Abstract
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome (OMIM 238970) is an autosomal recessive disorder that is caused by a deficiency of mitochondrial ornithine transporter 1, resulting in dysfunction of the urea cycle. HHH is the rarest of the urea cycle disorders, reported in fewer than 100 patients. It is characterized by extreme phenotypic variability, including diverse ages of onset and severity of phenotype. We report the first confirmed instance of HHH syndrome in a premature infant (31 2/7 weeks) with severe hyperammonemia (1,300 μmol/L).
This case highlights the importance of considering HHH in the differential diagnosis for neonatal hyperammonemia. Because HHH is not detected by newborn screening, and the characteristic biochemical triad may be subtle or even absent, it has the potential to be underdiagnosed; however, making the diagnosis has critical therapeutic implications as treatment is distinct from other urea cycle defects. For instance, lysine supplementation is a beneficial treatment unique to HHH. Therefore, we present here a review of previously reported cases in order to demonstrate the full spectrum of the disease and highlight potentially diagnostic features.
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Abbreviations
- ASA:
-
Argininosuccinate
- CPS I:
-
Carbamoyl phosphate synthetase I
- CSF:
-
Cerebrospinal fluid
- DOL:
-
Day of life
- HHH:
-
Hyperornithinemia-hyperammonemia-homocitrullinuria
- INR:
-
International normalized ratio
- LP:
-
Lumbar puncture
- OTC:
-
Ornithine transcarbamylase
- TPN:
-
Total parenteral nutrition
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The authors thank the family for their participation in this work.
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Communicated by: Bridget Wilcken, MBChB, MD
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RDG received salary support from the National Institute of Diabetes and Digestive and Kidney diseases, K08-DK113250.
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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
Hyperornithinemia-hyperammonemia-homocitrullinuria is an important consideration in the evaluation of a neonate with hyperammonemia, even if the characteristic biochemical triad is not yet apparent.
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The authors each declare that they have no conflict of interest.
Details of the contributions of individual authors: KTW performed clinical and biochemical evaluation of the patient and conceived and wrote the manuscript. RDG performed clinical and biochemical evaluation of the patient, conceived the manuscript, and provided oversight. MY performed clinical and biochemical evaluation of the patient and edited and conceived the manuscript. LIC performed clinical evaluation of the patient and edited and conceived the manuscript.
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© 2018 Society for the Study of Inborn Errors of Metabolism (SSIEM)
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Wild, K.T., Ganetzky, R.D., Yudkoff, M., Ierardi-Curto, L. (2018). Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Syndrome Causing Severe Neonatal Hyperammonemia. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 44. JIMD Reports, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2018_132
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DOI: https://doi.org/10.1007/8904_2018_132
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