Also known as tyrosinaemia type II (Richner-Hanhart syndrome)
TAT-pEDD is a rare genetic skin condition that causes erosive keratoderma on the soles and, unusually, follows the finger dermatoglyphics (epidermal ridges that constitute fingerprints) with light-sensitivity associated with ulcerations of the cornea1. Patients may also have neurological manifestations, most commonly intellectual disability. The condition is caused by a deficiency in a liver enzyme called tyrosine aminotransferase, which can cause an accumulation of tyrosine and its metabolites. Unlike tyrosinemia type I, there is no associated liver dysfunction. Thus, dermatologists should be aware of this background when treating children from countries where screenings are not performed as early diagnosis can prevent ocular and intellectual disability.
Biology
The TAT gene encodes tyrosine aminotransferase, the first enzyme involved in breakdown of amino acid tyrosine2. Without functional TAT, tyrosine cannot be properly metabolized and instead builds up in blood and tissues. Because tyrosine is poorly soluble, the accumulation of it eventually causes the precipitation of needle-like tyrosine crystals inside cells. These crystal structures can trigger inflammatory responses, leading to further cell damage and unregulated epidermal differentiation. This results in the painful plantar keratoderma patients with TAT-pEDD experience. Tyrosine crystals can further deposit on the surface of the eye, or the cornea, contributing to characteristic photophobia (light sensitivity) and changes in vision. If left untreated, patients may be susceptible to variable intellectual and developmental disabilities over time.
Prevalence
TAT-pEDD is a very rare skin condition with an incidence of less than one in 250,0003. Fewer than 100 individuals from various ethnic backgrounds have been reported, though the actual proportion of affected individuals is likely higher due to underdiagnosis4.
Recurrence Risk
TAT variants are autosomal recessive (AR), meaning two altered copies, one inherited from each parent, are needed to cause the condition5 (Figure 1).
Figure 1. Autosomal dominant (A) and autosomal recessive (B) inheritance patterns. Adapted from Woodis et al. 20246. (A) There is a 50% chance of recurrence. (B) There is a 25% chance of recurrence and a 50% chance of a child being a carrier of the pathogenic variant.
Treatments
Early diagnosis and proper dietary management can prevent or reduce the severity of visual and intellectual disability7. Lifelong restriction of dietary phenylalanine and tyrosine and low-protein diet supplemented with appropriate amino acid (phenylalanine-free and tyrosine-free), vitamin, and mineral supplements are an effective targeted treatment. Ongoing management includes regular monitoring of plasma tyrosine levels to guide dietary adjustments. Though diagnosis and treatment should always be guided by a physician experienced with the condition.
In conversation with a multispecialty health team, including ophthalmology, dermatology, and neurology, supportive care for patient-specific symptoms can be valuable in long-term treatment for TAT-pEDD. Lubricating eye drops and in more severe cases corneal surgery may be recommended for ocular manifestations. Some retinoid creams may be beneficial for epidermal keratoderma, and regular appointments with neurologist can be beneficial for tracking developmental milestones with age-appropriate testing.
Support Group
Connecting with other patients and families who experience similar features can be an important source of support, even if they don’t share the same affected gene. Through the PC Project community, patients and loved ones can learn from and support one another as they navigate a challenging skin condition together. Newsletters, virtual and in-person patient support meetings, and a private Facebook group offer individuals and families an understanding and compassionate community.
References
1. Sprecher E, Ishida-Yamamoto A, Schwartz J, et al. Palmoplantar epidermal differentiation disorders: a new classification toward pathogenesis-based therapy. British Journal of Dermatology. 2025;193(3):364-380. doi:10.1093/bjd/ljaf054
2. Goldsmith LA. Tyrosinemia II: lessons in molecular pathophysiology. Pediatr Dermatol. 1983;1(1):25-34. doi:10.1111/j.1525-1470.1983.tb01088.x
3. Bouyacoub Y, Zribi H, Azzouz H, et al. Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome. Gene. 2013;529(1):45-49. doi:10.1016/j.gene.2013.07.066
4. Janakiraman L, Sathiyasekaran M, Deenadayalan M, Ganesh R, Mahesh U. Richner Hanhart syndrome. Indian J Pediatr. 2006;73(2):161-162. doi:10.1007/BF02820213
5. Natt E, Kida K, Odievre M, Di Rocco M, Scherer G. Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. Proc Natl Acad Sci USA. 1992;89(19):9297-9301. doi:10.1073/pnas.89.19.9297
6. Woodis KM, Garlisi Torales LD, Wolf A, Britt A, Sheppard SE. Updates in Genetic Testing for Head and Neck Vascular Anomalies. Oral and Maxillofacial Surgery Clinics of North America. 2024;36(1):1-17. doi:10.1016/j.coms.2023.09.001
7. Peña‐Quintana L, Scherer G, Curbelo‐Estévez ML, et al. Tyrosinemia type II : Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation. Clinical Genetics. 2017;92(3):306-317. doi:10.1111/cge.13003
