SG03 A rare diagnosis of tyrosinaemia type II in a patient with palmoplantar keratoderma

Abstract Tyrosinaemia type II is an autosomal recessive disorder characterized by elevated serum tyrosine. The condition results from pathogenic variants in the TAT gene leading to tyrosine aminotransferase deficiency, which disrupts normal tyrosine metabolism. The disorder typically manifests between age 2 and 4 years with ocular (corneal dystrophy), neurological (mild-to-moderate intellectual disability) and dermatological (palmoplantar keratoderma) signs. Tyrosinaemia type II is exceedingly rare, with an estimated incidence of < 1 in 250 000 individuals and fewer than 150 cases reported in the literature to date. We report a case of tyrosinaemia type II diagnosed in early adulthood. An 18-year-old male college student was referred to our dermatology service with painful and malodorous calluses affecting both hands and feet since age 6 years. A focal keratoderma was present on the plantar surface of the feet, with calluses present on the fingertips following the dermatoglyphics. Nails were normal. The patient was born in Afghanistan to related parents and reported similar symptoms affecting one paternal male cousin. However, neither his parents nor siblings were affected. The patient was otherwise healthy with no significant past medical history. A palmoplantar keratoderma panel revealed a homozygous missense mutation c.1250G>A (p.R417Q) in exon 12 of the TAT gene, consistent with tyrosinaemia type II. Serum tyrosine levels were elevated (944 μmol L−1, normal range 26–154), confirming the diagnosis. Intriguingly, the patient denied ocular symptoms (e.g. epiphora or photophobia) and did not display overt signs of intellectual disability. The patient was advised to commence a modified diet and was referred for further specialist evaluation by metabolic medicine and ophthalmology. This case highlights tyrosinaemia type II as a rare but important differential for the presentation of palmoplantar keratoderma, even in the absence of ocular symptoms and intellectual disability. Awareness of the presenting signs and symptoms of this condition could help to accelerate the diagnosis and allow initiation of a tyrosine- and phenylalanine-restricted diet, which is the most effective method of managing the condition.