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Metabolic Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephanie Grünewald, Alex Broomfield, Callum Wilson
Creatine is required for the formation of creatine phosphate, an important short-term source for cellular energy. There are three known defects of creatine metabolism, arginine glycine amidinotransferase (AGAT), GAMT and creatine transporter defect. The latter is responsible for the transport of creatine across the blood–brain barrier. All three diseases result in decreased cerebral creatine. However, the additional peripheral symptoms seen in GAMT deficiency are thought to arise from the toxicity of accumulating guanidinoacetate. AGAT and GAMT deficiencies are inherited in an autosomal recessive manner, whereas defects in the creatine transporter are due to a defect in the X-linked gene SLC6A8. Several female carriers of SCL6A8 mutation have been recorded having a phenotype of mild learning problems.
Fragile X and X-linked Mental Retardation
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Jacquemont Sebastien, Hagerman Randi, des Portes Vincent
In contrast to the OPHN1 gene, the Creatine transporter (SCL6A8/CT1) gene illustrates the difficulty in defining a pattern of clinical features for a new syndrome diagnosed through a brain proton magnetic resonance spectroscopy revealing the absence of creatine signal (80). Loss of function of the Creatine transporter leads to motor delay and severe MR associated with epilepsy, dystonia, and autistic features (81,82). However, the clinical presentation is not specific enough to define practical guidelines for SCL6A8/CT1 screening. In four families recently diagnosed, no specific clinical feature was described in addition to the MR and severe expressive language impairment (83). Moreover, some carrier females may exhibit a nonspecific mild cognitive impairment (82,83). Proton magnetic resonance spectroscopy remains the only reliable and sensitive way for the diagnosis of creatine deficiency syndromes, which include two autosomal-recessive disorders (GAMT and AGAT deficiencies) in addition to the X-linked Creatine transporter defect (84). Early diagnosis of these conditions can be helpful since GAMT and AGAT deficits are sensitive to exogenous creatine intake (84).
Multi-Criteria Decision Analysis Model for Assessing the Risk from Multi-Ingredient Dietary Supplements (MIDS)
Published in Journal of Dietary Supplements, 2021
Hellen A. Oketch-Rabah, Mary L. Hardy, Allison P. Patton, Mei Chung, Nandakumara D. Sarma, Charlie Yoe, V. A. Shiva Ayyadurai, Mary A. Fox, Scott A. Jordan, Mkaya Mwamburi, Diane R. Mould, Robert E. Osterberg, Corey Hilmas, Ram Tiwari, Luis Valerio, Donnamaria Jones, Patricia A. Deuster, Gabriel I. Giancaspro
Titles and abstracts identified through the literature searches were screened independently by two reviewers, to identify studies that evaluated a combination of two or more of the five ingredients. Discrepancies between the two screeners’ decisions were resolved by consensus after discussions. A web-based citation-screening tool, AbstrakrTM (http://abstrackr.cebm.brown.edu/) was used to facilitate the abstract screening process. Full-text articles of relevant abstracts were reviewed by one investigator and a second investigator confirmed the article’s inclusion based on eligibility criteria outline below (details on Literature search, Selection Process, and Eligibility Criteria are available in Appendix A2, OSM):Human intervention and observational studies including case reports that investigated a combination of two or more of the five ingredients of interest. Studies that included other ingredients of no interest were included except where a constituent was known to have cardiovascular related adverse effects such as Ephedra.Unpublished/other studies identified through reference mining of selected review articles.Criteria for exclusion were:Studies of substances not included in the model that are generally known to be associated with adverse events or banned by regulatory agencies (e.g., ephedra, which was banned by the Food and Drug Administration (FDA) from the US market because of adverse CV effects) (FDA 2004).Study populations with known genetic conditions that can interfere with metabolism of any of the five ingredients of interest (e.g., study population with a transporter defect, affecting one of the ingredients for example creatine transporter defect) (Longo et al. 2011).