hawkinsinuria hawkinsinuria hawkinsinuria is an autosomal dominant metabolic disorder affecting the metabolism of tyrosine. hawkinsinuriaother names4-alpha-hydroxyphenylpyruvate hydroxylase deficiencyhawkinsinspecialtyendocrinology normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-hydroxyphenylpyruvate dioxygenase. complete deficiency of this enzyme would lead to tyrosinemia iii. in rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid, but is unable to convert this intermediate to homogentisate. the intermediate then spontaneously reacts with glutathione to form 2-l-cystein-s-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin). patients present with metabolic acidosis during the first year of life, and growth arrest around the time of weaning off breast milk. treatment involves a diet containing a low amount of phenylalanine and tyrosine. tolerance toward these amino acids normalizes as the patients get older. then only a chlorine-like smell of the urine indicates the presence of the condition. patients have a normal life and do not require treatment or a special diet. the production of hawkinsin is the result of a gain-of-function mutation. inheritance of hawkinsinuria is therefore autosomal dominant (presence of a single mutated copy of the gene causes the condition). the gene affected is the hpd gene encoding 4-hydroxyphenylpyruvic acid dioxygenase, on chromosome 12q24. it is unusual in that most other inborn errors of metabolism are caused by loss-of-function mutations, and hence have recessive inheritance (condition occurs only if both copies are mutated).