A clinical or biochemical abnormality in the presence of a family pedigree characteristic of a particular mode of inheritance is generally assumed to represent an inborn error of metabolism, even though the precise enzymatic defect and the responsible gene have not been identified. Ideally, however, recognition of a heritable metabolic disorder should be reinforced by genetic and enzymatic studies on the molecular level.
Studies of enzymatic defects and gene mutations have confirmed the suspected genetic basis of many diseases. On occasions these studies have provided surprises, disclosing genetic determinants when least expected or changing preconceived ideas on the nature of the expected heritable trait. One such surprise is the recently discovered alpha antitrypsin deficiency in some patients with pulmonary emphysema, a disease hitherto not viewed in the context of heritable metabolic disorders. Another surprising discovery is that of a genetically distinct subtype of gout characterized by an x-chromosomelinked deficiency of
Phosphoribosyltransferase Deficiency Gout. JAMA. 1969;210(2):339–340. doi:10.1001/jama.1969.03160280079022