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Case Reports
. 2024 Sep 28:41:101146.
doi: 10.1016/j.ymgmr.2024.101146. eCollection 2024 Dec.

OTC gene duplication as the possible cause of massive hyperammonaemia with a fatal prognosis

Borkowska Natalia  1 , Kaluzny Lukasz  2 , Rokicki Dariusz  3 , Szmida Elzbieta  4 , Kowalski Pawel  5 , Dus-Zuchowska Monika  2 , Skiba Pawel  4 , Ciara Elzbieta  6 , Biela Mateusz  7 , Rydzanicz Malgorzata  8 , Ploski Rafal  8 , Smigiel Robert  7
Affiliations
Case Reports

OTC gene duplication as the possible cause of massive hyperammonaemia with a fatal prognosis

Borkowska Natalia et al. Mol Genet Metab Rep. .

Abstract

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It may occur due to various changes to the OTC gene located on the X chromosome. Many sequence variants in the OTC gene result in different severity and require different types of molecular testing. We present a familial case of hyperammonemia possibly caused by the small CNV (duplication) within exon 2 of the OTC gene that was not detected by standard sequencing methods. In this case, the knowledge of the underlying molecular changes to the gene results in an appropriate approach to future sibling screening. Collecting more data, especially regarding rare variants of genetic disorders, is essential as it will help to create the best diagnostic-therapeutic path in prenatal and neonatal care in the future. Early diagnosis and treatment can lead to a better prognosis, and this case emphasizes the importance of understanding genetic changes in OTC deficiency.

Keywords: Duplication; Hyperammonaemia; OTC deficiency; OTC gene.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a MRI on day 8 of life - picture of diffuse cytotoxic edema, no signs of bleeding. b MRI at five weeks of age generalized atrophic changes in both brain hemispheres. Broad cisterns of the basal of the brain. T1 -T1-weighted image shows abnormal high signal intensity in frontal and parietal lobes, central furrows, subcortical islands, and basal ganglia. The white matter of both brain hemispheres has decreased volume and abnormal signal intensity, hyperintense on T2-weighted images, and hypointense on T1-weighted images, with cavities forming.
Fig. 2
Fig. 2
aCGH result arr[GRCh37] Xp11.4(38222727_38228269)x2 and affected gene.
Fig. 3
Fig. 3
a MLPA P079-A3 OTC proband result. b MLPA P079-A3 OTC mother's result.
See this image and copyright information in PMC

References

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