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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2024

Open Access 01-12-2024 | Ornithine Transcarbamylase Deficiency | Research

Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease

Authors: Barbara Siri, Giorgia Olivieri, Francesca Romana Lepri, Martin Poms, Bianca Maria Goffredo, Anna Commone, Antonio Novelli, Johannes Häberle, Carlo Dionisi-Vici

Published in: Orphanet Journal of Rare Diseases | Issue 1/2024

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Abstract

Background

Ornithine Transcarbamylase Deficiency (OTCD) is an X-linked urea cycle disorder characterized by acute hyperammonemic episodes. Hemizygous males are usually affected by a severe/fatal neonatal-onset form or, less frequently, by a late-onset form with milder disease course, depending on the residual enzymatic activity. Hyperammonemia can occur any time during life and patients could remain non- or mis-diagnosed due to unspecific symptoms. In heterozygous females, clinical presentation varies based on the extent of X chromosome inactivation. Maternal transmission in X-linked disease is the rule, but in late-onset OTCD, due to the milder phenotype of affected males, paternal transmission to the females is possible. So far, father-to-daughter transmission of OTCD has been reported only in 4 Japanese families.

Results

We identified in 2 Caucasian families, paternal transmission of late-onset OTCD with severe/fatal outcome in affected males and 1 heterozygous female. Furthermore, we have reassessed the pedigrees of other published reports in 7 additional families with evidence of father-to-daughter inheritance of OTCD, identifying and listing the family members for which this transmission occurred.

Conclusions

Our study highlights how the diagnosis and pedigree analysis of late-onset OTCD may represent a real challenge for clinicians. Therefore, the occurrence of paternal transmission in OTCD should not be underestimated, due to the relevant implications for disease inheritance and risk of recurrence.
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Metadata
Title
Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease
Authors
Barbara Siri
Giorgia Olivieri
Francesca Romana Lepri
Martin Poms
Bianca Maria Goffredo
Anna Commone
Antonio Novelli
Johannes Häberle
Carlo Dionisi-Vici
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2024
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-023-02997-8

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