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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a new creatine metabolism disorder in 2 young sisters who suffered from mental retardation and severe language delay. Blood examination, investigation of the most common neurometabolic disorders, and brain magnetic resonance imaging were normal. Diagnosis was established only by means of in vivo proton magnetic resonance spectroscopy, which disclosed generalized depletion of creatine in the brain. Creatine monohydrate oral administration led to almost complete brain creatine level restoration along with improvement of the patients' disabilities.
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PMID:Reversible brain creatine deficiency in two sisters with normal blood creatine level. 1076 63

Creatine metabolism disorders have so far been described at the level of two synthetic steps, guanidinoacetate N-methyltransferase and arginine:glycine amidinotransferase, and at the level of the creatine transporter 1. Guanidinoacetate N-methyltransferase and arginine:glycine amidinotransferase deficiency respond positively to substitutive treatment with creatine monohydrate. Guanidinoacetate N-methyltransferase deficiency results in a severe neurologic disease (age of onset 3 months to 2 years) characterized by developmental arrest, neurologic deterioration, movement disorders, mental retardation, autistic-like behavior, and epilepsy. Severe early-onset epilepsy with pleomorphic seizures is a key symptom of this disorder. Data suggest that in patients with guanidinoacetate N-methyltransferase deficiency, epilepsy and associated electroencephalographic abnormalities are more responsive to creatine supplementation than to conventional antiepilepsy drugs. Arginine:glycine amidinotransferase and creatine transporter 1 mainly present with mental retardation and severe language disorder. All cases of creatine disorders reported to date have been detected by brain proton magnetic resonance spectroscopy, an expensive technique not routinely used in pediatric neurology. A potential diagnostic strategy to select patients for evaluation using proton magnetic resonance spectroscopy is proposed in this review.
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PMID:Inborn errors of creatine metabolism and epilepsy: clinical features, diagnosis, and treatment. 1259 58

Creatine deficiency syndromes are a newly described group of inborn errors of creatine synthesis (arginine:glycine amidinotransferase (AGAT) deficiency and guanidinoaceteate methyltransferase (GAMT) deficiency) and creatine transport (creatine transporter (CRTR) deficiency). The common clinical denominator of creatine deficiency syndromes is mental retardation and epilepsy, suggesting the main involvement of cerebral grey matter (grey matter disease). Patients with GAMT deficiency exhibit a more complex clinical phenotype with dystonic hyperkinetic movement disorder and epilepsy that in some cases is unresponsive to pharmacological treatment. The common biochemical denominator of creatine deficiency syndromes is cerebral creatine deficiency which is demonstrated by in vivo proton magnetic resonance spectroscopy. Measurement of guanidinoacetate in body fluids may discriminate GAMT (high concentration), AGAT (low concentration) and CRTR (normal concentration). Further biochemical characteristics include changes in creatine and creatinine concentrations in body fluids. GAMT and AGAT deficiency are treatable by oral creatine supplementation, while patients with CRTR deficiency do not respond to this type of treatment. Further recognition of patients will be of major importance for the estimation of the frequency, for the understanding of phenotypic variations and for treatment strategies.
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PMID:Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism. 1288 68

Creatine deficiency syndromes are a newly described group of inborn errors of creatine synthesis (arginine:glycine amidinotransferase (AGAT) deficiency and guanidinoacetate methyltransferase (GAMT) deficiency) and of creatine transport (creatine transporter (CRTR) deficiency). The common clinical feature of creatine deficiency syndromes is mental retardation and epilepsy suggesting main involvement of cerebral gray matter. The typical biochemical abnormality of creatine deficiency syndromes is cerebral creatine deficiency, which is demonstrated by in vivo proton magnetic resonance spectroscopy. Measurement of guanidinoacetate in body fluids may discriminate between the GAMT (high concentration), AGAT (low concentration) and CRTR (normal concentration) deficiencies. Further biochemical characteristics include changes in creatine and creatinine concentrations in body fluids. GAMT and AGAT deficiency are treatable by oral creatine supplementation, while patients with CRTR deficiency do not respond to this type of treatment. The creatine deficiency syndromes are underdiagnosed, so their possibility should be considered in all children affected by unexplained mental retardation, seizures and speech delay.
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PMID:Biochemical and clinical characteristics of creatine deficiency syndromes. 1562 59

Creatine transporter deficiency is an X-linked disorder characterized by mental retardation and language delay. The authors report a patient affected by creatine transport deficiency caused by a novel mutation in the SLC6A8 gene. Impairment in social interaction represents a consistent clinical finding in the few cases described to date and may be a diagnostic clue for creatine transporter deficiency in males affected by mental retardation, seizures, and language impairment.
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PMID:X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation. 1608 85

