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Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency.

Chilosi A, Casarano M, Comparini A, Battaglia FM, Mancardi MM, Schiaffino C, Tosetti M, Leuzzi V, Battini R, Cioni G - Orphanet J Rare Dis (2012)

Bottom Line: However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris, Viale del Tirreno 331, 56128 Calambrone Pisa, Italy.

ABSTRACT

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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Related in: MedlinePlus

VABS profiles in all five patients. After L-Arg supplementation there was an improvement in adaptive skills, more significant for motor and daily living skills. The results are expressed in equivalent age (EA). T0 = baseline; T1, T2, T3: after 12, 24, 36 months of L-Arg supplementation, respectively.
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Figure 3: VABS profiles in all five patients. After L-Arg supplementation there was an improvement in adaptive skills, more significant for motor and daily living skills. The results are expressed in equivalent age (EA). T0 = baseline; T1, T2, T3: after 12, 24, 36 months of L-Arg supplementation, respectively.

Mentions: As indicated in Figure 3, VABS showed, even if in various degrees of difficulty, a similar profile concerning adaptive skills in all patients. This profile was characterized by relatively better skills in daily living and motor abilities scales and lower abilities in communication and socialization, with the exception of P1 who showed a socialization skills score just under daily living skills. After L-Arg supplementation VABS profiles demonstrated an improvement in adaptive skills in all patients, more evident for motor skills, with the exception of P3. In particular, P2 and P4 showed an increment of 20 months and 13 EA months respectively, greater than expected in the lapsed period of one year, especially considering the previous pace of development. Daily living skills also appeared to be positively influenced by L-Arg: P1, P2 and P4 showed an increment of 24, 12 and 14 months respectively. On the contrary socialization skills seemed to receive no or little advantage from the L-Arg supplementation with the exception of P2 who showed a 14 month improvement; likewise communication skills also demonstrated reduced advantages, with the exception of P2 and P4 who showed a remarkable improvement of 31 and 11 months respectively.


Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency.

Chilosi A, Casarano M, Comparini A, Battaglia FM, Mancardi MM, Schiaffino C, Tosetti M, Leuzzi V, Battini R, Cioni G - Orphanet J Rare Dis (2012)

VABS profiles in all five patients. After L-Arg supplementation there was an improvement in adaptive skills, more significant for motor and daily living skills. The results are expressed in equivalent age (EA). T0 = baseline; T1, T2, T3: after 12, 24, 36 months of L-Arg supplementation, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3526552&req=5

Figure 3: VABS profiles in all five patients. After L-Arg supplementation there was an improvement in adaptive skills, more significant for motor and daily living skills. The results are expressed in equivalent age (EA). T0 = baseline; T1, T2, T3: after 12, 24, 36 months of L-Arg supplementation, respectively.
Mentions: As indicated in Figure 3, VABS showed, even if in various degrees of difficulty, a similar profile concerning adaptive skills in all patients. This profile was characterized by relatively better skills in daily living and motor abilities scales and lower abilities in communication and socialization, with the exception of P1 who showed a socialization skills score just under daily living skills. After L-Arg supplementation VABS profiles demonstrated an improvement in adaptive skills in all patients, more evident for motor skills, with the exception of P3. In particular, P2 and P4 showed an increment of 20 months and 13 EA months respectively, greater than expected in the lapsed period of one year, especially considering the previous pace of development. Daily living skills also appeared to be positively influenced by L-Arg: P1, P2 and P4 showed an increment of 24, 12 and 14 months respectively. On the contrary socialization skills seemed to receive no or little advantage from the L-Arg supplementation with the exception of P2 who showed a 14 month improvement; likewise communication skills also demonstrated reduced advantages, with the exception of P2 and P4 who showed a remarkable improvement of 31 and 11 months respectively.

Bottom Line: However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris, Viale del Tirreno 331, 56128 Calambrone Pisa, Italy.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus