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Austin R Long - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatographic analysis of vitamin k1in Medical Foods using matrix solid phase dispersion
Journal of Food Composition and Analysis, 2000Co-Authors: William G Chase, Ronald R. Eitenmiller, Austin R LongAbstract:Abstract A liquid chromatographic method for vitamin K 1 in Medical Foods is described. The vitamins are extracted from Medical food by matrix solid-phase dispersion (MSPD) and quantitated by reversed-phase chromatography with fluorescence detection. Vitamin K 1 is converted to the fluorescent hydroquinone with a post-column zinc reductive reactor. The limit of detection is 6.6 pg and the limit of quantitation is 22 pg on column. Linear response ranged from 45 to 908 pg on column ( r 2 =0.998). Recoveries were determined on an analyte-fortified zero control reference material (ZRM) for Medical Foods and averaged 97.9% ( n =25) for vitamin K 1 . The method provides a rapid, specific and easily controlled assay for the analysis of vitamin K 1 in fortified Medical Foods.
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determination of vitamin k1 in Medical Foods by liquid chromatography with postcolumn reduction and fluorometric detection
Journal of AOAC International, 2000Co-Authors: George M Ware, Ronald R. Eitenmiller, G W Chase, Austin R LongAbstract:A liquid chromatographic (LC) method is described for the determination of vitamin K1 in Medical Foods. The sample is enzymatically digested with lipase and alpha-amylase and extracted with 1% sodium bicarbonate solution-isopropanol (1 + 1). After C18 solid-phase extraction, vitamin K1 is separated by nonaqueous reversed-phase LC, converted to the hydroquinone by postcolumn zinc reduction, and quantitated by fluorescence detection. The limit of detection is 8 pg (3 sigma), and the limit of quantitation is 27 pg (10 sigma) on column. Linear response ranged from 0.1 to 1.0 ng vitamin K1 (r= 0.9999). The mean recovery (n = 38) for all spiking levels was 101.6 +/- 2.85%. Analysis of Standard Reference Material 1846, Infant Formula, gave a mean value of 0.95 +/- 0.088 mg vitamin K/kg (K or K1?) (n = 31) with a coefficient of variation of 9.26.
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Analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in Medical Foods using a zero control reference material (ZRM) as a method development tool.
Journal of AOAC International, 1999Co-Authors: Ronald R. Eitenmiller, Austin R LongAbstract:A liquid chromatographic method is described for analysis of all- rac-alpha-tocopheryl acetate and retinyl palmitate in Medical food. The vitamins are extracted in isopropyl alcohol and hexane-ethyl acetate without saponification and quantitated by normal-phase chromatography with fluorescence detection. All rac-alpha-tocopheryl acetate and retinyl palmitate are chromatographed isocratically with a mobile phase of 0.5% (v/v) and 0.125% (v/v) isopropyl alcohol in hexane, respectively. Recovery studies performed on a Medical food zero control reference material (ZRM) fortified with the analytes averaged 99.7% (n = 25) for retinyl palmitate and 101% (n = 25) for all- rac-alpha-tocopheryl acetate. Coefficients of variation were 0.87-2.63% for retinyl palmitate and 1.42-3.20% for all-rac-alpha-tocopheryl acetate. The method provides a rapid, specific, and easily controlled assay for analysis of vitamin A and vitamin E in Medical Foods. Use of chlorinated solvents is avoided.
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a liquid chromatographic method for analysis of all rac alpha tocopheryl acetate and retinyl palmitate in Medical food using matrix solid phase dispersion in conjunction with a zero reference material as a method development tool
Journal of AOAC International, 1999Co-Authors: G W Chase, Ronald R. Eitenmiller, Austin R LongAbstract:A liquid chromatographic method is described for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in Medical food. The vitamins are extracted from Medical food without saponification by matrix solid-phase dispersion and chromatographed by normal-phase chromatography with fluorescence detection. Retinyl palmitate and all-rac-alpha-tocopheryl acetate are quantitated isocratically with a mobile phase of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol in hexane, respectively. Results compared favorably with label declarations on retail Medical Foods. Recoveries determined on an analyte-fortified zero reference material for a milk-based Medical food averaged 98.3% (n = 25) for retinyl palmitate spikes and 95.7% (n = 25) for all-rac-alpha-tocopheryl acetate spikes. Five concentrations were examined for each analyte, and results were linear (r2 = 0.995 for retinyl palmitate and 0.9998 for all-rac-alpha-tocopheryl acetate) over the concentration range examined, with coefficients of variation in the range 0.81-4.22%. The method provides a rapid, specific, and easily controlled assay for analysis of retinyl palmitate and all-rac-alpha-tocopheryl acetate in fortified Medical Foods.
