title: Argininosuccinic Acid Lyase Deficiency Missed by Newborn Screen.
abstract: Argininosuccinic acid lyase (ASL) deficiency, caused by mutations in the ASL gene (OMIM: 608310) is a urea cycle disorder that has pleiotropic presentations. On the mild end, ASL deficiency can manifest as nonspecific neurocognitive abnormalities without readily identifiable signs to differentiate it from other causes of intellectual disability or learning disabilities. Dietary management and arginine supplementation, if initiated early, may ameliorate symptoms.Because of the nonspecific nature of the symptoms and the possibility for therapeutic management, ASL deficiency is part of the recommended uniform screening panel for newborn screening in the USA. We report here a case of ASL deficiency that was missed on newborn screening in the USA.The case reported here has two known pathogenic mutations - one with no residual activity and one with reported 10% residual activity. Review of this newborn screening results showed subtle elevation of citrulline, overlapping the normal range. These findings suggest that newborn screening may be missing other patients with ASL deficiency with at least one hypomorphic allele. This case was diagnosed incidentally, but in retrospect had symptoms best attributed in full or in part to his ASA deficiency, including protein aversion, developmental delay, and seizures. This case highlights the importance of considering ASL deficiency in patients with nonspecific abnormal neurocognitive signs, such as epilepsy and developmental delay, even when newborn screening was normal.
authors: Department of Pediatrics, Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Philadelphia, PA, 19104, USA.
authors: Rebecca D
authors: RD
authors: Ganetzky
authors: Department of Pediatrics, Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Philadelphia, PA, 19104, USA.
authors: Emma
authors: E
authors: Bedoukian
authors: Department of Pediatrics, Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Philadelphia, PA, 19104, USA.|Department of Pediatrics, Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Philadelphia, PA, 19104, USA.
authors: Matthew A
authors: MA
authors: Deardorff
authors: Department of Pediatrics, Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Philadelphia, PA, 19104, USA. ficicioglu@email.chop.edu.
authors: Can
authors: C
authors: Ficicioglu
keywords: Argininosuccinic aciduria; Intellectual disability; Neonatal screening; Urea cycle disorders