Primary care physicians (PCPs) are considered the gatekeepers of genetic services, but they often underutilize or inappropriately utilize such services, leading to lack of early treatment, incorrect diagnoses, and unnecessary procedures. This study aims to delineate PCP referral patterns, including the frequency of, motivators for, and barriers to genetic referrals and testing in the present landscape of genomics. A 34-item online survey was distributed to PCPs in the United States (US). PCP demographics, practice characteristics, and referral patterns, motivators, and barriers were analyzed. Six hypothetical clinical scenarios included in the survey also were presented to a cohort of clinical geneticists. We calculated PCPs’ rates of ordering genetic tests and of referral to genetics services in the past year. Rates and responses to clinical scenarios were compared based on respondents’ personal and practice characteristics. A total of 95 PCPs and 25 clinical geneticists participated. Among the PCPs, 79% reported referring and 50% reported ordering genetic testing in the last year. PCPs with genetic counselors (GCs) in their clinic referred at significantly higher rates than those without (P = .008). White PCPs referred at significantly higher rates compared to Black or African American PCPs (P = .009). The most commonly reported motivators for referring patients to genetic services were preference for specialist coordination, lack of knowledge, and family’s desire for risk information. The most commonly reported barriers were patient refusal, provider concerns about costs to patients, and uncertainty of when a genetic referral is appropriate. In response to clinical scenarios, clinical geneticists were in agreement about the need for genetic testing or referral for 2 of the scenarios. For these 2 scenarios, only 48% and 71% of PCPs indicated that they would offer genetic testing or referral, respectively. Responses to clinical scenarios suggest that it is not clear to PCPs when referrals or testing are needed. Collaboration with GCs is one approach to reducing barriers to and improving PCPs’ utilization of genetic services. Clear guidelines from clinical geneticists may help facilitate appropriate use of genetics services by PCPs. Additional research is needed to further describe barriers that PCPs face in genetic testing/referrals.

Phenylalanine hydroxylase deficiency, or phenylketonuria (PKU), is a rare autosomal recessive metabolic disorder. Early diagnosis via newborn screening (NBS) and initiation of treatment prevent the development of cognitive impairment and other co-morbidities. The purpose of this study is to describe the natural history of PKU in the United States, including prevalence of co-morbidities and predictors of outcomes. We analyzed data from a self-report survey in the NBS-PKU Connect online registry. We describe the participants' nutrition management strategies, barriers to management, outcomes of bone disorders, skin, and psychological co-morbidities, and the use of special education or other special services. Predictors of outcomes were identified and assessed, including the impact of sex, age, age at diagnosis, blood phenylalanine concentration, use of sapropterin, use of medical food, adherence to prescribed diet, use of low protein modified foods, whether they had ever been off-diet, and use of tyrosine supplementation. The 219 respondents included individuals with PKU or hyperphenylalanemia (n = 78), or their caregivers (n = 141). Most (84.3%) started treatment before the age of two weeks. About one-third indicated that they had been off-diet at some point in their lives, and 81.4% reported that they currently adhered to their prescribed diet, with adherence to prescribed diet decreasing with age. Blood phenylalanine concentration was under the recommended threshold of 360 μmol/L for 68.5% of participants. One-quarter of respondents reported psychological co-morbidities, with anxiety and ADD/ADHD being the most common. The incidence of psychological co-morbidities increased with age and with ever having been off diet. Special education or other special services were more likely to be reported by individuals who were diagnosed after one week of age. Skin disorders such as acne and eczema were more common in females than males, and a minority of participants reported bone disorders. Despite recommendations to maintain blood phenylalanine concentrations in the therapeutic range throughout life, it is not uncommon for adults with PKU to discontinue dietary management of their disorder. Early diagnosis was associated with reduced need for special education or other special services, and continuous treatment was associated with decreased psychological co-morbidities.

