Examining Special Nutritional Requirements in Disease States Proceedings of a Workshop (2018) / Chapter Skim
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2 Addressing Nutrient Needs Due to Loss of Function in Genetic Diseases
2 Addressing Nutrient Needs Due to Loss of Function in Genetic Diseases
Pages 19-38
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From page 19... ...
, discussed the contributions of nutrients in complex inborn errors of metabolism, using methylmalonic acidemia (MMA) as a case example.
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Evidence suggests both causality and an intake–response relationship with respect to the toxicity of Phe in PKU. Phe intake that exceeds anabolic needs increases Phe concentrations in blood and brain, resulting in profound cognitive impairment if PKU is not treated with a low Phe diet started shortly after birth.
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. The organization recommends a 20 to 50 percent higher protein intake when amino acid medical foods provide the primary source of protein, based on the body's rapid absorption and oxidation of amino acids, resulting in reduced protein synthesis.
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Ney went on to explain that despite almost 50 percent lower intake of tyrosine with GMP compared to amino acid medical foods, fasting plasma tyrosine levels are not different and within the normal range. These findings were reinforced by a 13-month study from Portugal that demonstrated increased mean blood tyrosine levels in study participants with PKU using daily servings of GMP medical foods (Pinto et al., 2017)
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• More needs to be learned about how the unique nutritional man agement approaches in conditions like PKU affect the gut micro biota, in particular, nutrient bioavailability, the synthesis of both beneficial metabolites, such as short-chain fatty acids, and also potentially harmful metabolites. • The concept of conditionally essential nutrients in PKU, with altered metabolism and inflammation or oxidative stress, dietary acid load, and bone health, also has relevance for chronic conditions.
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Many people have tried to identify a universal biomarker for mitochondrial disease, but unfortunately, no single biomarker exists because of the many different genes that can be involved in causing mitochondrial diseases. Gene mutations that cause primary mitochondrial disease may occur both in the deoxyribonucleic acid (DNA)
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Nature Reviews Disease Primers. Mitochondrial diseases, Gorman, G
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. For the past decade, amino acid therapies have focused on arginine and citrulline.
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Furthermore, patients with acute metabolic stressors that may cause neurodevelopmental regression with decompensation, such as a fever or an infection, are often given glucose-containing fluids to prevent catabolism. Concerns have arisen about acute glucose infusion precipitating a metabolic crisis due to the increased nicotinamide adenine dinucleotide + hydrogen (NADH)
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In addition, good fluid intake is recommended, with increased fluid given when needed for heat, activity, or metabolic stress occurs. Novel Treatment Strategies Novel treatment strategies being considered to treat mitochondrial disease include genetic correction strategies as well as small molecular approaches, metabolic manipulation, and diet and exercise to treat the secondary cell consequences of the disease.
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Monogenic mitochondrial disorders. Volume 366, page 1139.
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CONTRIBUTION OF NUTRIENTS IN COMPLEX INBORN ERRORS OF METABOLISM: THE CASE OF METHYLMALONIC ACIDEMIA5 MMA is a disorder of essential amino acid and odd chain fatty acid metabolism in humans. In essence, Venditti explained, four of the amino acids that are metabolized by the Krebs cycle -- methionine, isoleucine, threonine, and valine, which are called propiogenic amino acids -- annot c be oxidized because they lack their co-factor ado-cbl and instead they produce toxic acids in the body, such as methylmalonic acid.
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Medical Nutrition Therapy to Treat Methylmalonic Acidemia As mentioned, a frequent diet for MMA patients is a relatively low protein diet to restrict the propiogenic precursors, the amino acids valine, isoleucine, methionine, or threonine, and a medical food also without those amino acids (Manoli et al., 2016a,b)
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. However, Venditti's analysis showed p that the branched chain amino acid ratios in these patients were altered, probably because of the intake of medical foods.
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Venditti's research group and other centers have been able to correct the branched chain amino acids deficiency syndromes in MMA patients by lowering the medical foods and lowering amino acid intake (Manoli et al., 2016a,b)
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In the early days of treating PKU, children died because all Phe was restricted; tyrosine then became a relative essential amino acid in that setting because Phe was restricted. This also proved that co-factors can be effective in some cases.
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Methylmalonic Acidemia Berry stated that Venditti provided an excellent review of the importance of targeting medical foods to a disease so they do not result in amino acid imbalances. She noted that the lack of sufficiently large cohorts and the lack of financial resources to study these issues are difficult problems to resolve.
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the fact that nutritional needs change throughout the patient's lifespan. In terms of what is next in nutrition care for inborn errors of metabolism, she provided the following perspective: • Huge gaps in information and knowledge still exist because of a dearth of longitudinal follow-up to determine natural history in inherited metabolic diseases, and a lack of clinical trials.
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The current structure requires companies to file Investigational New Drug applications with FDA, which represents a risk for the companies. Falk said it is a real worry that medical foods, which patients rely on to maintain their lives and improve their health, are not being regulated properly and resulting in unnecessary deaths on occasion.
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2017. mino A acid medical foods provide a high dietary acid load and increase urinary xcretion e of renal net acid, calcium, and magnesium compared with glycomacropeptide medi cal foods in phenylketonuria.
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