Arginine supplementation in four patients with X‐linked creatine transporter defect

Fons, Carmen; Sempere, A.; Arias, Ángela; López-Sala, Anna; Póo, Pilar; Pineda, Merçè; Mas, Anna; Vilaseca, M. A.; Salomons, Gajja S.; Ribes, Antònia; Artuch, Rafael; Campistol, Jaume

doi:10.1007/s10545-008-0902-1

Cited by 50 publications

(45 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, it has been suggested that L-arginine treatment alone might also increase these demands (Jahangir et al 2009), elevating plasma total homocysteine (tHcys)/methionine ratio. In our own experience, during the period of 2007-2008, we treated our CRTR-deficient patients with L-arginine alone (Fons et al 2008), but we did not detect low plasma methionine or decreased serum folate values (data not shown). In this report, our aim was to monitor folate status in five CRTR patients undergoing Gly/Arg therapy after the serendipitous finding of severe hyperhomocysteinemia in one of these cases.…”

Section: Introductionmentioning

confidence: 79%

“…Patients were treated with oral glycine (200 mg/kg/day) and L-arginine (400 mg/kg/day), twice a day for 6 months, according to previously reported experiences (Fons et al 2008;Battini et al 2010). No other changes in patient treatment or diet were made during this time.…”

Section: Methodsmentioning

confidence: 99%

“…Clinical, biochemical, and molecular data of the patients have been published elsewhere (Fons et al 2008). Written informed consent was obtained from parents of the patients before treatment.…”

Section: Patientsmentioning

confidence: 99%

“…In GAMT deficiency, this treatment may be combined with ornithine supplementation and arginine restriction. Different therapeutic approaches have been tried (Fons et al 2008;Battini et al 2010), but with no significant improvement in the neurological outcome. Recently, the association between glycine and L-arginine (Gly/Arg), with the rationale of increasing creatine syntesis from guanidinoacetate in the brain, has been assayed in several studies of patients (Leuzzi et al 2008;MercimekMahmutoglu et al 2010), although no definitive results concerning neurological outcome have been published yet.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Glycine and l-Arginine Treatment Causes Hyperhomocysteinemia in Cerebral Creatine Transporter Deficiency Patients

Villar¹,

Campistol²,

Fons³

et al. 2011

JIMD Reports

View full text Add to dashboard Cite

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 ¼ 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 followup 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 mmol/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.

show abstract

Section: Introductionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Glycine and l-Arginine Treatment Causes Hyperhomocysteinemia in Cerebral Creatine Transporter Deficiency Patients

Villar¹,

Campistol²,

Fons³

et al. 2011

JIMD Reports

View full text Add to dashboard Cite

show abstract

“…Guanidinoacetic acid, a direct precursor of creatine, improved work capacity in women with chronic fatigue syndrome yet markers of tissue bioenergetics were not improved by the intervention (Ostojic et al 2016), suggesting non-energy related role of this compound. Oral L-arginine, another precursor of creatine, positively affected energy metabolism in MELAS syndrome, an inherited disorder of mitochondrial energy metabolism (Rodan et al 2015), while its effectiveness to improve brain bioenergetics in patients with X-linked creatine transporter defect was absent (Fons et al 2008) or minimal (Chilosi et al 2012). Improved muscle bioenergetics and mitochondrial function have been reported recently in children suffering from Duchenne muscular dystrophy treated with L-arginine and metformin for 16 weeks (Hafner et al 2016).…”

Section: Tackling Impaired Bioenergeticsmentioning

confidence: 98%

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

Ostojić

2017

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Mitochondrial energy deficit is considered a key element of different clinical pathologies -from inherited disorders of energy metabolism to drug-induced mitochondrial toxicity, to cardiometabolic and neurodegenerative diseases. However, clinical manifestations of impaired bioenergetics are not easy to recognize, with patient-reported features usually include non-pathognomonic fatigue and weakness, or exercise intolerance, while specific lab tests are missing. Although it is not clear whether poor energetics is a primary deficit or a secondary consequence of specific disorders, improving mitochondrial viability remains a challenging task in both experimental and clinical medicine. In this review, biochemical and clinical evidence of energy deficits were reviewed, along with possible therapeutic options to tackle energy failure and restore bioenergetics.

show abstract

Disorders of creatine transport and metabolism

Longo

Ardon

Vanzo

et al. 2011

American J of Med Genetics Pt C

View full text Add to dashboard Cite

Creatine is a nitrogen containing compound that serves as an energy shuttle between the mitochondrial sites of ATP production and the cytosol where ATP is utilized. There are two known disorders of creatine synthesis (both transmitted as autosomal recessive traits: arginine: glycine amidinotransferase (AGAT) deficiency; OMIM 602360; and guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 601240)) and one disorder of creatine transport (X-linked recessive SLC6A8 creatine transporter deficiency (OMIM 300036)). All these disorders are characterized by brain creatine deficiency, detectable by magnetic resonance spectroscopy. Affected patients can have mental retardation, hypotonia, autism or behavioral problems and seizures. The diagnosis of these conditions relies on the measurement of plasma and urine creatine and guanidinoacetate. Creatine levels in plasma are reduced in both creatine synthesis defects and guanidinoacetate is increased in GAMT deficiency. The urine creatine/creatinine ratio is elevated in creatine transporter deficiency with normal plasma levels of creatine and guanidinoacetate. The diagnosis is confirmed in all cases by DNA testing or functional studies. Defects of creatine biosynthesis are treated with creatine supplements and, in GAMT deficiency, with ornithine and dietary restriction of arginine through limitation of protein intake. No causal therapy is yet available for creatine transporter deficiency and supplementation with the guanidinoacetate precursors arginine and glycine is being explored. The excellent response to therapy of early identified patients with GAMT or AGAT deficiency candidates these condition for inclusion in newborn screening programs.

show abstract

Arginine supplementation in four patients with X‐linked creatine transporter defect

Abstract: Nine months of L-arginine supplementation did not show effectiveness in the four patients affected with CRTR-D in this protocol.

Cited by 50 publications

References 22 publications

Glycine and l-Arginine Treatment Causes Hyperhomocysteinemia in Cerebral Creatine Transporter Deficiency Patients

Glycine and l-Arginine Treatment Causes Hyperhomocysteinemia in Cerebral Creatine Transporter Deficiency Patients

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

Disorders of creatine transport and metabolism

Contact Info

Product

Resources

About