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
Reference:
- 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
- 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
- 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.