9. Case Study 8

A 1 week old girl presented with a woresning encephalopathy. Her blood ammonia was raised at 900 mol/l. A diagnosis of OTC was made and confirmed by finding a full deletion of the OTC gene on one of her X chromosomes. On family studies her mother and maternal grandmother were also found to have the same deletion. However both were in good health. The mother had a normal allopurinol load and tolerated a protein load without any increase in ammona. However the grandmother showed a persistent increase in urine of orotic acid. She had 2 brothers who had died in the neontal period

The following pedigree was ascertained:

Comment: At first glance, this case looks as if there are two diseases at play here. However, what this this family displays is the phenomenon referred as random X-inactivation. References 42, 43, and 44 should be read for more details in this phenomenon in X Linked conditions as well as discussion on the mutations in OTC.

You will note from reference ref 42 that conventional mutation anlaysis may fail to detect such deletions.

Learning objectives from this case report:

1. To understand that random X-inactication can lead to very different phenotypes in women, heterozygous for OTC deficiency eithin the same family
2. To undertsand the value of mutation analysis as a means of confirmation of diagnosis but aslo in some situations in males as an indicator of severity.