Abstract
BackgroundArginine:glycine amidinotransferase deficiency (AGAT-d) is a very rare inborn error of creatine synthesis mainly characterized by absence of brain Creatine (Cr) peak, intellectual disability, severe language impairment and behavioural disorder and susceptible to supplementary Cr treatment per os. Serial examinations by magnetic resonance spectroscopy are required to evaluate Cr recovery in brain during treatment of high doses of Cr per os, which have been proved beneficial and effective in treating main clinical symptoms.A long term study with detailed reports on clinical, neurochemical and neuropsychological outcomes of the first Italian patients affected by AGAT-d here reported can represent a landmark in management of this disorder thus enhancing medical knowledge and clinical practice.ResultsWe have evaluated the long term effects of Cr supplementation management in four Italian patients affected by AGAT-d, correlating specific treatments with serial clinical, biochemical and magnetic resonance spectroscopy examinations as well as the neuropsychological outcome by standardized developmental scales. Consecutive MRS examinations have confirmed that Cr depletion in AGAT-d patients is reversible under Cr supplementation. Cr treatment is considered safe and well tolerated but side effects, including weight gain and kidney stones, have been reported.ConclusionsEarly treatment prevents adverse developmental outcome, while patients diagnosed and treated at an older age showed partial but significant cognitive recovery with clear improvements in adaptive functioning.
Highlights
Arginine:glycine amidinotransferase deficiency (AGAT-d) is a very rare inborn error of creatine synthesis mainly characterized by absence of brain Creatine (Cr) peak, intellectual disability, severe language impairment and behavioural disorder and susceptible to supplementary Cr treatment per os
Arginine:glycine amidinotransferase (AGAT, OMIM 602360) deficiency (AGAT-d) is a very rare inborn error of creatine (Cr) synthesis described in 2000 in an Italian family and successively confirmed by molecular and enzymatic analysis [1, 2]. This disorder is caused by a deficiency of the first enzyme involved in Cr synthesis (Fig. 1), resulting in a commonly recognized biochemical pattern represented by low Guanidinoacetic acid (GAA) concentrations in plasma and urine and low/undetectable
These scales give an overall assessment of cognitive abilities for adults, young children and adolescents, respectively; providing a total score of Intelligence Quotient (TIQ) and four composite scores, which measure specific cognitive domains: Verbal Comprehension (VC), Visual-perceptual Reasoning (VPR), Working Memory (WM) and Processing Speed (PS)
Summary
Arginine:glycine amidinotransferase deficiency (AGAT-d) is a very rare inborn error of creatine synthesis mainly characterized by absence of brain Creatine (Cr) peak, intellectual disability, severe language impairment and behavioural disorder and susceptible to supplementary Cr treatment per os. Arginine:glycine amidinotransferase (AGAT, OMIM 602360) deficiency (AGAT-d) is a very rare inborn error of creatine (Cr) synthesis described in 2000 in an Italian family and successively confirmed by molecular and enzymatic analysis [1, 2]. This disorder is caused by a deficiency of the first enzyme involved in Cr synthesis (Fig. 1), resulting in a commonly recognized biochemical pattern represented by low Guanidinoacetic acid (GAA) concentrations in plasma and urine and low/undetectable. In this paper, we report the clinical data observed in our AGAT-d patients over a long period
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