Jake is a 14-year-old boy who was diagnosed with the primary antibody deficiency X-linked agammaglobulinaemia (XLA). XLA has a recessive inheritance pattern, which means that females with the condition are asymptomatic carriers and males who inherit it will have symptoms. He was diagnosed shortly after birth, following hospitalisation for severe pneumonia. His mum, Rachel, was identified as a carrier of the genetic condition. Jake’s uncle had the same condition and died unexpectedly and prematurely due to a severe infection. He was very close to his uncle and was understandably upset by his death. Rachel was also upset about the death of her brother but also significantly distressed by the realisation of the risk posed by XLA to her son. Jake has been treated with immunoglobulin replacement therapy (to be discussed later in the chapter) since he was a baby and has adapted well to his treatment regime. He leads a relatively normal life with few infections and is able to participate in sports with his friends, being a keen hockey player. Jake has a younger sister Amy (10). As the daughter of a carrier, she has a 50% chance of being a carrier of XLA herself; however she has not yet been tested to determine if this is the case. It is usual practice to wait for asymptomatic children to be old enough to give fully informed consent before such testing is carried out. Jake has a 100% chance of passing on carrier status if he has a daughter in the future but any sons that he may have will be unaffected.

Rachel has two siblings who each have two children – no one else in the family is symptomatic: should her nieces and nephews be tested? What difference would their gender make in the decision to test?

If Rachel’s sibling is male and asymptomatic it is unlikely that they have the faulty gene, so their children will not be affected. If the brother is symptomatic, his daughters should be tested if they wish to know if they are a carrier of the affected gene. If Rachel has a sister, she should be tested to see if she is a carrier. Daughters of this sister have the potential to be asymptomatic carriers and sons could have XLA (symptomatic).

How may Jake’s uncle’s premature death affect the family and their perception of the condition?

The perceived risk of harm from the disease can be heightened so counselling should be offered. When a person has been coping with a condition, as Jake has been, the death of a relative can cause instability in management of symptoms. Teenagers are particularly vulnerable to the effect of this, so should be monitored for signs of non-adherence or psychological effects that may affect management of immunodeficiency. Having come to terms with the guilt of passing the condition to her son, and learning to administer treatment to allow a relatively normal life so far, Rachel is likely to be strongly affected by the realisation that XLA is life threatening condition and will fear for her child’s life. It is not possible to predict how an individual patient or relative may feel, but they will nearly always require additional support when a relative dies from the same condition.

How would you decide the appropriate age at which to offer Amy testing?

This would be entirely due to the individual person. You should work closely with Amy and her family to establish her level of comprehension and maturity to decide when to offer testing. All questions from Amy should be answered clearly and at an age/knowledge appropriate level.