Case Letter

Richner-Hanhart Syndrome (Tyrosinemia Type II)

Cutis. 2017 December;100(6):E20-E22

References

Scott CR. The genetic tyrosinemias. Am J Med Genet C Semin Med Genet. 2006;142C:121-126.
Meissner T, Betz RC, Pasternack SM, et al. Richner-Hanhart syndrome detected by expanded newborn screening. Pediatr Dermatol. 2008;25:378-380.
Natt E, Kida K, Odievre M, et al. Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. Proc Natl Acad Sci USA. 1992;89:9297-9301.
Charfeddine C, Monastiri K, Mokni M, et al. Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations. Mol Genet Metab. 2006;88:184-191.
Legarda M, Wlodarczyk K, Lage S, et al. A large TAT deletion in a tyrosinaemia type II patient. Mol Genet Metab. 2011;104:407-409.
Culic V, Betz RC, Refke M, et al. Tyrosinemia type II (Richner-Hanhart syndrome): a new mutation in the TAT gene. Eur J Med Genet. 2011;54:205-208.
Pasternack SM, Betz RC, Brandrup F, et al. Identification of two new mutations in the TAT gene in a Danish family with tyrosinaemia type II. Br J Dermatol. 2009;160:704-706.
Macsai MS, Schwartz TL, Hinkle D, et al. Tyrosinemia type II: nine cases of ocular signs and symptoms. Am J Ophthalmol. 2001;132:522-527.
Kymionis GD, Kankariya VP, Kontadakis GA, et al. Isolated corneal pseudodendrites as the initial manifestation of tyrosinemia type II in monozygotic twins. J Pediatr Ophthalmol Strabismus.2012;49:E33-E36.
Iskeleli G, Bilgeç MD, Arici C, et al. Richner-Hanhart syndrome (tyrosinemia type II): a case report of delayed diagnosis with pseudodendritic corneal lesion. Turk J Pediatr. 2011;53:692-694.
Rehák A, Selim MM, Yadav G. Richner-Hanhart syndrome (tyrosinaemia-II)(report of four cases without ocular involvement). Br J Dermatol. 1981;104:469-475.
Viglizzo GM, Occella C, Bleidl D, et al. Richner-Hanhart syndrome (tyrosinemia II): early diagnosis of an incomplete presentation with unusual findings. Pediatr Dermatol. 2006;23:259-261.
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Tyrosinemia type II typically demonstrates ocular symptoms (75% of cases) that usually occur in the first year of life. ⁸ They are characterized by photophobia, redness, and increase of lacrimation. Examination reveals a superficial and bilateral punctate keratosis with corneal dystrophy, often misdiagnosed as herpetic keratosis, as in our case, which may delay the diagnosis. ^9,10 Bilateral ocular lesions are suggestive, even if they are asymmetric. ^8,11 Furthermore, negative fluorescein staining, negative culture, and resistance to antiviral treatment exclude the diagnosis of herpetic keratosis. ^9,10

Skin lesions (85% of cases) typically appear in the first year of life. They are characterized by painful, irregular, limited, punctate hyperkeratosis on the palms and soles. ¹ They are more frequent in weight-bearing areas and tend to improve during summer, possibly due to a seasonal change in dietary behavior. ^4,12 Hyperkeratotic papules in a linear pattern also have been described on the flexor aspects of the fingers or toes. ¹³ In our case, the lesions were misdiagnosed as warts for 6 months.

Retarded development affects 60% of patients with tyrosinemia type II. Expression of neurological symptoms is variable and could include mental retardation, nystagmus, tremors, ataxia, and convulsion. ⁴ Lifetime follow-up of these patients is recommended.

Early initiation of a tyrosine-phenylalanine-restricted diet in infancy is the most effective therapy for Richner-Hanhart syndrome. ¹³ The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into amino acid tyrosine. Thus, dietary treatment of Richner-Hanhart syndrome requires restricting or eliminating foods high in phenylalanine and tyrosine with protein "medical food" substitute. The dietary treatment allows resolution of both eye and skin symptoms after a few days or weeks and also may prevent mental retardation. It is effective in lowering the plasma level to less than 400 µmol/L. The diet must be introduced as soon as Richner-Hanhart syndrome is suspected. Supplementation with essential amino acids, vitamins, and trace elements is needed. Early screening of siblings in families with Richner-Hanhart syndrome history is recommended, even in the absence of clinical findings. Careful dietary control of maternal plasma tyrosine level must be considered during future pregnancy for women. ^4,14,15

Richner-Hanhart syndrome should be suspected in patients demonstrating cutaneous lesions, especially palmoplantar keratosis associated with bilateral pseudodendritic corneal lesions unresponsive to antiviral therapy.

Richner-Hanhart Syndrome (Tyrosinemia Type II)

References

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