Denise M Ney - One of the best experts on this subject based on the ideXlab platform.
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Sex differences in body composition and bone mineral density in phenylketonuria: A cross-sectional study
Elsevier, 2018Co-Authors: Bridget M Stroup, Neil Binkley, Karen E Hansen, Diane Krueger, Denise M NeyAbstract:Background: Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). Objective: To determine if there are differences in BMD and body composition between male and female participants with PKU. Methods: From our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid Medical Foods (AA-MF) or glycomacropeptide Medical Foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15–50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16–35y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1–3weeks each. Results: Male participants had significantly lower mean total body BMD Z-scores (means±SE, males=−0.9±0.4; females, 0.2±0.3; p=0.01) and tended to have lower mean L1–4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above −1.0 compared to 100% of females (p=0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r=−0.58; p=0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means±SE, males: 67±6g, females: 52±4g; p=0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339±75mg/d, females: 228±69mg/d; p=0.13). Females had a greater percentage of total fat mass compared to males (means±SE, males: 24.5±4.8%, females: 36.5±2.5%; p=0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index. Conclusions: Males with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258. Keywords: Amino acid, Appendicular lean mass index, Glycomacropeptide, Medical food, Osteoporosis, Renal net acid, Trabecular bone score, Urinary calcium excretio
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metabolomic insights into the nutritional status of adults and adolescents with phenylketonuria consuming a low phenylalanine diet in combination with amino acid and glycomacropeptide Medical Foods
Journal of Nutrition and Metabolism, 2017Co-Authors: Bridget M Stroup, Denise M Ney, Sangita G Murali, Sandra C Van Calcar, Frances Rohr, Sally T Gleason, Harvey L LevyAbstract:Background. Nutrient status in phenylketonuria (PKU) requires surveillance due to the restrictive low-Phe diet in combination with amino acid Medical Foods (AA-MF) or glycomacropeptide Medical Foods (GMP-MF). Micronutrient profiles of Medical Foods are diverse, and optimal micronutrient supplementation in PKU has not been established. Methods. In a crossover design, 30 participants with PKU were randomized to consume AA-MF and Glytactin™ GMP-MF in combination with a low-Phe diet for 3 weeks each. Fasting venipunctures, Medical food logs, and 3-day food records were obtained. Metabolomic analyses were completed in plasma and urine by Metabolon, Inc. Results. The low-Phe diets in combination with AA-MF and GMP-MF were generally adequate based on Dietary Reference Intakes, clinical measures, and metabolomics. Without micronutrient supplementation of Medical Foods, >70% of participants would have inadequate intakes for 11 micronutrients. Despite micronutrient supplementation of Medical Foods, inadequate intakes of potassium in 93% of participants and choline in >40% and excessive intakes of sodium in >63% of participants and folic acid in >27% were observed. Sugar intake was excessive and provided 27% of energy. Conclusions. Nutrient status was similar with AA-MF and Glytactin GMP-MF. More research related to micronutrient supplementation of Medical Foods for the management of PKU is needed.
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dietary amino acid intakes associated with a low phenylalanine diet combined with amino acid Medical Foods and glycomacropeptide Medical Foods and neuropsychological outcomes in subjects with phenylketonuria
Data in Brief, 2017Co-Authors: Bridget M Stroup, Sangita G Murali, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L Levy, Denise M NeyAbstract:Abstract This article provides original data on median dietary intake of 18 amino acids from amino acid Medical Foods, glycomacropeptide Medical Foods, and natural Foods based on 3-day food records obtained from subjects with phenylketonuria who consumed low-phenylalanine diets in combination with amino acid Medical Foods and glycomacropeptide Medical Foods for 3 weeks each in a crossover design. The sample size of 30 subjects included 20 subjects with classical phenylketonuria and 10 with a milder or variant form of phenylketonuria. Results are presented for the Delis-Kaplan Executive Function System and the Cambridge Neuropsychological Test Automated Battery; the tests were administered at the end of each 3-week dietary treatment with amino acid Medical Foods and glycomacropeptide Medical Foods. The data are supplemental to our clinical trial, entitled “Glycomacropetide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial, 2016 (1) and “Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of Medical Foods in phenylketonuria, 2017 (2). This data has been made public and has utility to clinicians and researchers due to the following: 1) This provides the first comprehensive report of typical intakes of 18 amino acids from natural Foods, as well as amino acid and glycomacropeptide Medical Foods in adolescents and adults with phenylketonuria; and 2) This is the first evidence of similar standardized neuropsychological testing data in adolescents and adults with early-treated phenylketonuria who consumed amino acid and glycomacropeptide Medical Foods.
