps or muscle clonus , seizures ( after )
8 Growth retardation or mental retardation
9 Microcephaly
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Diagnosis:
When the above symptoms occur when the newborn , and ruled out infection, trauma, hypoxic encephalopathy caused by reasons , you should consider this disease. Laboratory diagnosis can be analyzed in plasma and cerebrospinal fluid amino acid composition , if both values ​​have increased glycine and glycine cerebrospinal fluid divided by the value of the blood glycine ratio greater than 0.08 , this disease can be diagnosed . By liver biopsy to confirm the diagnosis need to do GCS liver enzyme activity was measured in patients with type newborns , GCS activity often tends to 0 .
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Treatment:
Direction of the main treatment is to be able to reduce the value of glycine , including dietary intake restrictions , exchange transfusion therapy, administration of ursodeoxycholic acid and glycine combination of the bile , investment promotion glycine with sodium benzoate excreted in the urine , but these methods for reducing the cerebrospinal fluid glycine without much help , so the long-term prognosis is not necessarily helpful . Dextromethorphan ( trade name Medicon) is generally used to cough in these patients using high doses of Dextromethorphan ( 20-35 mg per kg of body weight ) can reduce muscle tension and slow down the phenomenon cramp cramps
Recent studies of GCS gene expression analysis , discovery and nerve cells similar to the distribution of NMDA receptor . Because high cerebrospinal fluid concentrations of glycine will bind and stimulate the NMDA receptor, so you can use this feature to do to treat the symptoms . Dextromethorphan ( slow cramps ) and ketamine ( reduce apnea / suspension ) is a NMDA receptor antagonist , is therefore one of the most commonly used drug of choice . Another combination antiepileptic , also has the effect of symptoms .
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Prognosis:
Prognosis is usually poor , high mortality rate , the survivors will have associated sequelae, including ankylosing quadriplegia , severe developmental delay or mental retardation .
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Medical assistance issues :
Prenatal Genetic Diagnosis:
Chorionic cells can be used to make enzymes measured ( amniotic cells without GCS activity ) , but there is still false positive or false negative problem to be overcome . Gene sequencing method aspects of the inspection , mainly for GLDC and AMT gene exons (Exon) whether the region is mutated , if it is detected large deletions or mutations within the sequence , or the cause of the disease caused by non- genetic , the test can not be detected thereby . If you have children and have found genetic mutations , genetic testing can be used to do prenatal diagnosis.