Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease.
Orphanet J Rare Dis
; 19(1): 3, 2024 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-38167094
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença da Deficiência de Ornitina Carbomoiltransferase
/
Hiperamonemia
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
Orphanet J Rare Dis
Ano de publicação:
2024
Tipo de documento:
Article