We present three babies who presented in neonatal life with hiccups who later were diagnosed with NKH. Two babies presented on the 2 nd day of life with hypotonia, poor feeding, and abnormal movements including jitteriness, hiccups, and twitching. [pediatricneurosciences.com]

Most patients present in the neonatal period. Greater than 80% of patients presenting in this time have a severe form of NKH and approximately 15% have a milder form of the disease. [cancertherapyadvisor.com]

Two had newborn glycine levels above our cut-off and presented within 72 h. The remaining patients could not have been diagnosed by newborn screening without an unacceptably high recall rate. [ncbi.nlm.nih.gov]

Background and Clinical Presentation: Our patient was born as a second child with a normal Apgar score, was active for 2 hours, and became progressively hypotonic and comatose with hiccups and central apnea. [ajnr.org]

Initially, these patients present with the same symptoms and laboratory results that are seen in the classical presentation. [nkh-network.org]

• Increased Susceptibility to Infections

  One form is characterized by episodic vomiting, lethargy, dehydration, ketosis, and increased susceptibility to infection; a second form by generalized hypotonia, lethargy, absence of reflexes, and periodic myoclonic jerks. [medical-dictionary.thefreedictionary.com]

• Respiratory Distress

  The second infant had seizures, hypotonia, and respiratory distress shortly after birth. She was treated with phenobarbital and diphenylhydantion, which had no effect on her seizures. [pediatrics.aappublications.org]

  A female presented on the 3rd day of life with hypotonia, seizures and respiratory distress was treated with phenobarbital and Dilantin with poor response. [nature.com]

  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. [ncbi.nlm.nih.gov]

  Neonatal presentation takes the form of seizures, dystonia, encephalopathy and respiratory distress 2. Outcomes of the disorder are poor with most children dying within the first year and those surviving having severe neurodevelopmental delay. [eurorad.org]

  Patient education To improve patient outcome, educate the patient's family to recognize early signs of dehydration, poor feeding, seizures, and respiratory distress. [emedicine.medscape.com]

• Respiratory Insufficiency

  Conclusion: Inborn errors of metabolism (non-ketotic hyperglycinemia) have to be taken into the differenzial diagnosis of the severely floppy infant with respiratory insufficiency. [thieme-connect.com]

• Blurred Vision

  Abstract A 31-year-old man with spastic paraparesis (diagnosed when he was 10 years old) and hyperglycinemia (diagnosed when he was 19 years old) had an intermittently swollen right eye and blurred vision. [ncbi.nlm.nih.gov]

If molecular testing is equivocal, a combination of enzymatic and molecular testing may be necessary. [35] During the workup of a young patient with suspected stroke, exclude other causes of stroke by obtaining blood, brain, vascular, and cardiac studies [emedicine.medscape.com]

However, all reports on anticonvulsive treatment in NKH are single case reports and no long-term studies have been performed in this patient's cohort. Hence, no recommendations for the treatment of epilepsy in NKH are yet available. [content.iospress.com]

Three months after treatment plasma and urine glycine remained elevated, 65.4 μmol/dl and 4590 mg/Gm creatinine, respectively; however, CSF glycine dropped markedly to 8 μmol/dl. [nature.com]

TREATMENT Treatment of NKH is symptom specific. During the first two years of life, treatment sodium benzoate to reduce plasma concentration of glycine. [secure.ssa.gov]

TREATMENT OF THE DISEASE:  No effective treatment for severe NKH exists.  Current treatment of NKH consists of reduction of plama concentration glycine through treating with benzoate and blocking NMDA receptor site. 1. [slideshare.net]

Ongoing controversies regarding etiology, diagnosis, treatment There is debate over treatment and if it should be initiated at all given the poor outcome of patients with NKH. [cancertherapyadvisor.com]

Abstract Abnormalities of the corpus callosum are often associated with a poor prognosis due to the anatomical defect itself and associated anomalies that include malformations and inherited metabolic disorders. [ncbi.nlm.nih.gov]

Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia. Ann Neurol. 2015 Oct;78(4):606-18. [connectingthegrowingbrain.com]

After counseling the parents about the extreme poor prognosis that carries non-ketotic hyperglycinemia, intensive care treatment was withheld and the newborn was given palliative care. [thieme-connect.com]

The question whether a liver transplantation can be performed early in infancy to improve the prognosis is still under investigation. The documents contained in this web site are presented for information purposes only. [orpha.net]

Etiology Mutations in two genes are known to cause glycine encephalopathy: GLDC (9p22) and AMT (3p21.2-p21.1). These genes encode the P-protein and T-protein components of the enzymatic glycine cleavage system (GCS), respectively. [orpha.net]

Ongoing controversies regarding etiology, diagnosis, treatment There is debate over treatment and if it should be initiated at all given the poor outcome of patients with NKH. [cancertherapyadvisor.com]

Etiology and Pathophysiology Propionic acidemia is classified as an inherited, autosomal recessive, organic acid disorder. The metabolism of isoleucine, valine, threonine, and methionine produces propionyl-CoA. [emedicine.medscape.com]

Summary Epidemiology The prevalence rate is probably about 1 in 100,000 live births worldwide. A high prevalence rate is noted in certain countries like Saudi Arabia. [orpha.net]

Epidemiologic studies have revealed the incidence of glycine encephalopathy in Finland is 1/55,000 newborns and a similar study in British Columbia, Canada revealed the incidence to be 1/63,000. [cancertherapyadvisor.com]

Epidemiology Frequency United States The incidence rate is estimated to be approximately 1 per 100,000 live births. [emedicine.com]

Journal Mol Genet Metab 74:139-46 (2001) DOI: 10.1006/mgme.2001.3224 Reference PMID: 8412015 Authors Tada K, Kure S Title Non-ketotic hyperglycinaemia: molecular lesion, diagnosis and pathophysiology. [genome.jp]

I will review the pathophysiology of NKH, methods of diagnosis, and the differential diagnosis. There are a variety of different pharmacologic and alternative therapies for NKH. [connect.springerpub.com]

Nonketotic hyperglycinemia: molecular lesion, diagnosis and pathophysiology. J inherit metabolic diseases 1993; 16: 691-703. (PMID: 8412015 ) [2] Lu FL, Wang PJ, Hwu WL, Tsou Yau KI, Wang TR, Neonatal type of nonketotic hyperglycinemia. [eurorad.org]

Nonketotic hyperglycinemia : pathophysiological role of NMDA-type excitatory amino acid receptors [8]. [wikigenes.org]

Etiology and Pathophysiology Propionic acidemia is classified as an inherited, autosomal recessive, organic acid disorder. The metabolism of isoleucine, valine, threonine, and methionine produces propionyl-CoA. [emedicine.medscape.com]

RECENT RESEARCH : • Paracetamol prevents hyperglycinemia in vervet monkeys treated with valproate :- • Valproate administration increases the level of the inhibitory transmitter, glycine, in the urine and plasma of patients and experimental animals. • [slideshare.net]

Mutations in the PCCA or PCCB genes disrupt the function of the enzyme, preventing these acids from being metabolized. [en.wikipedia.org]

Nonketotic Hyperglycinemia (NKH) is a metabolic disorder in children which prevents their little bodies from processing glycine. NKH usually affects infants and children, appearing shortly after birth. [foundationnkh.org]

In some forms of NKH, detecting the condition early and beginning proper treatment may help prevent or delay some of the severe health outcomes associated with the condition and can increase the quality of life of affected patients. [balancemetanutrition.com]

Mutations in any of these genes prevent the complex decomposes glycine correctly, which can lead to accumulation of glycine to toxic concentrations in the organs and tissues. [ivami.com]