Challenges in diagnosing hawkinsinuria in adulthood: 2 cases from a single family

Hawkinsinuria, caused by an autosomal dominant gain-of-function variant of 4-hydroxyphenylpyruvate dioxygenase resulting in accumulation of 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin) and tyrosine, typically presents in the neonatal period. Here we report the case of a female adult patient in her early 20s presenting with childhood developmental delay and dyspraxia. She was initially referred to neurology, where baseline imaging and biochemistry were unremarkable. She was subsequently investigated for metabolic disorders, and it was found that plasma organic acids and amino acids were indicative of hawkinsinuria. Furthermore, her mother, who was asymptomatic, was also diagnosed with hawkinsinuria following family screening. Management was conservative, with regular monitoring of tyrosine and phenylalanine levels. Dietary restriction may be considered if tyrosine is elevated or patients become symptomatic. To our knowledge, this is the first reported case of hawkinsinuria presenting symptomatically in an adult patient and the second case of an asymptomatic adult being diagnosed from genetic testing.