Newborns main panel

Gene: OTC

Special Consideration: Females should be reported.

Additional Information: Report males and females. From BIMDG: Discussion with pathway reviewers about reporting heterozygous females given phenotypic diversity (neonatal onset to post-partum presentation to asymptomatic). Genotype cannot predict this as a lot of variability is due to variable skewing of X-inactivation in liver. Conclusion was to report female heterozygotes to facilitate treatment of those presenting early, and putting in place emergency regimen for others.

Created: 26 Sep 2024, 3:54 p.m. | Last Modified: 26 Sep 2024, 3:54 p.m.

Panel Version: 0.469

The mechanism of pathogenicity is loss-of-function (LOF).

Created: 1 Jun 2023, 2:39 p.m. | Last Modified: 1 Jun 2023, 2:39 p.m.

Panel Version: 0.137

https://search.clinicalgenome.org/kb/genes/HGNC:8512

Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.

Panel Version: 0.134

MOI reviewed by clinical team. Mafalda Gomes comment: Ornithine transcarbamylase (OTC) deficiency can occur as a severe neonatal-onset disease in males (but rarely in females) and as a post-neonatal-onset (also known as late-onset or partial deficiency) disease in males and females. Males and heterozygous females with post-neonatal-onset (partial) OTC deficiency can present from infancy to later childhood, adolescence, or adulthood.
David Comment: Hi Katrina and Mafalda
I think we should include OTC females in XLD given 15% risk during their lifetime (which is thought an under estimate) - https://www.ncbi.nlm.nih.gov/books/NBK154378/#otc-def.Clinical_Characteristics

Created: 10 Mar 2023, 10:37 a.m. | Last Modified: 27 Mar 2023, 9:57 a.m.

Panel Version: 0.45

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Ornithine transcarbamylase deficiency