Introduction/Objectives: Collectively, genetic diseases are not that rare, and with increasing availability of genetics-informed healthcare management, primary care providers (PCPs) are more often asked to screen for or provide genetic services. Previous studies have identified barriers that impact PCPs’ ability to provide genetic services, including limited knowledge, training, and time/resources. This study set out to identify specific barriers limiting genetics service provision by PCPs within the Southeastern Regional Genetics Network (SERN) and resources that would help eliminate those barriers. Methods: PCPs were recruited through provider networks and invited to participate in semi-structured interviews, conducted via Zoom, recorded, and transcribed verbatim. Interview transcripts were independently coded by 2 coders using MAXQDA software. Thematic analysis was conducted. Results: Eleven interviews were conducted. Three predominant themes emerged from the data regarding factors impacting use of genetic services: system-wide factors, provider-specific factors, and patient factors. System-wide barriers included a lack of genetics providers and logistic challenges, which led to some PCPs coordinating referrals with other specialists or independently managing patients. Regarding provider-specific barriers, PCPs reported lack of genetics knowledge making referrals challenging. When possible, many PCPs contacted genetics providers for assistance. When not possible, some PCPs reached out to other colleagues or specialists for guidance. Patient-specific barriers included concerns or lack of information regarding genetics and unmet social needs. Many PCPs provided additional education regarding genetics appointments or testing benefits to their patients. Assistance from genetic counselors, electronic medical record systems that support referral to genetics, prior experience referring to genetics, established communication channels with genetics professionals, and highly motivated patients all facilitated improved collaboration with genetic services. PCPs provided suggestions for future resources to support interactions with genetics, including clear referral guidelines, increased access to genetics providers, improved test ordering processes, increased access to genetic education, and communication systems. Conclusions: PCPs face barriers at 3 different levels when engaging with genetic services: systems, providers, and patients. This study identified strategies that PCPs use to address these barriers, which are dependent on individual resources and practice settings. These strategies demonstrate resourcefulness in working to incorporate genetics into clinics operating at maximum capacity. By targeting barriers that uniquely impact providers, systems, and patients, as well as building upon strategies that PCPs are already using, medical providers can support PCPs to help with the provision of genetic services.

Background: N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management. Methods: Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers. Results: In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported. Conclusions: Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate.

Breast milk is considered the optimal first food for infants. Breastfeeding infants with inherited metabolic disorders (IMDs) is complex due to the critical need to manage intake of specific macronutrients depending on the type of IMD. To describe current practices of registered dietitians (RD) who treat patients with IMDs regarding the incorporation of breastmilk into disease management. Cross-sectional survey. Participants/setting: online survey conducted in December 2020 of 66 RDs who treat patients with IMDs in the United States and Canada. Main outcome measures: the survey focused on personal demographics, clinic characteristics, institutional feeding protocols for infants with IMDs, confidence in working with breastfeeding parents of infants with IMDs, and knowledge about breastfeeding with questions derived from the Iowa Infant Feeding Attitudes Scale. Statistical analysis performed:. Fisher's exact test was used for comparisons. Most RDs were confident or very confident in their ability to provide nutritional guidance for breastfeeding infants with IMDs. Half of the participants reported that they had received training on breastfeeding of infants of IMDs. For infants with phenylketonuria (PKU), most RDs include breastfeeding as part of nutritional management. Breastfeeding is less likely to be used in the management of infants with other aminoacidopathies and fatty acid oxidation disorders. Use of measured expressed breastmilk was preferred, including for aminoacidopathies other than PKU, organic acidemias, and fatty acid oxidation disorders. Knowledge about breastfeeding varied. Less than half of RDs referred mothers to a lactation specialist somewhat regularly or frequently. Our survey found variation in experience, training, and use of breastfeeding-related nutritional management protocols in IMDs. A lack of formal training programs for the nutritional management of IMDs may account for some of this variation. Future research, including the collection of more detailed disorder-specific data, could help contribute to the development of clinical practice guidelines.