Nonketotic hyperglycinemia: Clinical range and outcome of a rare neurometabolic disease in a single-center

Sel, Çiğdem Genç; Kılıç, Mustafa; Yüksel, Deniz; Aksoy, Ayşe; Kasapkara, Çiğdem Seher; Ceylaner, Serdar; Oğuz, Kader K.

doi:10.1016/j.braindev.2018.06.007

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…These patients are given, on average, three or even four AEDs as opposed to patients with attenuated NKH, in whom often only a single drug is required to control seizures [ 1 , 5 ]. Moreover, it has been shown that mutations in the AMT gene require more antiepileptic drugs more often than mutations in the GLDC gene do [ 39 ].…”

Section: Antiepileptic Drugs (Aeds)mentioning

confidence: 99%

Nonketotic Hyperglycinemia: Insight into Current Therapies

Nowak

Chuchra

Paprocka

2022

JCM

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Nonketotic hyperglycinemia (NKH) is a rare inborn error of glycine metabolism that is characterized by the accumulation of glycine in all tissues, especially in the central nervous system (CNS). Based on clinical outcomes, NKH can be divided into two forms, i.e., severe and attenuated NKH. A poor prognosis, including no developmental progress and intractable epilepsy, is typical of severe NKH, whereas patients with the attenuated form present with varied symptoms and neurodevelopmental outcomes. So far, no causal treatment of NKH is known. Currently, the therapy is based on sodium benzoate and NMDA (The N-methyl-D-aspartate receptor) receptor site antagonists (dextromethorphan, ketamine). Different clinical outcomes of the therapy raise doubts about the effectiveness of the treatment. The purpose of this review is to summarize the therapeutic potential, challenges and effectiveness of different NKH therapies.

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Section: Antiepileptic Drugs (Aeds)mentioning

confidence: 99%

Nonketotic Hyperglycinemia: Insight into Current Therapies

Nowak

Chuchra

Paprocka

2022

JCM

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“…This consists of four protein complexes (P, T, H, L), which are encoded by GLDC , AMT , GCSH , and GCSL , respectively 1 . In classical neonatal form, the patients’ symptoms include lethargy, hypotonia, apnea, hiccups, and intractable seizures resulting in severe psychomotor disability 2 . Glycine functions as an inhibitory neurotransmitter in the brainstem and spinal cord, but in an excitatory manner in the cerebral cortex, the result of an agonist effect on N ‐methyl‐ d ‐aspartate receptors (NMDA‐R).…”

Section: Figmentioning

confidence: 99%

Seventeen‐year long‐term survival of a case of neonatal nonketotic hyperglycinemia

Ichikawa

Inami

Kaneko

2020

Pediatrics International

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Nonketotic hyperglycinemia (NKH) is a rare autosomal recessive disorder resulting from a biochemical defect in the glycine cleavage enzyme system. This consists of four protein complexes (P, T, H, L), which are encoded by GLDC, AMT, GCSH, and GCSL, respectively. 1 In classical neonatal form, the patients' symptoms include lethargy, hypotonia, apnea, hiccups, and intractable seizures resulting in severe psychomotor disability. 2 Glycine functions as an inhibitory neurotransmitter in the brainstem and spinal cord, but in an excitatory manner in the cerebral cortex, the result of an agonist effect on N-methyl-D-aspartate receptors (NMDA-R). Current treatment consists of reducing glycine levels with sodium benzoate (250-550 mg/kg/day) and blocking the effect of excess glycine on NMDA-R with dextromethorphan (5-22 mg/kg/day). A high dose of benzoate (550-750 mg/kg/ day) would be attempted for severe NKH patients. Average survival time of neonatal NKH who survived newborn period is reported to be 3 years 11 months (2.3 months to 15 years). 3 The patient was a Japanese male, aged 17 years, who had been followed up since he was a neonate. He was born at 40 weeks gestation, with a normal pregnancy, and delivery was through cesarean section without complications. The patient developed poor sucking, hypotonia, convulsions, and apnea from 2 days of age. General laboratory tests were not remarkable. He was diagnosed with NKH via elevated glycine levels in the cerebrospinal fluid (CSF) at 323.7 lmol/L (normal range: <25 lmol/L) and in the plasma at 1,729.6 lmol/L (normal range: 125-343 lmol/L), with a CSF/plasma glycine ratio of 0.19 (diagnostic values: >0.08). A genetic analysis was performed after obtaining written informed consent from the patient's parents. The patient demonstrated compound heterozygosity for a deletion of exons 3-8 and a novel c.2574T >G (p.Y858X) mutation in the GLDC gene, as well as decreased 13 C-CO 2 exhalation in a 13 C-glycine breath test. The patient was treated with high-dose benzoate (600 mg/kg)

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“…Electroencephalography (EEG) is used to assess brain and seizure activity in NKH. The usual patterns seen are burst-suppression, hypsarrhythmia, and multifocal epileptiform activity [4,5]. Epilepsy of infancy with migrating focal seizures (EIMFS) in NKH has never been described in the literature.…”

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confidence: 99%