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metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of Medical Foods in phenylketonuria
Molecular Genetics and Metabolism, 2017Co-Authors: Denise M Ney, Sangita G Murali, Bridget M Stroup, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L LevyAbstract:Abstract Background Deficiencies of the monoamine neurotransmitters, such as dopamine synthesized from Tyr and serotonin synthesized from Trp, are of concern in PKU. Our objective was to utilize metabolomics analysis to assess monoamine metabolites in subjects with PKU consuming amino acid Medical Foods (AA-MF) and glycomacropeptide Medical Foods (GMP-MF). Methods Subjects with PKU consumed a low-Phe diet combined with AA-MF or GMP-MF for 3 weeks each in a randomized, controlled, crossover study. Metabolomic analysis was conducted by Metabolon, Inc. on plasma (n = 18) and urine (n = 9) samples. Catecholamines and 6-sulfatoxymelatonin were measured in 24-h urine samples. Results Intake of Tyr and Trp was ~ 50% higher with AA-MF, and AA-MF were consumed in larger quantities, less frequently during the day compared with GMP-MF. Performance on neuropsychological tests and concentrations of neurotransmitters derived from Tyr and Trp were not significantly different with AA-MF or GMP-MF. Plasma serotonin levels of gut origin were higher in subjects with variant compared with classical PKU, and with GMP-MF compared with AA-MF in subjects with variant PKU. Metabolomics analysis identified higher levels of microbiome-derived compounds synthesized from Tyr, such as phenol sulfate, and higher levels of compounds synthesized from Trp in the kynurenine pathway, such as quinolinic acid, with ingestion of AA-MF compared with GMP-MF. Conclusions The Tyr from AA-MF is less bioavailable due, in part, to greater degradation by intestinal microbes compared with the Tyr from prebiotic GMP-MF. Research is needed to understand how metabolism of Trp via the kynurenine pathway and changes in the intestinal microbiota affect health for individuals with PKU. This trial is registered at www.clinicaltrials.gov as NCT01428258 .
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designing Medical Foods for inherited metabolic disorders why intact protein is superior to amino acids
Current Opinion in Biotechnology, 2017Co-Authors: Denise M Ney, Mark R EtzelAbstract:Phenylketonuria and tyrosinemia are inherited metabolic disorders characterized by high blood levels of phenylalanine (Phe) or tyrosine (Tyr), due to mutations in genes affecting Phe and Tyr metabolism, respectively. The primary management is a lifelong diet restricted in protein from natural Foods in combination with Medical Foods comprised mixtures of synthetic amino acids. Compliance is often poor after childhood leading to neuropsychological sequela. Glycomacropeptide, an intact 64 amino acid glycophosphopeptide isolated from cheese whey, provides a new paradigm for the management of phenylketonuria and tyrosinemia because glycomacropeptide contains no Phe and Tyr in its pure form, and is also a prebiotic. Medical Foods made from glycomacropeptide have been used successfully for the management of phenylketonuria and tyrosinemia. Preclinical and clinical studies demonstrate that intact protein from glycomacropeptide provides a more acceptable and physiologic source of defined protein compared to amino acids in Medical Foods. For example, harmful gut bacteria were reduced, beneficial short chain fatty acids increased, renal workload decreased, protein utilization increased, and bone fragility decreased using intact protein versus amino acids. Advances in biotechnology will propel the transition from synthetic amino acids to intact proteins for the management of inherited metabolic disorders.
Charles P Venditti - One of the best experts on this subject based on the ideXlab platform.
