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New UCD research: Researchers document father-to-daughter transmission in late-onset OTC deficiency

A research team exploring the inheritance patterns of late-onset ornithine transcarbamylase deficiency (OTC deficiency) has described two Caucasian families showing paternal transmission of the disorder in the Orphanet Journal of Rare Diseases. Previously, father-to-daughter OTC deficiency transmission had only been documented in four Japanese families. 

OTC deficiency, the most common urea cycle disorder, is an x-linked recessive trait that allows ammonia to build up in the blood. It is most often assumed to be passed from the mother to their affected children (maternal inheritance).

In one family studied by the researchers, two brothers with mild OTC deficiency had three daughters with symptoms ranging from a severe, fatal hyperammonemic episode at age 43 in one female to milder symptoms in the other two females. In the second family, molecular analysis identified four father-to-daughter, three mother-to-daughter and one mother-to-son transmissions, with presentations ranging from fatal to asymptomatic.

The study team was led by Carlo Dionisi-Vici of Bambino Gesù Children’s Hospital in Rome, Italy. Study authors say that the diagnosing and tracing the inheritance of OTCD can be challenging for clinicians. However, they say, the occurrence of father-to daughter transmission in OTCD should not be underestimated, as it has significant implications for disease inheritance and risk of recurrence. Read more:

Citation: Siri B, Olivieri G, Lepri FR, Poms M, Goffredo BM, Commone A, Novelli A, Häberle J, Dionisi-Vici C. Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease. Orphanet J Rare Dis. 2024 Jan 2;19(1):3. doi: 10.1186/s13023-023-02997-8. PMID: 38167094; PMCID: PMC10763478.

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