Diagnosis, Differential ; Humans ; Hyperglycinemia, Nonketotic ; diagnosis ; etiology ; genetics ; therapy

Nonketotic hyperglycinemia (NKH) is a rare metabolic brain disease caused by deficient activity of the glycine cleveage system. Localized proton MR spectroscopy (echo-time 166 msec), performed in an infant with the typical clinical and biochemical features of neonatal NKH, showed a markedly increased peak intensity at 3.55 ppm, which was assigned to glycine. Serial proton MR spectrosocpic studies indicated that glycine/choline and glycine/total creatine ratios correlated closely with the patient's clinical course. Proton MR spectroscopy was useful for the non-invasive detection and monitoring of cerebral glycine levels in this infant with NKH.
Case Report ; Human ; Hyperglycinemia, Nonketotic/*diagnosis ; Infant, Newborn ; Magnetic Resonance Imaging ; *Magnetic Resonance Spectroscopy ; Male ; Protons

Nonketotic hyperglycinemia (NKH) is a rare, inborn error of metabolism. In this case report, a Chinese male infant was diagnosed with NKH caused by GLDC gene mutation. The clinical characteristics and genetic diagnosis were reported. The infant presented with an onset of early metabolic encephalopathy and Ohtahara syndrome. Both blood and urinary levels of metabolites were in the normal range. Brain MRI images indicated a poor development of corpus callosum, and a burst suppression pattern was found in the EEG. Results of target gene sequencing technology combined with multiplex ligation-dependent probe amplification (MLPA) indicated a heterozygous missense mutation of c.1786 C>T (p.R596X) in maternal exon 15 and a loss of heterozygosity of 4-15 exon gross deletions in paternal GLDC gene. These definite pathogenic mutations confirmed the diagnosis of NKH. The infant's clinical condition was not improved after treatment with adreno-cortico-tropic-hormone, topiramate and dextromethorphan, and he finally died at 4 months of age. Patients with NKH often exhibit complicated clinical phenotypes and are lack of specific symptoms. NKH could be diagnosed by metabolic screening and molecular genetic analysis.
Glycine Dehydrogenase (Decarboxylating) ; genetics ; Humans ; Hyperglycinemia, Nonketotic ; diagnosis ; genetics ; Infant, Newborn ; Male ; Mutation

Nonketotic hyperglycinemia (NKH) is a rare inborn error of amino acid metabolism. A defect in the glycine cleavage enzyme system results in highly elevated concentrations of glycine in the plasma, urine, cerebrospinal fluid, and brain, resulting in glycine-induced encephalopathy and neuropathy. The prevalence of NKH in Korea is very low, and no reports of surviving patients are available, given the scarcity and poor prognosis of this disease. In the current study, we present a patient with NKH diagnosed on the basis of clinical features, biochemical profiles, and genetic analysis. Magnetic resonance spectroscopy (MRS) allowed the measurement of absolute glycine concentrations in different parts of the brain that showed a significantly increased glycine peak, consolidating the diagnosis of NKH. In additional, serial MRS follow-up showed changes in the glycine/creatinine ratios in different parts of the brain. In conclusion, MRS is an effective, noninvasive diagnostic tool for NKH that can be used to distinguish this disease from other glycine metabolism disorders. It may also be useful for monitoring NKH treatment.
Brain ; Follow-Up Studies ; Glycine ; Glycine Dehydrogenase (Decarboxylating) ; Humans ; Hyperglycinemia, Nonketotic ; Korea ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Plasma ; Prevalence ; Prognosis

Nonketotic hyperglycinemia (NKH) is an autosomal recessive hereditary disease caused by a defect in the glycine cleavage system and is classified into typical and atypical NKH. Atypical NKH has complex manifestations and is difficult to diagnose in clinical practice. This article reports a family of NKH. The parents had normal phenotypes, and the older brother and the younger sister developed this disease in the neonatal period. The older brother manifested as intractable epilepsy, severe spastic diplegia, intellectual disability, an increased level of glycine in blood and cerebrospinal fluid, an increased glycine/creatinine ratio in urine, and an increased ratio of glycine concentration in cerebrospinal fluid and blood. The younger sister manifested as delayed language development, ataxia, chorea, mental and behavior disorders induced by pyrexia, hypotonia, an increased level of glycine in cerebrospinal fluid, and an increased ratio of glycine concentration in cerebrospinal fluid and blood. High-throughput sequencing found a maternal missense mutation, c.3006C>G (p.C1002W), and a paternal nonsense mutation, c.1256C>G (p.S419X), in the GLDC gene in both patients. These two mutations were thought to be pathogenic mutations by a biological software. H293T cells transfected with these two mutants of the GLDC gene had a down-regulated activity of glycine decarboxylase. NKH has various phenotypes, and high-throughput sequencing helps to make a confirmed diagnosis. Atypical NKH is associated with the downregulated activity of glycine decarboxylase caused by gene mutations.
Child ; Child, Preschool ; Female ; Glycine Dehydrogenase (Decarboxylating) ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Hyperglycinemia, Nonketotic ; genetics ; Male ; Mutation