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a critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of Medical Foods part 2 cobalamin c deficiency
Genetics in Medicine, 2016Co-Authors: Irini Manoli, Jennifer G Myles, Jennifer L Sloan, Nuria Carrillocarrasco, Eva Morava, Kevin A Strauss, Holmes Morton, Charles P VendittiAbstract:Cobalamin C (cblC) deficiency impairs the biosynthesis of 5′-deoxyadenosyl-adenosyl- and methyl-cobalamin, resulting in methylmalonic acidemia combined with hyperhomocysteinemia and hypomethioninemia. However, some patients with cblC deficiency are treated with Medical Foods, devoid of methionine and high in leucine content, that are formulated for patients with isolated propionate oxidative defects. We examined the effects of imbalanced branched-chain amino acid intake on growth outcomes in cblC-deficient patients. Dietary intake was correlated with biochemical, anthropometric, and body composition measurements and other disease parameters in a cohort of 28 patients with early-onset cblC deficiency. Protein-restricted diets were followed by 21% of the patients, whereas 32% received Medical Foods. Patients on protein-restricted diets had lower height-for-age z-score (P = 0.034), whereas patients consuming Medical Foods had lower head circumference Z-scores (P = 0.037), plasma methionine concentrations (P = 0.001), and predicted methionine influx through the blood–brain barrier Z-score (−1.29 vs. −0.0617; P = 0.007). The combination of age at diagnosis, a history of seizures, and the leucine-to-valine dietary intake ratio best predicted head circumference Z-score based on multiple regression modeling (R2 = 0.945). Patients with cblC deficiency treated with Medical Foods designed for isolated methylmalonic acidemia are at risk for iatrogenic methionine deficiency that could adversely affect brain growth and development. Genet Med 18 4, 396–404.
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a critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of Medical Foods part 1 isolated methylmalonic acidemias
Genetics in Medicine, 2016Co-Authors: Irini Manoli, Jennifer G Myles, Jennifer L Sloan, Oleg A Shchelochkov, Charles P VendittiAbstract:Medical Foods for methylmalonic acidemias (MMAs) and propionic acidemias contain minimal valine, isoleucine, methionine, and threonine but have been formulated with increased leucine. We aimed to assess the effects of imbalanced branched-chain amino acid intake on metabolic and growth parameters in a cohort of patients with MMA ascertained via a natural history study. Cross-sectional anthropometric and body-composition measurements were correlated with diet content and disease-related biomarkers in 61 patients with isolated MMA (46 mut, 9 cblA, and 6 cblB). Patients with MMA tolerated close to the recommended daily allowance (RDA) of complete protein (mut0: 99.45 ± 32.05% RDA). However, 85% received Medical Foods, in which the protein equivalent often exceeded complete protein intake (35%). Medical food consumption resulted in low plasma valine and isoleucine concentrations, prompting paradoxical supplementation with these propiogenic amino acids. Weight- and height-for-age z-scores correlated negatively with the leucine-to-valine intake ratio (r = −0.453; P = 0.014; R2 = 0.209 and r = −0.341; P = 0.05; R2 = 0.123, respectively). Increased leucine intake in patients with MMA resulted in iatrogenic amino acid deficiencies and was associated with adverse growth outcomes. Medical Foods for propionate oxidation disorders need to be redesigned and studied prospectively to ensure efficacy and safety. Genet Med 18 4, 386–395.
Ronald R. Eitenmiller - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatographic analysis of vitamin k1in Medical Foods using matrix solid phase dispersion
Journal of Food Composition and Analysis, 2000Co-Authors: William G Chase, Ronald R. Eitenmiller, Austin R LongAbstract:Abstract A liquid chromatographic method for vitamin K 1 in Medical Foods is described. The vitamins are extracted from Medical food by matrix solid-phase dispersion (MSPD) and quantitated by reversed-phase chromatography with fluorescence detection. Vitamin K 1 is converted to the fluorescent hydroquinone with a post-column zinc reductive reactor. The limit of detection is 6.6 pg and the limit of quantitation is 22 pg on column. Linear response ranged from 45 to 908 pg on column ( r 2 =0.998). Recoveries were determined on an analyte-fortified zero control reference material (ZRM) for Medical Foods and averaged 97.9% ( n =25) for vitamin K 1 . The method provides a rapid, specific and easily controlled assay for the analysis of vitamin K 1 in fortified Medical Foods.