New metabolic diseases are regularly identified by a genetic or biochemical approach. Indeed, the metabolic diseases result from an enzymatic block with accumulation of a metabolite upstream to the block and deficit of a metabolite downstream. The characterization of these abnormal metabolites by MRI spectroscopy permitted to identify the deficient enzyme in two new groups of diseases, creatine deficiencies and polyol anomalies. Creatine deficiency is implicated in unspecific mental retardation. A low peak of creatine at MRI spectroscopy is evocating of creatine deficiency which is treatable by creatine administration. Deficiency of synthesis of polyols, metabolites on the pentose pathway, represent new described metabolic diseases with variable symptoms including a neurological distress, liver disease, splenomegaly, cutis laxa and renal insufficiency. The deficit of ribose-5-phosphate isomerase, one of the enzymes whose diagnosis is evoked in front of the accumulation of ribitol, arabitol and xylitol leads to a leucodystrophy in adults. This new deficit was highlighted by the identification of an abnormal peak in cerebral MRI-spectroscopy corresponding to the abnormal accumulation of polyols in brain. Congenital hyperinsulinism (HI) is characterized by profound hypoglycaemia related to inappropriate insulin secretion. Focal and diffuse forms of hyperinsulinism share a similar clinical presentation but their treatment is dramatically different. Until recently, preoperative differential diagnosis was based on pancreatic venous sampling, an invasive and technically demanding technique. Positron emission tomography (PET) after injection of [18F]Fluoro-L-DOPA has been evaluated for the preoperative differentiation between focal and diffuse HI, by imaging uptake of radiotracer and the conversion of [18F]Fluoro-L-DOPA into dopamine by DOPA decarboxylase. PET with [18F]Fluoro-L-DOPA has been validated as a reliable test to differentiate diffuse and focal HI and is now a major differential diagnosis tool in infantile hyperinsulinemic hypoglycaemia.
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PMID:[Radiological innovations in the screening and diagnosis of the inborn errors of metabolism]. 1627 50

Guanidinoacetate methyltransferase (GAMT) deficiency (MIM 601240), an autosomal recessive disorder of creatine biosynthesis, presents with mental retardation, extrapyramidal symptoms, autistic-like behavior and epilepsy. Other hallmarks are cerebral creatine deficiency, increased levels of guanidinoacetate in body fluids and mutations in the GAMT gene. Creatine supplementation partially restores cerebral creatine content. Worldwide, 29 patients have been identified and 15 different mutations have been reported in the GAMT gene. Ten out of these 29 patients are of Portuguese origin. Likely, a founder effect and a high carrier rate in Portugal exist, since in 17 out of the 20 Portuguese alleles the c.59G>C; p.Trp20Ser mutation was found. We investigated the carrier rate of the c.59G>C; p.Trp20Ser mutation in different regions of Portugal and confirmed the pathogenic nature of this missense mutation by transient transfections. Anonymous bloodspots (1002) were screened for the presence of the c.59G>C; p.Trp20Ser mutation by SNaPshot (Single Nucleotide Polymorphism Multiplex Kit). Eight carriers of c.59G>C; p.Trp20Ser were detected of which four are derived from the Archipelagos. This suggests that the carrier rate of the c.59G>C; p.Trp20Ser mutation is relatively high in these islands, as well as in other parts of Portugal. It also implies that newborn screening in these regions is warranted for this treatable disorder.
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PMID:A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. 1733 14

Creatine transporter deficiency is an X-linked mental retardation disorder caused by mutations in the creatine transporter gene (SLC6A8). So far, 20 mutations in the SLC6A8 gene have been described. We have developed a diagnostic assay to test creatine uptake in fibroblasts. Additionally, we expanded the assay to characterize novel SLC6A8 missense variants. A total of 13 variants were introduced in the SLC6A8 cDNA by site-directed mutagenesis. All variants were transiently transfected in SLC6A8-deficient fibroblasts and tested for restoration of creatine uptake in deficient primary fibroblasts. Thus, we proved that nine variants (p.Gly87Arg, p.Phe107del, p.Tyr317X, p.Asn336del, p.Cys337Trp, p.Ile347del, p.Pro390Leu, p.Arg391Trp, and p.Pro554Leu) are pathogenic mutations and four variants (p.Lys4Arg, p.Gly26Arg, p.Met560Val, and p.Val629Ile) are nonpathogenic. The present study provides an improved diagnostic tool to classify sequence variants of unknown significance.
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PMID:Functional characterization of missense variants in the creatine transporter gene (SLC6A8): improved diagnostic application. 1746 20

Creatine transporter deficiency is an X-linked mental retardation disorder caused by mutations in the creatine transporter gene, SLC6A8. In a European Mental Retardation Consortium panel of 66 patients, we identified a male with mental retardation, caused by a c.1059_1061delCTT; p.Phe354del mutation in the SLC6A8 gene. With the use of direct DNA sequencing, the mutation was also found in the brother of the proband, but not in their mother. However, by analyzing EDTA blood of the mother with denaturing high-performance liquid chromatography (DHPLC), we could show that the mother displays low-level somatic mosaicism for the three base-pair deletion. This study indicates DHPLC as an important tool in the detection of low-level mosaicism, as does it illustrate the importance of considering somatic and germline mosaicism in the case of apparent de novo mutation.
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PMID:Detection of low-level somatic and germline mosaicism by denaturing high-performance liquid chromatography in a EURO-MRX family with SLC6A8 deficiency. 1835 Mar 23

Creatine transporter deficit (CT1) is an inherited metabolic disorder that causes mental retardation, epilepsy, speech, language and behavioral deficits. Until now, no treatment has been proven to be successful for this condition. We describe 1-year follow-up study of a child, aged 9.6 years, with CT1 defect, on oral supplementation with L-arginine, a precursor of creatine synthesis. Under supplementation, he showed a noticeable improvement of neurological, language and behavioral status and an increase of brain creatine and phosphocreatine documented with magnetic resonance spectroscopy. The results suggest that children with CT1 disorder show some residual adaptive plasticity for certain functions even at quite an advanced age. Further trials with higher L-arginine dosages and more protracted treatment are encouraged.
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PMID:Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect. 1856 40


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