Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease
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, depend...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02997-8 |
| _version_ | 1827388114376589312 |
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| author | Barbara Siri Giorgia Olivieri Francesca Romana Lepri Martin Poms Bianca Maria Goffredo Anna Commone Antonio Novelli Johannes Häberle Carlo Dionisi-Vici |
| author_facet | Barbara Siri Giorgia Olivieri Francesca Romana Lepri Martin Poms Bianca Maria Goffredo Anna Commone Antonio Novelli Johannes Häberle Carlo Dionisi-Vici |
| author_sort | Barbara Siri |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T16:12:59Z |
| format | Article |
| id | doaj.art-12abc63a342d43f697765156f5a5ac26 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-08T16:12:59Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-12abc63a342d43f697765156f5a5ac262024-01-07T12:46:51ZengBMCOrphanet Journal of Rare Diseases1750-11722024-01-011911810.1186/s13023-023-02997-8Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked diseaseBarbara Siri0Giorgia Olivieri1Francesca Romana Lepri2Martin Poms3Bianca Maria Goffredo4Anna Commone5Antonio Novelli6Johannes Häberle7Carlo Dionisi-Vici8Division of Metabolic Diseases and Hepatology, Bambino Gesù Children’s Hospital, IRCCSDivision of Metabolic Diseases and Hepatology, Bambino Gesù Children’s Hospital, IRCCSTranslational Cytogenomics Research Unit, Laboratory of Medical Genetics, Bambino Gesù Children’s Hospital, IRCCSDivision of Clinical Chemistry and Biochemistry and Children’s Research Center, University Children’s Hospital Zurich, University of ZurichDivision of Metabolism and Metabolic Diseases Research Unit, Bambino Gesù Children’s Hospital, IRCCSDivision of Metabolic Diseases and Hepatology, Bambino Gesù Children’s Hospital, IRCCSTranslational Cytogenomics Research Unit, Laboratory of Medical Genetics, Bambino Gesù Children’s Hospital, IRCCSDivision of Metabolism and Children’s Research Center, University Children’s Hospital Zurich, University of ZurichDivision of Metabolic Diseases and Hepatology, Bambino Gesù Children’s Hospital, IRCCSAbstract 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.https://doi.org/10.1186/s13023-023-02997-8Ornithine transcarbamylase deficiency (OTCD)X-LinkedFather-to-daughter transmissionHyperammonemia |
| spellingShingle | Barbara Siri Giorgia Olivieri Francesca Romana Lepri Martin Poms Bianca Maria Goffredo Anna Commone Antonio Novelli Johannes Häberle Carlo Dionisi-Vici Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease Orphanet Journal of Rare Diseases Ornithine transcarbamylase deficiency (OTCD) X-Linked Father-to-daughter transmission Hyperammonemia |
| title | Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease |
| title_full | Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease |
| title_fullStr | Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease |
| title_full_unstemmed | Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease |
| title_short | Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease |
| title_sort | father to daughter transmission in late onset otc deficiency an underestimated mechanism of inheritance of an x linked disease |
| topic | Ornithine transcarbamylase deficiency (OTCD) X-Linked Father-to-daughter transmission Hyperammonemia |
| url | https://doi.org/10.1186/s13023-023-02997-8 |
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