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determination of vitamin k1 in Medical Foods by liquid chromatography with postcolumn reduction and fluorometric detection
Journal of AOAC International, 2000Co-Authors: George M Ware, Ronald R. Eitenmiller, G W Chase, Austin R LongAbstract:A liquid chromatographic (LC) method is described for the determination of vitamin K1 in Medical Foods. The sample is enzymatically digested with lipase and alpha-amylase and extracted with 1% sodium bicarbonate solution-isopropanol (1 + 1). After C18 solid-phase extraction, vitamin K1 is separated by nonaqueous reversed-phase LC, converted to the hydroquinone by postcolumn zinc reduction, and quantitated by fluorescence detection. The limit of detection is 8 pg (3 sigma), and the limit of quantitation is 27 pg (10 sigma) on column. Linear response ranged from 0.1 to 1.0 ng vitamin K1 (r= 0.9999). The mean recovery (n = 38) for all spiking levels was 101.6 +/- 2.85%. Analysis of Standard Reference Material 1846, Infant Formula, gave a mean value of 0.95 +/- 0.088 mg vitamin K/kg (K or K1?) (n = 31) with a coefficient of variation of 9.26.
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Analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in Medical Foods using a zero control reference material (ZRM) as a method development tool.
Journal of AOAC International, 1999Co-Authors: Ronald R. Eitenmiller, Austin R LongAbstract:A liquid chromatographic method is described for analysis of all- rac-alpha-tocopheryl acetate and retinyl palmitate in Medical food. The vitamins are extracted in isopropyl alcohol and hexane-ethyl acetate without saponification and quantitated by normal-phase chromatography with fluorescence detection. All rac-alpha-tocopheryl acetate and retinyl palmitate are chromatographed isocratically with a mobile phase of 0.5% (v/v) and 0.125% (v/v) isopropyl alcohol in hexane, respectively. Recovery studies performed on a Medical food zero control reference material (ZRM) fortified with the analytes averaged 99.7% (n = 25) for retinyl palmitate and 101% (n = 25) for all- rac-alpha-tocopheryl acetate. Coefficients of variation were 0.87-2.63% for retinyl palmitate and 1.42-3.20% for all-rac-alpha-tocopheryl acetate. The method provides a rapid, specific, and easily controlled assay for analysis of vitamin A and vitamin E in Medical Foods. Use of chlorinated solvents is avoided.
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a liquid chromatographic method for analysis of all rac alpha tocopheryl acetate and retinyl palmitate in Medical food using matrix solid phase dispersion in conjunction with a zero reference material as a method development tool
Journal of AOAC International, 1999Co-Authors: G W Chase, Ronald R. Eitenmiller, Austin R LongAbstract:A liquid chromatographic method is described for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in Medical food. The vitamins are extracted from Medical food without saponification by matrix solid-phase dispersion and chromatographed by normal-phase chromatography with fluorescence detection. Retinyl palmitate and all-rac-alpha-tocopheryl acetate are quantitated isocratically with a mobile phase of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol in hexane, respectively. Results compared favorably with label declarations on retail Medical Foods. Recoveries determined on an analyte-fortified zero reference material for a milk-based Medical food averaged 98.3% (n = 25) for retinyl palmitate spikes and 95.7% (n = 25) for all-rac-alpha-tocopheryl acetate spikes. Five concentrations were examined for each analyte, and results were linear (r2 = 0.995 for retinyl palmitate and 0.9998 for all-rac-alpha-tocopheryl acetate) over the concentration range examined, with coefficients of variation in the range 0.81-4.22%. The method provides a rapid, specific, and easily controlled assay for analysis of retinyl palmitate and all-rac-alpha-tocopheryl acetate in fortified Medical Foods.
