Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect

Knaap, Marjo S. van der; Verhoeven, Nanda M.; Maaswinkel-Mooij, P. D.; Pouwels, Petra J. W.; Onkenhout, Wim; Peeters, Els; Stöckler‐Ipsiroglu, Sylvia; Jakobs, Cornelius

doi:10.1002/1531-8249(200004)47:4<540::aid-ana23>3.0.co;2-k

Cited by 74 publications

(16 citation statements)

References 14 publications

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“…Taken as a single measure, however, decreased levels of urinary creatinine are not directly indicative of any specific disease state or physiological abnormality in the PDD group. Decreased creatinine excretion has been previously reported in cases of non‐specific learning difficulties and behavioral problems 15 . A number of factors are also known to impact on creatinine excretion.…”

Section: Discussionmentioning

confidence: 88%

Spot urinary creatinine excretion in pervasive developmental disorders

Whiteley¹,

Waring²,

Williams³

et al. 2006

Pediatrics International

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Further studies of protein catabolism and renal function in autism are required to ascertain the relevance of decreased spot urinary creatinine excretion identified in this preliminary study. Issues regarding the use of single urine creatinine measurements and associated confounding variables are discussed in light of the findings, together with recommendations to use other internal or external standards for the quantification of urinary compounds in PDD research.

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Section: Discussionmentioning

confidence: 88%

Spot urinary creatinine excretion in pervasive developmental disorders

Whiteley¹,

Waring²,

Williams³

et al. 2006

Pediatrics International

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“…Only 14 patients having this disease have been published so far [Stöckler et al, 1994;Ganesan et al, 1997;Schulze et al, 1997Schulze et al, , 2003Ensenauer et al, 2000;Leuzzi et al, 2000;Van der Knaap et al, 2000;Korall et al, 2002;Stöckler-Ipsiroglu and Jakobs, 2002]. In this study we report on the clinical outcome and laboratory findings of five (four proven and one presumed) patients with GAMT deficiency who were initially investigated based on a high urine uric acid/creatinine ratio [Caldeira Araú jo et al, 2002].…”

Section: Introductionmentioning

confidence: 92%

“…The clinical phenotype is variable and not yet well defined, but common manifestations are developmental delay or arrest during the first months of life, neurologic deterioration, intractable epilepsy, extrapyramidal movement disorder, speech disability, muscular hypotonia, and weakness [Schulze et al, 1997;Stöckler-Ipsiroglu and Jakobs, 2002;Wyss and Schulze, 2002]. Some patients presented with autistic-like and self-injurious behavior [Ganesan et al, 1997;Van der Knaap et al, 2000;Von Figura et al, 2000]. Diagnosis of GAMT deficiency is currently made by measuring GAA concentrations in plasma and urine [Hunneman and Hanefeld, 1997;Struys et al, 1998;Bodamer et al, 2001].…”

Section: Introductionmentioning

confidence: 99%

Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardation

Araújo

Smit

Verhoeven

et al. 2005

American J of Med Genetics Pt A

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Our study describes the adult clinical and biochemical spectrum of guanidinoacetate methyltransferase (GAMT) deficiency, a recently discovered inborn error of metabolism. The majority of the previous reports dealt with pediatric patients, in contrast to the present study. A total of 180 institutionalized patients with a severe mental handicap were investigated for urine and plasma uric acid and creatinine. Patients with an increased urinary uric acid/creatinine ratio and/or decreased creatinine were subjected to the analysis of guanidinoacetate (GAA). Four patients (three related and one from an unrelated family) were identified with GAMT-deficiency. A fifth patient had died before a biochemical diagnosis could be made. They all had shown a normal psychomotor development for the first year of life, after which they developed a profound mental retardation. Three out of four had convulsions and all four totally lacked the development of speech. Their GAMT activity in lymphoblasts was impaired and two novel mutations were identified: the 59 G > C and 506 G > A missense mutations. Urinary GAA was increased, but highly variable 347-1,624 mmol/mol creat (Controls <150 mmol/mol creat). In plasma and CSF the GAA levels were fairly constant at 17.3-27.0 mumol/L (Controls 1.33-3.33) and 11.0-12.4 mumol/L, respectively (Controls 0.068-0.114). GAMT deficiency in adults is associated with severe mental retardation and absence or limited speech development. Convulsions may be prominent. The nonspecific nature of the clinical findings as well as the limited availability of GAA assays and/or in vivo magnetic resonance spectroscopy of the brain may mean that many more patients remain undiagnosed in institutions for persons with mental handicaps.

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“…The importance of creatine to normal neurological function is clearly demonstrated in patients that have an inborn deficiency of GAMT which leads to an abnormally low biosynthesis of creatine. Patients with GAMT deficiency exhibit clear developmental delays, extrapyramidal movement disorders and seizures (Stockler and Hanefeld 1997; Stockler et al 1997; van der Knaap et al 2000). To further substantiate the importance of creatine in normal neurological function, creatine monohydrate supplementation improves a variety of the neurological impairments in patients afflicted with this rare disorder (Stockler and Hanefeld 1997; van der Knaap et al 2000).…”

Section: Creatine Monohydrate-structure Function and Role In Cellulmentioning

confidence: 99%

Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases

2008

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Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodegenerative disorders may prove to be useful as a therapeutic intervention. Creatine is a molecule that is produced both endogenously, and acquired exogenously through diet, and is an extremely important molecule that participates in buffering intracellular energy stores. Once creatine is transported into cells, creatine kinase catalyzes the reversible transphosphorylation of creatine via ATP to enhance the phosphocreatine energy pool. Creatine kinase enzymes are located at strategic intracellular sites to couple areas of high energy expenditure to the efficient regeneration of ATP. Thus, the creatinekinase/phosphocreatine system plays an integral role in energy buffering and overall cellular bioenergetics. Originally, exogenous creatine supplementation was widely used only as an ergogenic aid to increase the phosphocreatine pool within muscle to bolster athletic performance. However, the potential therapeutic value of creatine supplementation has recently been investigated with respect to various neurodegenerative disorders that have been associated with bioenergetic deficits as playing a role in disease etiology and/or progression which include; Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and Huntington's disease. This review discusses the contribution of mitochondria and bioenergetics to the progression of these neurodegenerative diseases and investigates the potential neuroprotective value of creatine supplementation in each of these neurological diseases. In summary, current literature suggests that exogenous creatine supplementation is most efficacious as a treatment paradigm in Huntington's and Parkinson's disease but appears to be less effective for ALS and Alzheimer's disease.

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Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect

Cited by 74 publications

References 14 publications

Spot urinary creatinine excretion in pervasive developmental disorders

Spot urinary creatinine excretion in pervasive developmental disorders

Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardation

Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases

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