FROM NEWBORN SCREENING TO OUTCOME EVALUATION: EXPERIENCE, CHALLENGES, AND OPPORTUNITIES FOR LONG TERM FOLLOW-UP OF METABOLIC DISORDERS. Botto LD 1 , Nabukera S 2 , Palmer M 1 , Piper K 3 , Feldkamp ML 1 , Romitti PA 2 1 Div Med Genet, Dpt Ped, Univ Utah, Salt Lake City, United States 2 Univ of Iowa, Iowa City, United States 3 Iowa Dpt Public Health, Iowa City, United States Background: Systematic collection of outcome data and public health benefits after expanded newborn screening is urgently needed, but scarce. One option is to enhance infrastructures of existing population-based birth defect surveillance programs. Methods: We expanded two such programs in the US (Utah and Iowa) to conduct surveillance for 19 selected metabolic conditions diagnosed by MS-MS. We developed case definitions and data dictionaries to track diagnoses, treatment, morbidity, mortality, and services used. Metabolic physicians assisted in case review. Results: The two-state cohort included 52 affected infants (cases) from among 229,353 live births delivered from 2005-2007. MCAD, PKU, and 3MCC accounted for 46 cases. Most cases had follow-up through age 2 years. 3MCC accounted for one-fifth of cases but one-half of those lost to follow-up. By age 2, one-fourth of children had an emergency room visit and one-third a hospitalization; such visits and hospitalizations decreased after age 1 year. Overall mortality was low (n=1, VLCAD deficiency). In terms of workload, these metabolic conditions added about 1% of cases to the surveillance programs. Discussion: Enhancing birth defect surveillance programs can be an efficient strategy to develop and quickly deploy long-term follow-up of metabolic conditions, provided a systematic approach and best practices are followed. Background: Newborn screening using tandem mass spectrometry for some urea cycle disorders (UCD), like citrullinemia type I and argininosuccinate lyase deficiency (ASLD), was introduced in Austria in 2003. This brought new challenges for follow up and treatment in patients with mostly mild variants. Patients: 13 patients with persistent hypercitrullinemia (Cit >50 μmol/l) were detected. Initially measured mean citrulline for citrullinemia was 214 μmol/l; range 72-704; for ASLD 85 μmol/l; range 60-96. Results: ASLD was confirmed by enzyme activity measurement in erythrocytes in three children. One of these patients had already developed a severe hyperammonemic crisis prior to arrival of the screening result; the others were asymptomatic in the neonatal period. In the other children citrullinemia type I was confirmed by ASS gene mutation analysis. One patient was symptomatic with classical neonatal-onset citrullinemia type I prior to the screening result. Conclusion: Newborn screening for UCD may not prevent severe hyperammonemic crisis in early-onset forms as the results is available too late. Screening identifies many individuals with attenuated citrullinemia type I and ASLD of uncertain clinical relevance. Further studies of long-term outcome and phenotype/ genotype correlations are necessary to determine the value of newborn screening for these conditions. Background: With more than 350 different diseases identified to date, IEMs represent about one-third of genetic diseases, nevertheless they are overlooked as cause of neurologic disorders in adults. Methods: Our study involved 192 patients evaluated in the neurogenetics clinics by geneticists and neurologists in a two-year period. Clinical anamnesis, physical exam, neuroimaging studies , ophtalmological and auditory evaluations, neurophysiological studies, biochemical tests, muscle biopsy with respiratory chain mitochondrial enzymes, lysosomal and peroxisomal studies and, when indicated, nerve/skin biopsy for EM studies and karyotype were performed in the course of the investigation. Results: IEMs were identified in 62 patients. Adrenomyeloneuropathy, AVED, abetalipoproteinemia, Fabry disease, Niemann-Pick type C, OTC deficiency, intermitent acute porphyria and mitochondrial disorders were the commonest IEMs diagnosed. Lesch-Nyhan syndrome, AMACR deficiency, cerebrotendineous xanthomatosis and coenzyme Q10 deficiency were other rare IEMs identified. In 93 patients, it was possible to rule out an IEM as cause of the neurological syndrome; 37 patients are still under investigation. Conclusion: Hereditary metabolic disorders can be an important cause of neurological disorders in adults and should not be missed, specially because many IEMs are often treatable diseases and, even the absence of a specific treatment, genetic counselling can be offered to the families. Objectives: The aim of our study was to evaluate IMD patients' satisfaction with the transition process and detect how it could be ameliorated. Methods: A group of 93 adult patients with amino acids, carbohydrate, urea cycle defects, organic acidurias and lysosomal disorders were included. The adult outpatient clinic is located at the Division of Neurology of the St. Bassiano Hospital. The transition process considered the last visit in the pediatric setting and the first two visits in the adult one. Perceived satisfaction was evaluated with a questionnaire-interview through three main domains: patients'care, psychological aspects, logistics. Results: The majority of patients were satisfied (90%). Positive features reported were: perception of independence and greater sense of control; the presence of new adult specialists required for adult care (i.e. vulnologist, cardiologist, gynecologist); regular clinical contacts with the adult metabolic expert, adult specialists and metabolic pediatricians; the neuropsychologist serves as the transition process reference. Major complaints were: lack of dietitian in the adult center; distance between the centers (50 km). Conclusions: The transition process for IMD patients is a fundamental process that cannot be deferred. The major achievement for the patients is an improved self-consciousness of their disease and increase personal management of therapy. Clinical guidelines suggest that adolescents should be seen on their own for part of clinic consultation. However, little is known of parental attitudes on this issue. We explored the views of parents of adolescents in our Metabolic Clinic, in which this is standard practice. Of 40 eligible parents, 33 completed a questionnaire handed to them in clinic, seeking parental understanding of confidentiality, their views about when information should be shared with them, and their perception of benefits/concerns of consulting with young people alone. The main advantages parents identified in adolescents seeing clinicians alone were: practicing talking to the doctor alone; taking responsibility for their own health; help them become more mature. Concerns identified included the possibility of not being informed about important issues (including eating disorders, cigarette smoking, alcohol and illicit drug use, pregnancy, and problems with parents); not being informed of the treatment plan, and concerns about their child possibly not understanding the issues or not remembering the treatment plan. Parental understanding of a confidential consultation with young people alone was remarkably similar to that in a general adolescent clinic (N=86). Background: Ornithine transcarbamylase (OTC) deficiency is an inherited metabolic disorder, better known to pediatrician because it is usually diagnosed during the neonatal period. Descriptions of late-onset forms are scarce but they are often fatal due to hyperammonemia. We report five adults who presented with various OTC deficiency symptoms after the age of 25 years. Patients and Methods: We retrospectively studied five patients (three males, two females), and collected clinical, biochemical and molecular features. Results: A 65-year old man, a 57-year old and a 43-year old female presented with acute neurological symptoms after unusually high protein intake. Ammonemia was high (78 to 327 μmol/L), associated with high orotic aciduria excretion. They were successfully treated with protein restriction and high caloric diet, a supply of ammonia scavenging medication, and hemodialysis in two cases. Two other asymptomatic brothers were diagnosed at 36 and 26 years of age after systematic screening owing to two fatal cases in their family. OTC deficiency was confirmed by DNA sequencing in four cases. Conclusion: OTC deficiency can present with a large spectrum of clinical characteristics. We report five cases of late-onset presentation of OCT deficiency, including the oldest one to our knowledge in the literature.