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method modification for liquid chromatographic determination of thiamine riboflavin and pyridoxine in Medical Foods
Journal of AOAC International, 1993Co-Authors: G W Chase, William O Landen, A M Soliman, Ronald R. EitenmillerAbstract:A reversed-phased ion pair liquid chromatographic method developed for the simultaneous determination of thiamine (B1), riboflavin (B2), and pyridoxine (B6) in perchloric acid extracts of infant formulas was modified to include Medical Foods. UV detection of B1 and B2 was replaced by fluorescence detection, which resulted in improved sensitivity and specificity. B1 was detected by fluorescence after conversion to thiochrome by a postcolumn reaction with sodium hydroxide and potassium ferricyanide. The method uses a mobile phase of water, acetonitrile, hexanesulfonic acid sodium salt, ammonium hydroxide, and phosphoric acid adjusted to pH 3.6. The column is a 300 x 3.9 mm Nova Pak C18. Limits of detection were 0.05 microgram/mL for B1 and B2 and 0.01 microgram/mL for B6 by fluorescence detection. The system reproducibility was evaluated by completing 10 repetitive determinations on a Medical food that gave a coefficient of variation of 5.9, 6.0, and 10.7% for B1, B2, and B6, respectively. Mean recoveries (n = 10) were 111, 96.3, and 113% for B1, B2, and B6, respectively. The results compared favorably with those by AOAC Official Methods 942.23, 940.33, and 961.15 for B1, B2, and B6, respectively.
Irini Manoli - One of the best experts on this subject based on the ideXlab platform.
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a critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of Medical Foods part 2 cobalamin c deficiency
Genetics in Medicine, 2016Co-Authors: Irini Manoli, Jennifer G Myles, Jennifer L Sloan, Nuria Carrillocarrasco, Eva Morava, Kevin A Strauss, Holmes Morton, Charles P VendittiAbstract:Cobalamin C (cblC) deficiency impairs the biosynthesis of 5′-deoxyadenosyl-adenosyl- and methyl-cobalamin, resulting in methylmalonic acidemia combined with hyperhomocysteinemia and hypomethioninemia. However, some patients with cblC deficiency are treated with Medical Foods, devoid of methionine and high in leucine content, that are formulated for patients with isolated propionate oxidative defects. We examined the effects of imbalanced branched-chain amino acid intake on growth outcomes in cblC-deficient patients. Dietary intake was correlated with biochemical, anthropometric, and body composition measurements and other disease parameters in a cohort of 28 patients with early-onset cblC deficiency. Protein-restricted diets were followed by 21% of the patients, whereas 32% received Medical Foods. Patients on protein-restricted diets had lower height-for-age z-score (P = 0.034), whereas patients consuming Medical Foods had lower head circumference Z-scores (P = 0.037), plasma methionine concentrations (P = 0.001), and predicted methionine influx through the blood–brain barrier Z-score (−1.29 vs. −0.0617; P = 0.007). The combination of age at diagnosis, a history of seizures, and the leucine-to-valine dietary intake ratio best predicted head circumference Z-score based on multiple regression modeling (R2 = 0.945). Patients with cblC deficiency treated with Medical Foods designed for isolated methylmalonic acidemia are at risk for iatrogenic methionine deficiency that could adversely affect brain growth and development. Genet Med 18 4, 396–404.
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a critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of Medical Foods part 1 isolated methylmalonic acidemias
Genetics in Medicine, 2016Co-Authors: Irini Manoli, Jennifer G Myles, Jennifer L Sloan, Oleg A Shchelochkov, Charles P VendittiAbstract:Medical Foods for methylmalonic acidemias (MMAs) and propionic acidemias contain minimal valine, isoleucine, methionine, and threonine but have been formulated with increased leucine. We aimed to assess the effects of imbalanced branched-chain amino acid intake on metabolic and growth parameters in a cohort of patients with MMA ascertained via a natural history study. Cross-sectional anthropometric and body-composition measurements were correlated with diet content and disease-related biomarkers in 61 patients with isolated MMA (46 mut, 9 cblA, and 6 cblB). Patients with MMA tolerated close to the recommended daily allowance (RDA) of complete protein (mut0: 99.45 ± 32.05% RDA). However, 85% received Medical Foods, in which the protein equivalent often exceeded complete protein intake (35%). Medical food consumption resulted in low plasma valine and isoleucine concentrations, prompting paradoxical supplementation with these propiogenic amino acids. Weight- and height-for-age z-scores correlated negatively with the leucine-to-valine intake ratio (r = −0.453; P = 0.014; R2 = 0.209 and r = −0.341; P = 0.05; R2 = 0.123, respectively). Increased leucine intake in patients with MMA resulted in iatrogenic amino acid deficiencies and was associated with adverse growth outcomes. Medical Foods for propionate oxidation disorders need to be redesigned and studied prospectively to ensure efficacy and safety. Genet Med 18 4, 386–395.