Recommendations for the nutrition management of phenylalanine hydroxylase deficiency

The effectiveness of a phenylalanine-restricted diet to improve the outcome of individuals with phenylalanine hydroxylase deficiency (OMIM no. 261600) has been recognized since the first patients were treated 60 years ago. However, the treatment regime is complex, costly, and often difficult to maintain for the long term. Improvements and refinements in the diet for phenylalanine hydroxylase deficiency have been made over the years, and adjunctive therapies have proven to be successful for certain patients. Yet evidence-based guidelines for managing phenylalanine hydroxylase deficiency, optimizing outcomes, and addressing all available therapies are lacking. Thus, recommendations for nutrition management were developed using evidence from peer-reviewed publications, gray literature, and consensus surveys. The areas investigated included choice of appropriate medical foods, integration of adjunctive therapies, treatment during pregnancy, monitoring of nutritional and clinical markers, prevention of nutrient deficiencies, providing of access to care, and compliance strategies. This process has not only provided assessment and refinement of current nutrition management and monitoring recommendations but also charted a direction for future studies. This document serves as a companion to the concurrently published American College of Medical Genetics and Genomics guideline for the medical treatment of phenylalanine hydroxylase deficiency

Rhabdomyolysis in a neonate due to very long chain acyl CoA dehydrogenase deficiency

Very long chain acyl CoA dehydrogenase deficiency (VLCADD) is an inborn error in long chain fatty acid oxidation with significant variability in the severity and timing of its clinical presentation. Neonatal presentations of VLCADD have included hypoglycemia and cardiomyopathy while rhabdomyolysis is usually a later onset complication. We describe a neonate with VLCADD presenting with rhabdomyolysis prior to the return of an abnormal newborn screen. This report suggests that evaluating for rhabdomyolysis, in addition to a cardiac and hepatic work-up, is an important part of the initial evaluation of an infant with an abnormal newborn screen suggesting a diagnosis of VLCADD

Successful pregnancy and delivery in a woman with propionic acidemia from the Amish community

Propionic acidemia (PA) is an inborn error of protein metabolism with a variable clinical presentation ranging from neonatal encephalopathy to seemingly asymptomatic individuals who present with cardiomyopathy or sudden death. PA is recognized in the Amish population, often with an early asymptomatic course and eventual cardiac complications. Thus, Amish women with PA may reach reproductive age without clinical sequelae, but are at increased risk for metabolic decompensation during pregnancy, delivery and postpartum period. We describe the care of an Amish woman with PA during her first pregnancy and delivery

The Effect of Preoperative Carbohydrate Intake on Length of Stay and Postoperative Recovery Following Laparoscopic Living Donor Nephrectomy.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) protocols are applied in many surgical procedures and often involve preoperative carbohydrate intake. Research surrounding the utility of ERAS in living donor nephrectomy is limited. The objective of this study was to identify whether living kidney donors who received preoperative oral carbohydrates experienced a difference in length of hospital stay (LOS), duration of time required to resume regular oral food and fluid intake, and incidence of gastrointestinal (GI) complications following laparoscopic nephrectomy compared to historical control donors who underwent preoperative fasting. METHODS: This study was a retrospective analysis of data from adult subjects at one transplant center who underwent laparoscopic living donor nephrectomy. A total of 55 ERAS subjects who received preoperative carbohydrates and 93 historical control subjects who underwent preoperative fasting were included in the final analysis. The following variables were compared between groups: LOS, time to tolerating a regular oral diet postoperatively, time to meeting 50% of estimated fluid needs by oral intake postoperatively, and incidence of postoperative GI complications. RESULTS: No significant differences between the ERAS and historical control groups in age, weight, body mass index, sex distribution, or estimated fluid needs were identified. Both groups consisted of predominantly female subjects. ERAS subjects experienced a shorter LOS (2.8 days versus 3.9 days, P \u3c .001), time to tolerating a regular oral diet (36.5 hours versus 68.2 hours, P \u3c .001), and time to meeting 50% of estimated fluid needs (25.3 hours versus 44.6 hours, P \u3c .001) after laparoscopic nephrectomy compared to historical control subjects. No significant difference between groups in the incidence of postoperative GI complications (nausea, vomiting, or ileus) was identified. CONCLUSION: Our findings demonstrate the advantages of ERAS in living kidney donors undergoing laparoscopic nephrectomy and support ERAS implementation within this patient population

The efficacy of Carbamylglutamate impacts the nutritional management of patients with N-Acetylglutamate synthase deficiency

Abstract Background The autosomal recessive disorder N-acetylglutamate synthase (NAGS) deficiency is the rarest defect of the urea cycle, with an incidence of less than one in 2,000,000 live births. Hyperammonemic crises can be avoided in individuals with NAGS deficiency by the administration of carbamylglutamate (also known as carglumic acid), which activates carbamoyl phosphatase synthetase 1 (CPS1). The aim of this case series was to introduce additional cases of NAGS deficiency to the literature as well as to assess the role of nutrition management in conjunction with carbamylglutamate therapy across new and existing cases. Methods We conducted retrospective chart reviews of seven cases of NAGS deficiency in the US and Canada, focusing on presentation, diagnosis, medication management, nutrition management, and outcomes. Results Five new and two previously published cases were included. Presenting symptoms were consistent with previous reports. Diagnostic confirmation via molecular testing varied in protocol across cases, with consecutive single gene tests leading to long delays in diagnosis in some cases. All patients responded well to carbamylglutamate therapy, as indicated by normalization of plasma ammonia and citrulline, as well as urine orotic acid in patients with abnormal levels at baseline. Although protein restriction was not prescribed in any cases after carbamylglutamate initiation, two patients continued to self-restrict protein intake. One patient experienced two episodes of hyperammonemia that resulted in poor long-term outcomes. Both episodes occurred after a disruption in access to carbamylglutamate, once due to insurance prior authorization requirements and language barriers and once due to seizure activity limiting the family’s ability to administer carbamylglutamate. Conclusions Follow-up of patients with NAGS deficiency should include plans for illness and for disruption of carbamylglutamate access, including nutrition management strategies such as protein restriction. Carbamylglutamate can help patients with NAGS deficiency to liberalize their diets, but the maximum safe level of protein intake to prevent hyperammonemia is not yet known. Patients using this medication should still monitor their diet closely and be prepared for any disruptions in medication access, which might require immediate dietary adjustments or medical intervention to prevent hyperammonemia

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

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