Two novel laboratory tests facilitating diagnosis of glycine encephalopathy (nonketotic hyperglycinemia)

2011 ◽  
Vol 33 (9) ◽  
pp. 753-757 ◽  
Author(s):  
Shigeo Kure
Keyword(s):  
Laboratory Tests ◽  
Glycine Encephalopathy ◽  
Nonketotic Hyperglycinemia

Atypical Nonketotic Hyperglycinemia

2016 ◽  
Author(s):  
Argirios Dinopoulos
Keyword(s):  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Psychiatric Symptoms ◽  
Late Onset ◽  
Glycine Cleavage System ◽  
Glycine Encephalopathy ◽  
The Central Nervous System ◽  
Glycine Cleavage ◽  
Nonketotic Hyperglycinemia ◽  
Chronic Course

Nonketotic hyperglycinemia (NKH) or glycine encephalopathy (GE) is an autosomal recessive inborn error of glycine degradation due to a defect in the glycine cleavage system (GCS). Accumulation of glycine, particularly in the central nervous system, leads to a variety of neurological symptoms, which may be progressive in infants. Clinical symptoms in atypical NKH are heterogeneous and, according to the age of presentation, cases can be divided in three forms: neonatal, infantile, and late onset. Late-onset atypical cases display an intermittent or a chronic course and may become apparent in adulthood. Psychiatric symptoms are common, and diagnosis may be difficult due to the rarity of the disorder. The CSF/plasma glycine ratio is diagnostic but in atypical cases is usually lower than the diagnostic cut-point for classical NKH. Treatment consists of dietary measures, but no consistent outcomes have been reported.

scholarly journals Glycine Transporter 1 Encephalopathy From Biochemical Pathway to Clinical Disease: Review

2019 ◽  
Vol 6 ◽  
pp. 2329048X1983148 ◽  
Author(s):  
Rayan Alfallaj ◽  
Majid Alfadhel
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Serum ◽  
Global Developmental Delay ◽  
Disease Phenotypes ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
Glycine Encephalopathy ◽  
Severe Hypotonia ◽  
Musculoskeletal Abnormalities ◽  
Nonketotic Hyperglycinemia

Glycine transporter 1 encephalopathy (OMIM# 617301; glycine encephalopathy with normal serum glycine, GLYT1 transporter dysfunction, and nonketotic hyperglycinemia) is caused by mutations in the SLC6A9 gene. To date, 6 cases have been reported in the literature, characterized as having neonatal onset, respiratory failure that required mechanical ventilation, severe hypotonia at birth that progressed to limb hypertonicity, and startle-like responses provoked by sudden loud noises and tactile stimulation. Additional characteristics included dysmorphic features, musculoskeletal abnormalities, and abnormal antenatal findings. Initial diagnosis include elevated levels of glycine in cerebrospinal fluid and an elevated cerebrospinal fluid to plasma glycine ratio. Abnormal magnetic resonance imaging findings included white matter abnormalities, thin corpus callosum, dilatation of the lateral and third ventricles, caudate atrophy, and tiny cysts. Patients reported so far showed normal electroencephalogram results. Treatment was supportive and appeared severe as 50% of the patients died between 2 days and 7 months of age, while surviving children had global developmental delay. In this report, we reviewed the published cases having glycine transporter 1 encephalopathy and retrospectively characterizing the disease phenotypes, affected biochemical pathways, neuroradiological abnormalities, diagnosis, genetic issues, and treatment; additionally, key discussion points are also presented.

Nonketotic Hyperglycinemia (Glycine Encephalopathy) and Lipoate Deficiency Disorders

2016 ◽  
pp. 349-356 ◽  
Author(s):  
Johann L.K. Van Hove ◽  
Julia B. Hennermann ◽  
Curtis R. Coughlin II
Keyword(s):  
Glycine Encephalopathy ◽  
Nonketotic Hyperglycinemia

Homozygous Novel Variants in the Glycine Decarboxylase Gene Associated with Nonketotic Hyperglycinemia in a Distinct Population

2021 ◽  
Author(s):  
Heba Salah Abdelkhalek Elabd ◽  
Fatma Bastaki ◽  
Mohamed Khalifa
Keyword(s):  
Middle Eastern ◽  
In Silico Analysis ◽  
Autosomal Recessive Disorder ◽  
Missense Variant ◽  
Primary Defect ◽  
Pathogenic Variants ◽  
Glycine Encephalopathy ◽  
Novel Variants ◽  
Glycine Cleavage ◽  
Nonketotic Hyperglycinemia

