ESPE Abstracts

Background: Turner syndrome, a condition that affects only girls and women, result when the X chromosome is missing or partially missing. Ornithine transcarbamylase (OTC) deficiency, the most common inherited urea cycle disorder, is transmitted as a partially dominant X-linked trait. The OTC gene maps to Xp21.1 and spans approximately 73 kb, containing 10 exons and 9 introns. OTC deficiency is diagnosed using a combination of clinical findings and biochemical testing, while confirmation is often done using molecular genetics techniques. Here, we report two girls diagnosed with OTC deficiency and Partial Xp deletion.

Case 1: A 15-years-girl was diagnosed with OTC deficiency on the basis of clinical and biochemical findings including hyperammonemia, high level of glutamine and low citrulline in plasma and increased orotic acid in urine at 13 months of age. No mutation of OTC gene was identified by Sanger sequencing. Although ammonia was well-controlled with low protein diet and ammonia scavenging agents, the patient showed intellectual disability and autistic-like behavior. Subsequently, karyotyping was performed in the patient because she demonstrated profound short stature (height <3th percentile) and primary amenorrhea. High resolution chromosome study revealed a large deletion within chromosome X, bands p 21.1 to p 11.4.

Case 2: A 3 year-old girl was presented with lethargy and vomiting. At that time, plasma ammonia increased to 308 μmol/l (normal range <50 μmol/l) and the additional results of plasma amino acid analysis and urinary orotic acid were compatible with OTC deficiency. Targeted sequencing of OTC gene was normal, then multiplex ligand probe analysis revealed all nine exons deleted. As short stature and pigmented retinopathy were observed in the subject, the CGH microarray was performed additionally. We confirmed a deletion within chromosome X, bands p 21.1 to p 11.4, about 5 Mb.

Conclusion: We described two girls with rare inborn error disorder, OTC deficiency due to Xp deletion. Further evaluations will be needed to elucidate the role of X-linked genes in Turner syndrome.