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Survival of a Male Infant with a Familial Xp11.4 Deletion Causing Ornithine Transcarbamylase Deficiency

  • Molly McPheronEmail author
  • Melissa Lah
Research Report
Part of the JIMD Reports book series (JIMD, volume 45)

Abstract

Ornithine transcarbamylase (OTC) deficiency is well known to cause severe neonatal hyperammonemia in males with absent enzyme activity. In families with large deletions of the X chromosome involving OTC and other contiguous genes, male infants appear to have an even more severe course. Notably, there are no published reports of these males surviving to liver transplant, even in cases where the diagnosis was known or suspected at birth. We describe two male newborns and their mother who all have a 1.5-Mb deletion of Xp11.4 encompassing the genes TSPAN7, OTC, and part of RPGR. The first child succumbed to his illness on his fourth day of life. His younger brother was diagnosed prenatally, and with early aggressive treatment, he survived the neonatal period. He suffered multiple life-threatening complications but stabilized and received a liver transplant at 7 months of age. This report demonstrates both the possibility of survival and the complications in caring for these patients.

Notes

Acknowledgments

We want to thank the patients’ family for agreeing to participate in this report and for their amazing care of these young boys. We also acknowledge Dr. Bryan Hainline, Dr. Alyce Belonis, genetic counselors Katie Sapp and Kristyne Stone, and the rest of our care team who contributed greatly to the patients’ clinical care.

References

  1. Arranz JA, Madrigal I, Ruidor E, Armengol L, Mila M (2007) Complete deletion of ornithine transcarbamylase gene confirmed by CGH array of X chromosome. J Inherit Metab Dis 30:813CrossRefGoogle Scholar
  2. Balasubramaniam S, Rudduck C, Bennetts B, Peters G, Wilcken B, Ellaway C (2010) Contiguous gene deletion syndrome in a female with ornithine transcarbamylase deficiency. Mol Genet Metab 99:34–41CrossRefGoogle Scholar
  3. Batshaw M, Tuchman M, Summar M, Seminara J (2014) A longitudinal study of urea cycle disorders. Mol Genet Metab 113:127–130CrossRefGoogle Scholar
  4. Caldovic L, Abdikarim I, Narain S, Tuchman M, Morizono H (2015) Genotype-phenotype correlations in ornithine transcarbamylase deficiency: a mutation update. J Genet Genomics 42(5):181–194CrossRefGoogle Scholar
  5. Deardoff MA, Gaddipati H, Kaplan P et al (2008) Complex management of a patient with a contiguous gene deletion involving ornithine transcarbamylase: a role for detailed molecular analysis in complex presentations of classical diseases. Mol Genet Metab 94:498–502CrossRefGoogle Scholar
  6. Gallant NM, Gui D, Lassman C et al (2015) Novel liver findings in ornithine transcarbamylase deficiency due to Xp11.4-p21.1 microdeletion. Gene 556:249–253CrossRefGoogle Scholar
  7. Jain-Ghai S, Skinner S, Hartley J, Fox S, Buhas D, Rockman-Greenberg C, Chan A (2015) Contiguous gene deletion of chromosome Xp in three families encompassing OTC, RPGR, and TSPAN 7 genes. J Rare Disord 1:1Google Scholar
  8. McCullough BA, Yudkoff M, Batshaw ML, Wilson JM, Raper SE, Tuchman M (2000) Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype. Am J Med Genet 93:313–319CrossRefGoogle Scholar
  9. Old JM, Purvis-Smith S, Wilcken B et al (1985) Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis. Lancet 325(8420):73–75CrossRefGoogle Scholar
  10. Ono M, Tsuda J, Mouri Y, Arai J, Arinami T, Noguchi E (2010) Contiguous Xp11.4 gene deletion leading to ornithine transcarbamylase deficiency detected by high-density single-nucleotide array. Clin Pediatr Endocrinol 19(2):25–30CrossRefGoogle Scholar
  11. Quental R, Azevedo L, Rubio V, Diogo L, Amoriam A (2009) Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene. Clin Genet 75:457–464CrossRefGoogle Scholar
  12. Segues B, Rozet JM, Gilbert B et al (1995) Apparent segregation of null alleles ascribed to deletions of the ornithine transcarbamylase gene in congenital hyperammonemia. Prenat Diagn 15:757–761CrossRefGoogle Scholar
  13. Shchelochkov OA, Li FY, Geraghty MT et al (2009) High-frequency deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH. Mol Genet Metab 96:97–105CrossRefGoogle Scholar
  14. Tuchman M, Tsai MY, Holzknecht RA, Brusilow SW (1989) Carbamyl phosphate synthetase and ornithine transcarbamylase activities in enzyme-deficiency human liver measured by radiochromatography and correlated with outcome. Pediatr Res 26(1):77–82CrossRefGoogle Scholar
  15. Tuchman M, Morizono H, Rajagopal BS, Plante RJ, Allewell NM (1998) The biochemical and molecular spectrum of ornithine transcarbamylase deficiency. J Inherit Metab Dis 21(Suppl 1):40–58CrossRefGoogle Scholar
  16. Wilnai Y, Blumenfeld YJ, Cusmano K et al (2018) Prenatal treatment of ornithine transcarbamylase deficiency. Mol Genet Metab 123(3):297–300CrossRefGoogle Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  1. 1.Indiana University School of MedicineIndianapolisUSA

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