We have used retrospective analysis of 123 reported cases of HPRT deficiency, published between 1983 to 2003. They are not representative for the Bulgarian popu­lation. We considered them relevant for the review, be­cause they represent a heterogeneous group of alterations throughout the HPRT gene that express all four pheno­types considered below. We have also accepted the classi­fication of the HPRT deficiency phenotypes that are the result of recent clinical, biochemical, enzymatic, and molecular genetic studies on 22 patients from 18 Spanish families. Based on the neurological symptoms, depend­ency for personal care, HPRT activity in hemolysates and in intact erythrocytes, and predicted protein size, patients were classified into four clinical types. We will call these four phenotypes, clinical variants 1, 2, 3 and 4, respec­tively.

Type 1: normal development with no neurological symptoms, HPRT activity is detectable in hemolysates and in intact erythrocytes, and the mutation does not affect the predicted protein size.

Type 2: mild neurological symptoms that do not pre­vent independent lives, HPRT activity is detectable in intact erythrocytes, and the protein size is normal.

Type 3: severe neurological impairment that preclude an independent life, no residual HPRT activity and nor­mal protein size.

Type 4: clinical characteristics of LNS (some do not show self-injurious behavior), no residual HPRT activity, and in most, the mutation affects the predicted protein size [2].