No abstract

Phenylketonuria (PKU) is an inherited disorder of phenylalanine (Phe) metabolism. Until recently, the only treatment for PKU was a Phe-restricted diet. Increasing evidence of suboptimal outcomes in diet-treated individuals, inconsistent PKU management practices, and the recent availability of tetrahydrobiopterin (BH(4)) therapy have fueled the need for new management and treatment recommendations for this metabolic disorder. BH(4), now available as sapropterin dihydrochloride (sapropterin), may offer the potential for improved metabolic control as well as enhanced dietary Phe tolerance in some PKU patients. A group of metabolic dietitians from North America convened in June 2011 to draft recommendations for the use of sapropterin therapy in PKU. Physicians with extensive experience in PKU management were invited at a later date to contribute to the development of these recommendations. Based on extensive clinical experience and current evidence, the present recommendations provide guidance from patient selection and determination of sapropterin response to the long-term management of patients on sapropterin therapy. Target Phe levels, nutritional adequacy, neurocognitive screening and adherence to treatment are addressed to optimize patient outcomes.

The dietary treatment of phenylketonuria (PKU) is a success story. However, the Maternal PKU Collaborative Study reported microcephaly, congenital heart defects, facial dysmorphology, and intrauterine and postnatal growth retardation in the offspring of women with blood phenylalanine (phe) concentrations >600 µmol/L. Dietary control of phe during pregnancy is extremely difficult for many women because of hyperemesis gravidarum, intolerance of the medical food products, and inability/ refusal to follow dietary recommendations. The authors report 2 case studies using 6R-BH4 along with the pherestricted diet. Two individuals received 6R-BH4 shortly before conception and throughout the pregnancy. A pherestricted diet was followed with blood phe analysis obtained weekly. Interim plasma amino acids, complete metabolic panels, complete blood counts, and analyses for nutritional deficiencies were also obtained during the pregnancy. Both individuals maintained blood phe concentrations within the recommended range (120-360 µmol/L) nearly all through the pregnancy with a small percentage outside of recommendations. One participant showed deficiencies in vitamin D and zinc and received supplementation. Both were able to increase natural protein as the pregnancy progressed. Ingestion of the 6R-BH4 was well tolerated. Both gave birth to healthy normal infants. In these case studies, both babies' birth measurements were in the normal range, and the 6R-BH4 had no adverse effects.

Introduction:Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle, has a variable phenotype, and is caused by mutations in the OTC gene. We report three cases of ornithine transcarbamylase deficiency to illustrate the late-onset presentation of this disorder and provide strategies for diagnosis and treatment. The patients were maternal first cousins, presenting with hyperammonemia and obtundation. Urea cycle disorder was not initially suspected in the first patient, delaying diagnosis.Results:Sequencing of the OTC gene showed a novel missense mutation, c.563G > C (p.G188A). Numerous family members were found to carry this mutation, which shows a trend toward later onset. Each urea cycle disorder has its own unique pattern of biochemical abnormalities, which differ from non-metabolic causes of critical illness.Conclusion:Regardless of age, clinical suspicion of a urea cycle disorder is important in encephalopathic patients to ensure quick diagnosis and definitive treatment of the underlying inborn error of metabolism.