REVIEW: Practical strategies to maintain anabolism by intravenous nutritional management in children with inborn metabolic diseases.

One of the most vital elements of management for patients with inborn errors of intermediary metabolism is the promotion of anabolism, the state in which the body builds new components, and avoidance of catabolism, the state in which the body breaks down its own stores for energy. Anabolism is maintained through the provision of a sufficient supply of substrates for energy, as well as critical building blocks of essential amino acids, essential fatty acids, and vitamins for synthetic function and growth. Patients with metabolic diseases are at risk for decompensation during prolonged fasting, which often occurs during illnesses in which enteral intake is compromised. During these times, intravenous nutrition must be supplied to fully meet the specific nutritional needs of the patient. We detail our approach to intravenous management for metabolic patients and its underlying rationale. This generally entails a combination of intravenous glucose and lipid as well as early introduction of protein and essential vitamins. We exemplify the utility of our approach in case studies, as well as scenarios and specific disorders which require a more careful administration of nutritional substrates or a modification of macronutrient ratios.

Impact on Isoleucine and Valine Supplementation When Decreasing Use of Medical Food in the Nutritional Management of Methylmalonic Acidemia.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder treated with precursor-free medical food while limiting natural protein. This retrospective chart review was to determine if there was a relationship between medical food, valine (VAL) and/or isoleucine (ILE) supplementation, total protein intake, and plasma amino acid profiles. Methods: A chart review, of patients aged 31 days or older with MMA treated with dietary intervention and supplementation of VAL and/or ILE and followed at the Children's Hospital Colorado Inherited Metabolic Diseases Clinic. Dietary prescriptions and plasma amino acid concentrations were obtained at multiple time points. RESULTS: Baseline mean total protein intake for five patients was 198% of Recommended Dietary Allowance (RDA) with 107% natural protein and 91% medical food. Following intervention, total protein intake (p = 0.0357), protein from medical food (p = 0.0142), and leucine (LEU) from medical food (p = 0.0276) were lower, with no significant change in natural protein intake (p = 0.2036). At baseline, 80% of patients received VAL supplementation and 100% received ILE supplementation. After intervention, only one of the cohort remained on supplementation. There was no statistically significant difference in plasma propiogenic amino acid concentrations. CONCLUSIONS: Decreased intake of LEU from medical food allowed for discontinuation of amino acid supplementation, while meeting the RDA for protein.

Developing a circumpolar programme for the monitoring of Arctic terrestrial biodiversity.

The Arctic is undergoing biological and environmental changes, and a coordinated effort to monitor is critical to detect these changes. The Circumpolar Biodiversity Monitoring Programme (CBMP) of the Arctic Council biodiversity working group, Conservation of Arctic Flora and Fauna (CAFF), has developed pan-Arctic biodiversity monitoring plans that aims to improve the ability to detect and report on long-term changes. Whilst introducing this special issue, this paper also presents the making of the terrestrial monitoring plan and discusses how the plan follows the steps required for an adaptive and ecosystem-based monitoring programme. In this article, we discuss how data on key findings can be used to inform circumpolar and global assessments, including the State of the Arctic Terrestrial Biodiversity Report, which will be the first terrestrial assessment made by the CBMP. Key findings, advice for future monitoring and lessons learned will be used in planning next steps of pan-Arctic coordinated monitoring.

Multiclinic Observations on the Simplified Diet in PKU.

Phenylketonuria is an inborn error of metabolism that historically has been treated with a strict phenylalanine-restricted diet where all foods are weighed and measured. This is cumbersome and difficult for patients and caregivers, especially patients with high phenylalanine blood concentrations who often have neurocognitive deficits. The Simplified Diet is an alternative approach that allows for increased flexibility, promotes healthy food choices, and is easier to manage than a traditional diet for PKU. This paper describes the implementation of the Simplified Diet and outlines education, counseling strategies, and challenges encountered by three metabolic clinics in the United States.

Neurodevelopmental Outcome and Treatment Efficacy of Benzoate and Dextromethorphan in Siblings with Attenuated Nonketotic Hyperglycinemia.

OBJECTIVE: To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. STUDY DESIGN: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. RESULTS: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. CONCLUSIONS: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.

Triple therapy with pyridoxine, arginine supplementation and dietary lysine restriction in pyridoxine-dependent epilepsy: Neurodevelopmental outcome.

Pyridoxine-dependent epilepsy (PDE) is an epileptic encephalopathy characterized by response to pharmacologic doses of pyridoxine. PDE is caused by deficiency of α-aminoadipic semialdehyde dehydrogenase resulting in impaired lysine degradation and subsequent accumulation of α-aminoadipic semialdehyde. Despite adequate seizure control with pyridoxine monotherapy, 75% of individuals with PDE have significant developmental delay and intellectual disability. We describe a new combined therapeutic approach to reduce putative toxic metabolites from impaired lysine metabolism. This approach utilizes pyridoxine, a lysine-restricted diet to limit the substrate that leads to neurotoxic metabolite accumulation and L-arginine to compete for brain lysine influx and liver mitochondrial import. We report the developmental and biochemical outcome of six subjects who were treated with this triple therapy. Triple therapy reduced CSF, plasma, and urine biomarkers associated with neurotoxicity in PDE. The addition of arginine supplementation to children already treated with dietary lysine restriction and pyridoxine further reduced toxic metabolites, and in some subjects appeared to improve neurodevelopmental outcome. Dietary lysine restriction was associated with improved seizure control in one subject, and the addition of arginine supplementation increased the objective motor outcome scale in two twin siblings, illustrating the contribution of each component of this treatment combination. Optimal results were noted in the individual treated with triple therapy early in the course of the disease. Residual disease symptoms could be related to early injury suggested by initial MR imaging prior to initiation of treatment or from severe epilepsy prior to diagnosis. This observational study reports the use of triple therapy, which combines three effective components in this rare condition, and suggests that early diagnosis and treatment with this new triple therapy may ameliorate the cognitive impairment in PDE.

Geographic Variation in Zygomaxillary Suture Morphology and its Use in Ancestry Estimation.

Angled/curved zygomaxillary suture coding is widely employed in cranial assessments of ancestry. However, the efficacy of this method has not been extensively evaluated across diverse populations. In this study, zygomaxillary suture morphology was assessed on a total of 411 human crania from six populations (European, Native American, African, Asian, Arctic Circle, and Aboriginal Australian) using a novel 3D coordinate landmark method. Our results indicate a predominance of angled sutures among native peoples of the Arctic and North America (85-86%), a prevalence of curved sutures among Africans and Aboriginal Australians (77-81%), and essentially equal proportions of both configurations in Asians and Europeans (50-56%). Statistically, angled/curved coding generally discriminates poorly between groups, except when populations with antithetically high frequencies of the two configurations (e.g., African vs. Native American) are compared. Moreover, comparisons across previous studies reveal conflicting frequencies for many populations, further suggesting limited utility of this trait in ancestry estimation.