Homozygotes for PNP deficiency are unable to catabolise these nucleosides, or deoxynucleosides, which consequently accumulate in body fluids. The presence of some T- helper cell function is considered to explain the relatively normal B cell function. Kinases for the other three nucleosides accumulating in PNP deficiency do not exist in human cells. Neurological symptoms, as in HPRT deficiency, show a broad spectrum, the most severe presentations occurring in patients with complete deficiency and including head-lag and excessive irritability, noted as early as 3 months. Although actual B cell numbers may be low, as a percentage of total lymphocytes they are normal.
Immunoglobulin levels are normal or increased.
Infections are less frequent than in ADA deficiency but otitis media is common. Patients become increasingly susceptible to varicella, vaccinia or cytomegalovirus and the majority have died from such viral infections. Many have been immunised prior to diagnosis with live vaccines, or given non-irradiated blood transfusions without effect, indicating some residual T cell function. Histological changes in the thymus at autopsy have been considered consistent with involution rather than a congenital absence of the thymus. Inheritance and incidence This disorder has been described in at least 30 patients.