Tyrosinaemia

Tyrosinaemia can occur in a number of inborn errors of metabolism.

Tyrosinemia type I (hepatorenal tyrosinemia, HT-1)

• is an autosomal recessive condition (OMIM 276700)
• resulting in hepatic failure with comorbidities involving the renal and neurologic systems
• clinical symptoms
  • typically begin before 2 years of age, with the majority of children presenting before the age of 6 months with evidence of acute liver failure and renal dysfunction
  • neurologic crises, manifesting as painful episodes affecting extremity and/or abdominal function, accompanied by hypertension and hyponatremia, may present at any time and may result in respiratory failure and death
  • a few affected children may present over the age of 2 years with isolated coagulopathy or other signs of liver dysfunction, renal tubular disease, hypophosphatemic rickets, and failure to thrive
  • all children with HT-1 are at high risk for hepatocellular carcinoma (HCC)
  • an effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC, nitisinone) exists but requires early identification of affected children for optimal long-term results

Tyrosinemia type II (also known as oculocutaneous tyrosinemia and Richner-Hanhart syndrome)

• is a rare distinctive disorder with autosomal recessive inheritance, characterized by skin and eye lesions, and occasionally learning disability (2)
• approximately half of the hitherto reported cases are of Italian descent
• is distinct from the more severe hepatorenal tyrosinemia (tyrosinemia type I) and from benign transient tyrosinemia of the new-born
• caused by a deficiency of the hepatic enzyme tyrosine aminotransferase (TAT), which leads to increased levels of tyrosine in the blood and urine
• TAT gene is located on the long arm of chromosome 16, the exact locus being 16q22-24
• Tyrosinemia type II with features confined to the skin has been reported previously
  • typical dermatologic findings are painful, well-demarcated hyperkeratosis on the palms and soles, although the palms can be unaffected
  • on the palms the distribution usually involves the fingertips, and the thenar and hypothenar eminences, while the lesions on the soles are on the weight-bearing areas
  • lesions may begin as bullae and erosions that progress to crusted, hyperkeratotic plaques, are often associated with hyperhydrosis
  • age at onset of skin lesions can range from the first week of life to the second decade.
• ocular manifestations
  • can develop as early as the first day of life and alternatively may present for the first time as late as the fourth decade
  • early signs are photophobia, pain, tearing and redness, while late signs include corneal clouding and central or paracentral opacities, superficial or deep dendritic ulceration, corneal neovascularization, and corneal scars

In the UK, the he NHS has added HT-1 to the NHS Newborn Blood Spot Screening Programme in England, following a recommendation by the UK National Screening Committee (4):

• this condition will now be screened for, in the blood test that babies get on the fifth day after they are born, taken from the heel

Reference:

1. Chinsky JM, Singh R, Ficicioglu C, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017;19(12):. doi:10.1038/gim.2017.101
2. Al-Ratrout JT, Al-Muzian M, Al-Nazer M, Ansari NA. Plantar keratoderma: a manifestation of tyrosinemia type II (Richner-Hanhart syndrome). Ann Saudi Med. 2005;25(5):422-424. doi:10.5144/0256-4947.2005.422
3. Locatelli F, Puzenat E, Arnoux JB, Blanc D, Aubin F. Richner-Hanhart syndrome (tyrosinemia type II). Cutis. 2017 Dec;100(6):E20-E22. PMID: 29360903.
4. NHS England (October 14th 2025). NHS to screen all newborn babies for life-threatening metabolic disorder