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Glycine and L-arginine treatment causes hyperhomocysteinemia in cerebral creatine transporter deficiency patients.

ABSTRACT: Our aim was to monitor folate status in five creatine transporter deficient (CRTR) patients undergoing glycine/L-arginine (Gly/Arg) therapy after the finding of severe hyperhomocysteinemia in one of these cases.Five male patients (age range: 12-20; median = 13 years) genetically confirmed of CRTR deficiency, who were treated with oral glycine (200 mg/kg/day) and L-arginine (400 mg/kg/day) twice a day for 9 months. Clinical follow-up was done at baseline and every 3 months after the start of the therapy. Serum folate was assayed by automated procedures, and plasma total homocysteine (tHcys) by HPLC with fluorescence detection. The 677C?T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was analyzed by PCR.Case 1 presented severe hyperhomocysteinemia (81 ?mol/L; control values <10.8) 3 months after Gly/Arg therapy. Three out of the other four cases disclosed mildly increased plasma tHcys values. Serum folate was normal in all cases before therapy, but 3 months after, a deficient status was detected in two cases and a clear decrement in the others when compared with baseline conditions. Two cases were homozygous for the 677C?T polymorphism of the MTHFR, presenting the highest plasma tHcys values. In all cases, after 3 months of folate supplementation (5 mg/day), both serum folate and tHcys concentrations returned to normal values.In conclusion, prior to the start of long-term Gly/Arg therapy, the monitoring of folate and plasma tHcys values, together with study of the 677C?T polymorphism of the MTHFR gene, seems necessary in order to correct hyperhomocysteinemia by means of folate supplementation.

SUBMITTER: Villar C

PROVIDER: S-EPMC3509873 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Glycine and L-arginine treatment causes hyperhomocysteinemia in cerebral creatine transporter deficiency patients.

Villar Cristina C Campistol Jaume J Fons Carmen C Armstrong Judith J Mas Anna A Ormazabal Aida A Artuch Rafael R

JIMD reports 20111104

Our aim was to monitor folate status in five creatine transporter deficient (CRTR) patients undergoing glycine/L-arginine (Gly/Arg) therapy after the finding of severe hyperhomocysteinemia in one of these cases.Five male patients (age range: 12-20; median = 13 years) genetically confirmed of CRTR deficiency, who were treated with oral glycine (200 mg/kg/day) and L-arginine (400 mg/kg/day) twice a day for 9 months. Clinical follow-up was done at baseline and every 3 months after the start of the ...[more]

PMID: 23430891

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Project description:BACKGROUND: SLC6A8, an X-linked gene, encodes the creatine transporter (CRTR) and its mutations lead to cerebral creatine (Cr) deficiency which results in mental retardation, speech and language delay, autistic-like behaviour and epilepsy (CRTR-D, OMIM 300352). CRTR-D represents the most frequent Cr metabolism disorder but, differently from Cr synthesis defects, that are partially reversible by oral Cr supplementation, does not respond to Cr treatment even if precociously administrated. The precursors of Cr are the non-essential amino acids Glycine (Gly) and Arginine (Arg), which have their own transporters at the brain-blood barrier level and, therefore, their supplementation appears an attractive and feasible therapeutic option aimed at stimulating Cr endogenous synthesis and, in this way, at overcoming the block of Cr transport within the brain. However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial. METHODS: In this study five Italian male patients affected by CRTR-D were supplemented with oral L-Arg at a dosage of 300?mg/kg/day divided into 3 doses, for 24-36?months. Biochemical and plasmatic amino acids examinations and thyroid hormone dosages were periodically performed. Moreover, Proton and Phosphorus Magnetic Resonance Spectroscopy (MRS) was monitored during follow-up in concurrence with neuropsychological evaluations. RESULTS: During L-Arg treatment a clinical improvement in motor skills and to a lesser extent in communication and attention was observed. In addition, all patients had a reduction in the number and frequency of epileptic seizures. Daily living skills appeared also to be positively influenced by L-Arg treatment. Moreover, Total Cr and especially PhosphoCr, evaluated by proton and phosphorus spectroscopy, showed a mild increase, although well below the normal range. CONCLUSION: This study provides information to support the effectiveness of L-Arg supplement treatment in CTRT-D patients; in fact the syndromic pattern of cognitive and linguistic deficit presented by CRTR-D patients was partially altered by L-Arg supplementation especially at a qualitative clinical level. Oral L-Arg may represent not only a protective factor towards a further cognitive decline, but can lead to the acquisition of new skills.

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Glycine and L-arginine treatment causes hyperhomocysteinemia in cerebral creatine transporter deficiency patients.

Publications

Glycine and L-arginine treatment causes hyperhomocysteinemia in cerebral creatine transporter deficiency patients.

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