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.
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Acknowledgements
The authors thank the family for their participation in this work, and Michael Bennett and Miao He who assisted with troubleshooting of clinical biochemical testing. We also thank Piero Rinaldo MD, PhD for reading of the manuscript and valuable suggestions.
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Communicated by: Bridget Wilcken
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RDG received salary support from the National Phenylketonuria Alliance through the Koch Memorial Fellowship.
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Ethics approval was not required for this study.
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None of the authors have any conflicts of interest to disclose.
Synopsis
Argininosuccinic acid lyase deficiency is an important consideration in a patient with nonsyndromic intellectual disability and can be missed by newborn screening.
Details of the Contributions of Individual Authors
RDG performed clinical and biochemical evaluation of the patient, conceived, and wrote the manuscript. EB and MAD performed clinical evaluation of the patient and were responsible for genetic testing. CF conceived the manuscript, provided oversight, and served as the guarantor for the article.
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Ganetzky, R.D., Bedoukian, E., Deardorff, M.A., Ficicioglu, C. (2016). Argininosuccinic Acid Lyase Deficiency Missed by Newborn Screen. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 34. JIMD Reports, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_2
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DOI: https://doi.org/10.1007/8904_2016_2
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