This is a report of the biochemical findings in the first diagnosed case of Nonketotic Hyperglycinemia (NKH) in the Philippines. Urine metabolic screening by high voltage electrophoresis showing grossly increased glycine necessitated  confirmation of NKH. Confirmatory analysis was done by paired plasma-cerebrospinal fluid quantitative amino acid analysis using Ultrahigh Performance Liquid Chromatography (UPLC). The result was compatible with the clinical picture of the patient who presented primarily with apnea, seizures, hypotonia and lethargy. This paper emphasizes the importance of locally available biochemical genetic tests in the diagnosis of inborn errors of metabolism.

Human ; Male ; Infant Newborn ; Apnea ; Chromatography, Liquid ; Electrophoresis ; Genetic Testing ; Glycine ; Hyperglycemia ; Hyperglycinemia, Nonketotic ; Lethargy ; Muscle Hypotonia ; Philippines ; Seizures ; Urinalysis

Lethargy in newborns usually indicates central nervous system dysfunction, and many conditions such as cerebrovascular events, infections, and metabolic diseases should be considered in the differential diagnosis. Nonketotic hyperglycinemia is an autosomal recessive error of glycine metabolism, characterized by myoclonic jerks, hypotonia, hiccups, apnea, and progressive lethargy that may progress to encephalopathy or even death. Cerebral sinovenous thrombosis is a rare condition with various clinical presentations such as seizures, cerebral edema, lethargy, and encephalopathy. Here, we report the case of a newborn infant who presented with progressive lethargy. An initial diagnosis of cerebral venous sinus thrombosis was followed by confirmation of the presence of nonketotic hyperglycinemia.
Apnea ; Brain Edema ; Central Nervous System ; Diagnosis ; Diagnosis, Differential ; Glycine ; Hiccup ; Humans ; Hyperglycinemia, Nonketotic* ; Infant, Newborn* ; Lethargy ; Metabolic Diseases ; Metabolism ; Muscle Hypotonia ; Myoclonus ; Seizures ; Sinus Thrombosis, Intracranial ; Thrombosis*

Nonketotic hyperglycinemia is an extremely rare congenital metabolic disorder, which is caused by the lack of a glycine cleavage system. The onset of hyperglycinemic symptom is during the neonatal or early infant period. Progressing grave neuromotor dysfunction is one of the main symptoms. They include myoclonic seizure, hiccup, apnea, decreased deep tendon reflex, lethargy and coma. The prognosis is mostly very poor. Furtherrnore, there aren't any effective treatments for nonketotic hyperglycinemia. To our knowledge, there has been no reported case of nonketotic hyperglycinemia in Korea. We experienced a case of nonketotic hyperglycinemia in a three-day- old boy, who had manifested with intractable seizure, mental alteration, apnea, hiccup and feeding intolerance. Unfortunately, he died of intractable seizure and neuromotor dysfunction at 20 days after birth. We could make an early diagnosis on the basis of clinical suspicion and high glycine signal in both cerebral white matter and basal ganglias with magnetic resonance spectroscopy (MRS), before amino acid analyses of serum and cerebrospinal fluid(CSF) were obtained. We report a Korean case of nonketotic hyperglycinemia with a brief review of literatures.
Apnea ; Basal Ganglia ; Coma ; Early Diagnosis ; Glycine ; Hiccup ; Humans ; Hyperglycinemia, Nonketotic ; Infant ; Korea ; Lethargy ; Magnetic Resonance Spectroscopy* ; Male ; Parturition ; Prognosis ; Reflex, Stretch ; Seizures