Inherited purine enzyme deficiencies: prenatal diagnosis and heterozygote detection

A number of genetically determined enzyme defects leading to disturbances of purine metabolism can prenatally be monitored, and heterozygote detection is possible in several cases. In severe hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency, associated with a neurological disease known as the Lesch-Nyhan Syndrome, rapid prenatal diagnosis can be performed by means of a simple quantitative radiochemical enzyme assay at the single cell level. In this X-linked recessive disease, the female heterozygotes can be detected by using cultured skin fibroblasts, but alternatively single hair root enzymes can directly be assayed. Two other genetic purine enzyme defects lead to deranged immune function: in adenosine deaminase (ADA) deficiency both T- and B-lymphocyte function are severely impaired. In purine nucleoside phosphorylase (PNP) deficiency, only certain T-cell abnormalities have been observed, with apparently normal B-cell function. Both diseases are transmitted as autosomal recessive traits. Prenatal diagnosis is possible, e.g. by means of the above mentioned microtechniques. Heterozygote detection can be done using blood cells or cultured fibroblasts. Microchemical methods offer the possibility to perform enzyme characterisation even when a very limited amount of material is available. In the case of HGPRT, ADA, and PNP, for a substrate affinity curve and pH optimum curve a few hundred cells are sufficient. These and other possibilities illustrate the general usefulness of simple microtechniques in clinical enzymology.