Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three unrelated adult patients with mild hyperglycinemia, infantile hypotonia, mental retardation, behavioral hyperirritability, and aggressive outbursts were screened for glycine decarboxylase (GLDC) mutations; two novel missense mutations (A389V and R739H) were found. Both mutations had a 6 to 8% of normal GLDC activities when expressed in COS7 cells.
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PMID:Glycine decarboxylase mutations: a distinctive phenotype of nonketotic hyperglycinemia in adults. 1582 56

Clinical symptoms in atypical nonketotic hyperglycinemia (NKH) are heterogeneous, in sharp contrast to uniform severe neurological symptoms in the classical NKH. A review of the literature of atypical NKH cases reveals three forms: neonatal, infantile, and late onset. The presentation in the neonatal form is similar to the classical one but the subsequent outcome is significantly better. Mental retardation and behavioral abnormalities are prevalent in both infantile and late onset forms although the phenotype in late onset atypical NKH is more heterogeneous. Patients with the atypical NKH tend to have a lower CSF/plasma glycine ratio when compared with the classical form, but overlap occurs. Hyperglycinemia in the neonatal and infantile atypical NKH, similar to the classical form, is caused by a deficient glycine cleavage system, whereas the cause of hyperglycinemia in late onset atypical NKH is unknown. A mutation of the T-protein AMT gene and several mutations of P-protein GLDC gene have been identified in homozygous or compound heterozygous state. Some of the GLDC mutations are associated with residual glycine decarboxylase activity when expressed in COS7 cells and early therapeutic intervention may be crucial to improve the outcome in patients harboring such mutations. Identification of more mutations causing atypical NKH and information about the mutations' effect on enzyme activity may help to predict patients with a milder phenotype as well as those who may respond to early therapeutic intervention.
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PMID:Atypical variants of nonketotic hyperglycinemia. 1615 95

Nonketotic hyperglycinemia (NKH), or glycine encephalopathy, is an autosomal recessive disorder caused by a defect in the glycine cleavage enzyme system. In neonatal-onset NKH, patients manifest lethargy, hypotonia, apnea, and intractable epileptic seizures that are not specific to this disease. We experienced a 6-year-old girl with spastic quadriplegia, intractable epilepsy, and mental retardation, all initially regarded as sequelae of neonatal meningitis. The seizure frequency was transiently increased when valproate was started. Head MRI revealed progressive brain atrophy and white matter loss with high intensity signals on T2-weighted and diffusion-weighted images, which prompted us to conduct further metabolic workups. High glycine levels led us to suspect NKH, and we confirmed this diagnosis by the non-invasive, (13)C-glycine breath test. DNA sequencing revealed novel Leu885Pro/Trp897Cys mutations in the glycine decarboxylase gene that were transmitted from both parents. Sodium benzoate and dextromethorphan dramatically decreased her hypertonicity. Our case shows that paradoxical increases in seizure frequency following valproate can be a clue for a diagnosis of NKH, and that a correct diagnosis of NKH can greatly alter the quality of life in such patients.
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PMID:Paradoxical increase in seizure frequency with valproate in nonketotic hyperglycinemia. 2131 84