AbstractGlycine encephalopathy (GE), also known as nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder due to a primary defect in the glycine cleavage enzyme system. It is characterized by elevated levels of glycine in the plasma and cerebrospinal fluid (CSF) and increased CSF to plasma glycine ratio.Mutations in three genes of the mitochondrial glycine cleavage system have been found to cause NKH. Most patients have a mutation in the GLDC.In this report, we present five new patients from Middle Eastern families with NKH. They were all born to consanguineous parents and two of them have family history of similarly affected sibling(s). All patients presented with neonatal encephalopathy associated with seizures. Their diagnoses were suspected clinically and confirmed biochemically.DNA sequence analysis of the five patients revealed five different pathogenic or likely pathogenic variants in the GLDC. Three were missense variants (c.2675C > T; p.Ala892Val), (c.2512A > G; p.Asn838Asp), and (c.2943A > C; p.Lys981Asn); one was an intronic missense variant (c.1402–2A > T) leading to an exonic deletion, and one was a deletion of 42 amino acids (c.1927-?_2052 + ?del.) All variants were novel and homozygous. The pathogenicity of these variants was determined according to the American College of Medical Genetics (ACMG) variant classification and in silico analysis. Another novel homozygous variant (c.1384C > G; p.Leu462Val) was detected, which was classified as likely benign.The novel variants identified in the GLDC in these patients underlie the pathogenesis of NKH, specifically for the Middle Eastern population. This expands the mutation spectrum of NKH to include a distinct ethnic population that has not been studied before.

scholarly journals Identification of Two Novel Mutations in Aminomethyltransferase Gene in Cases of Glycine Encephalopathy

2018 ◽  
Vol 07 (03) ◽  
pp. 097-102
Author(s):  
Lokesh Lingappa ◽  
Shaik Naushad ◽  
Akella Radha Rama Devi
Keyword(s):  
Carbon Metabolism ◽  
Gene Mutations ◽  
Novel Mutations ◽  
The Third ◽  
Glycine Encephalopathy ◽  
Exome Analysis ◽  
Methylene Tetrahydrofolate ◽  
One Carbon Metabolism ◽  
Nonketotic Hyperglycinemia

AbstractIn this study, we report three cases of nonketotic hyperglycinemia (NKHG) diagnosed biochemically and molecularly. Clinical exome analysis in two families revealed two novel mutations in the aminomethyltransferase (AMT) gene, that is, c.14_15insT (p.Ser6LysfsTer22) and c.259–2A > T, both of them adversely affecting the protein. This is the first report of AMT gene mutations in NKHG from India. Prenatal diagnosis in the first family showed an unaffected fetus in the third pregnancy. The role of AMT protein is pivotal for the synthesis of 5,10-methylene tetrahydrofolate, the first metabolite in one-carbon metabolism that regulates DNA synthesis, repair, and methylation.

Neuroimaging Spectrum of Inherited Neurotransmitter Disorders

2019 ◽  
Vol 51 (01) ◽  
pp. 006-021
Author(s):  
Yi Ting Lim ◽  
Kshitij Mankad ◽  
Maria Kinali ◽  
Ai Peng Tan
Keyword(s):  
Current Knowledge ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Diagnostic Algorithm ◽  
Deficiency Syndrome ◽  
Imaging Features ◽  
Gamma Aminobutyric Acid ◽  
Case Examples ◽  
Glycine Encephalopathy ◽  
Nonketotic Hyperglycinemia

AbstractInherited neurotransmitter disorders are rare neurometabolic conditions which encompass genetic disorders of neurotransmitter metabolism or transport. The clinical manifestations of these rare disorders are often nonspecific, ranging from encephalopathies and seizures to movement disorders. As a consequence, neurotransmitter disorders are underrecognized and often misdiagnosed. Accurate and timely diagnosis is, however, of utmost importance, given the availability of therapeutic strategies. A high index of clinical suspicion and familiarity with the neuroimaging phenotypes is therefore crucial. While the imaging features of various neurotransmitter disorders often overlap and are nonspecific, imaging can be helpful in providing useful clues to guide the diagnostic algorithm for uncommon conditions in a neonate presenting with nonspecific neurological symptoms. In this review paper, we aim to bring together current knowledge of neuroimaging phenotypes associated with inherited (primary) disorders of neurotransmitter biosynthesis. Magnetic resonance imaging phenotypes of disorders of monoamine biosynthesis, primary cerebral folate deficiency, disorders of pyridoxine metabolism, disorders of gamma-aminobutyric acid metabolism, nonketotic hyperglycinemia (glycine encephalopathy), disorders of serine biosynthesis, and cerebral creatine deficiency syndrome will be discussed and illustrated with case examples.

Critical limb ischaemia in diabetes: definition, assessment, prognosis

VASA ◽  
2001 ◽  
Vol 30 (Supplement 58) ◽  
pp. 21-27
Author(s):  
Luther
Keyword(s):  
Diabetic Foot ◽  
Laboratory Tests ◽  
Critical Limb Ischaemia ◽  
Limb Ischaemia ◽  
Clinical Use ◽  
Arterial Reconstruction ◽  
Arterial Circulation ◽  
Diabetic Foot Disease ◽  
Foot Disease ◽  
Fontaine Classification

In diabetic foot disease, critical limb ischaemia (CLI) cannot be precisely described using established definitions. For clinical use, the Fontaine classification complemented with any objective verification of a reduced arterial circulation is sufficient for decision making. For scientific purposes, objective measurement criteria should be reported. Assessment of CLI should rely on the physical examination of the limb arteries, complemented by laboratory tests like the shape of the PVR curve at ankle or toe levels, and arteriography. The prognosis of CLI in diabetic foot disease depends on the success of arterial reconstruction. The best prognosis for the patients is with a preserved limb. Reconstructive surgery is the best choice for the majority of patients.

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