Under-referral of Plain community members for genetic services despite being qualified for genetic evaluation.

Plain community people (Amish and Mennonites) have increased risk of having recessive genetic disorders. This study was designed to assess the rate of referral of Plain people to genetic services at UPMC Children's Hospital of Pittsburgh. Medical records of Plain patients from a 1-year time period were reviewed. Data collected included demographic information, clinical presentation, referral for genetic services, and diagnosis. Of the 303 patients, 102 (33.7%) had a clinical presentation suggestive of a genetic disorder, yet only 32 of those 102 patients (31.4%) had been evaluated by the division of Medical Genetics. These data indicate that less than half of Plain patients with a clinical presentation suggestive of a genetic disorder had been referred to the division of Medical Genetics for a formal evaluation. Now that under-referral of Plain patients has been confirmed, providers can be educated in order to increase referrals for genetic services and facilitate positive healthcare outcomes for the Plain Community.

5-year retrospective analysis of patients with phenylketonuria (PKU) and hyperphenylalaninemia treated at two specialized clinics.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease caused by mutations in the PAH gene, resulting in deficiency of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine (Phe) to tyrosine (Tyr). The purpose of this study was to capture real-world data associated with managing PKU under current standard of care and to characterize a representative population for a planned gene therapy trial. METHODS: A retrospective chart review was conducted at two U.S. clinics for individuals 10-40 years old diagnosed with PKU-related hyperphenylalaninemia (HPA). Demographics, medical history, treatments and blood Phe data were collected from electronic medical records spanning a five-year period ending in November 2017. RESULTS: 152 patients were enrolled (65.8% had classical PKU). Although >95% of patients were prescribed a Phe-restricted diet, blood Phe concentrations remained substantially elevated, particularly in patients diagnosed with classical PKU. As the Phe threshold was lowered (Phe < 600, 360, 120 or 30 µmol/L), the number of patients with consecutive lab values below the threshold decreased, suggesting that many patients' Phe levels are inadequately controlled. 62.5% of patients were reported as having a history of at least one neuropsychiatric comorbidity, and adults were more likely than adolescents (69.5% vs. 54.3%). 92 of 98 PAH genotypes collected were distinct mutations; the 6 null-null genotypes were associated with classical PKU. Overall the demographics and clinical data were consistent across both sites. CONCLUSION: Despite dietary restrictions, mean Phe concentrations were > 360 µmol/L (a level considered well-controlled based on current U.S. treatment guidelines) for mild, moderate, and classical PKU patients. There remains an unmet need for therapies to control Phe concentrations.