Inconsistencies in the Nutrition Management of Glutaric Aciduria Type 1: An International Survey

Glutaric aciduria type 1 (GA-1) is a cerebral organic aciduria characterized by striatal injury and progressive movement disorder. Nutrition management shifted from a general restriction of intact protein to targeted restriction of lysine and tryptophan. Recent guidelines advocate for a low-lysine diet using lysine-free, tryptophan-reduced medical foods. GA-1 guideline recommendations for dietary management of patients over the age of six are unclear, ranging from avoiding excessive intake of intact protein to counting milligrams of lysine intake. A 22–question survey on the nutrition management of GA-1 was developed with the goal of understanding approaches to diet management for patients identified by newborn screening under age six years compared to management after diet liberalization, as well as to gain insight into how clinicians define diet liberalization. Seventy-six responses (25% of possible responses) to the survey were received. Nutrition management with GA-1 is divergent among surveyed clinicians. There was congruency among survey responses to the guidelines, but there is still uncertainty about how to counsel patients on diet optimization and when diet liberalization should occur. Ongoing clinical research and better understanding of the natural history of this disease will help establish stronger recommendations from which clinicians can best counsel families

Nutritional Therapy Improves Growth and Protein Status of Children with a Urea Cycle Enzyme Defect

Background Poor growth has been described in patients with urea cycle enzyme defects treated with protein-restricted diets, while protein status is seldom reported. Objective To assess the effects of nutritional therapy with a medical food on growth and protein status of patients with a urea cycle enzyme defect. Methods A 6-mo multicenter outpatient study was conducted with infants and toddlers managed by nutrition therapy with Cyclinex-1 Amino Acid-Modified Medical Food with Iron (Ross Products Division, Abbott Laboratories, Columbus, OH). Main outcome variables were anthropometrics and plasma amino acids (selected), albumin, and transthyretin concentrations. Results Seventeen patients completed the study. Mean (±SE) baseline age was 11.30 ± 3.20 months (median 4.40 months; range 0.22–38.84 months). Length and weight z-scores increased significantly during the 6-month study. Head circumference increased, but not significantly. Three patients were stunted and two were wasted (−2.0 z-score) at baseline while at study end, only one patient was both stunted and wasted. The majority of patients increased in length, head circumference, and weight z-scores during study. Mean (±SE) plasma albumin concentration increased from 34 ± 2 g/L at baseline to 38 ± 1 g/L at study end. Plasma transthyretin increased from a mean (±SE) of 177 ± 13 mg/L at baseline to 231 ± 15 mg/L at study end. No correlation was found between plasma NH3 concentrations and medical food intake. Plasma NH3concentration was positively correlated with the percentage of Food and Agriculture Organization/World Health Organization/United Nations recommended protein ingested. Conclusions Intakes of adequate protein and energy for age result in anabolism and linear growth without increasing plasma NH3 concentrations. Medical food intakes did not correlate with plasma NH3 concentrations

Nutritional Therapy Improves Growth and Protein Status of Children with a Urea Cycle Enzyme Defect

Background Poor growth has been described in patients with urea cycle enzyme defects treated with protein-restricted diets, while protein status is seldom reported. Objective To assess the effects of nutritional therapy with a medical food on growth and protein status of patients with a urea cycle enzyme defect. Methods A 6-mo multicenter outpatient study was conducted with infants and toddlers managed by nutrition therapy with Cyclinex-1 Amino Acid-Modified Medical Food with Iron (Ross Products Division, Abbott Laboratories, Columbus, OH). Main outcome variables were anthropometrics and plasma amino acids (selected), albumin, and transthyretin concentrations. Results Seventeen patients completed the study. Mean (±SE) baseline age was 11.30 ± 3.20 months (median 4.40 months; range 0.22–38.84 months). Length and weight z-scores increased significantly during the 6-month study. Head circumference increased, but not significantly. Three patients were stunted and two were wasted (−2.0 z-score) at baseline while at study end, only one patient was both stunted and wasted. The majority of patients increased in length, head circumference, and weight z-scores during study. Mean (±SE) plasma albumin concentration increased from 34 ± 2 g/L at baseline to 38 ± 1 g/L at study end. Plasma transthyretin increased from a mean (±SE) of 177 ± 13 mg/L at baseline to 231 ± 15 mg/L at study end. No correlation was found between plasma NH3 concentrations and medical food intake. Plasma NH3concentration was positively correlated with the percentage of Food and Agriculture Organization/World Health Organization/United Nations recommended protein ingested. Conclusions Intakes of adequate protein and energy for age result in anabolism and linear growth without increasing plasma NH3 concentrations. Medical food intakes did not correlate with plasma NH3 concentrations

Improved Growth and Nutrition Status in Children with Methylmalonic or Propionic Acidemia Fed an Elemental Medical Food

Background: Failure-to-thrive (FTT) has been described in patients with organic acidemias treated with low protein diets. Objective: To determine if patients with methylmalonic (MMA) or propionic acidemia (PA) can achieve normal growth and nutrition status. Methods: A 6-month multicenter outpatient study was conducted with infants and toddlers treated with Propimex-1 Amino Acid-Modified Medical Food With Iron (Ross Products Division, Abbott Laboratories, Columbus, OH). Main outcome measures were anthropometrics, protein status indices, plasma retinol, and α-tocopherol. Results: Sixteen patients completed the study. Mean baseline age was 0.54 ± 0.02 years (range 0.03–3.00 years). By study end, mean National Center for Health Statistics (NCHS) weight centile increased from 26 to 49%; mean crown-heel length centile from 25 to 33%; and mean head circumference centile from 43 to 54%. Mean (± SE) protein and energy intakes by \u3c6-month-old, 6 \u3c 12-month-old, and 1\u3c 4-year-old patients were 15.3 ± 0.9 g and 645 ± 10 kcal; 18.3 ± 1.1 g and 741 ± 92 kcal; and 25.1 ± 2.46 g and 1062 ± 100 kcal, respectively. Plasma glycine concentrations were significantly and negatively correlated with energy intake (r=−0.77, p\u3c0.0005). No correlation was found between dietary protein intakes and plasma ammonia concentrations. Protein status indices, retinol and α-tocopherol concentrations were within reference ranges at study end. Conclusions: Propimex-1 improved growth and nutrition status in patients with MMA or PA in just 6 months when fed in sufficient amounts. Providing energy and protein for patients with FTT at intakes recommended for catch-up growth may have resulted in even better growth

Phenylketonuria Scientific Review Conference:State of the science and future research needs

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 Rtnol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 [tmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.</p