Skip to main content

Tyrosinemia, Type II

OMIM ID:

autosomal recessive

Tyrosinemia, Type II

Alternate Names

oculocutaneous tyrosinosis
Richner-Hanhart syndrome
TAT deficiency
keratosis palmoplantaris with corneal dystrophy
Oregon type tyrosinemia
tyrosine aminotransferase deficiency

Defective Genes

TAT

Clinical Characteristics

Ocular Features

Keratitis is the outstanding ocular manifestation but not all patients have corneal involvement.  Symptoms include photophobia, pain, tearing, and redness which may occur as early as one year of age.  Corneal neovascularization, ulceration and scarring may lead to decreased visual acuity.  Linear and star-like corneal opacities in the epithelium resembling dendrites (pseudodendritic keratitis) have been described together with thickening of the conjunctiva.  The corneal lesions do not stain.  The conjunctival epithelium, fibrocytes, and blood vessel endothelial cells contain an accumulation of large inclusion bodies and tyrosine crystal-like structures. 

Systemic Features

Hydroxyphenylpyruvic acid is elevated in the urine and serum tyrosine levels are increased as the result of a defect in tyrosine aminotransferase.  Some patients have severe mental and somatic retardation.  The palms and soles can have painful punctate keratosis which may extend to the digits.  Developmental milestones such as walking are often delayed.  The keratotic lesions may be up to 2 cm in size. 

Genetics

Inheritance

Tyrosinemia type II is an autosomal recessive disorder caused by mutations in the tyrosine aminotransferase (TAT) gene at 16q22.1-q22.3. 

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

The hyperkeratosis and corneal opacities may improve with a diet low in phenylalanine and tyrosine but can recur after liberalization of the diet.  Benefits, if any, on CNS symptoms are unknown. 

Selected Resources

Publications

Displaying 1 - 4 of 4

Painful keratoderma and photophobia: Hallmarks of tyrosinemia type II

PubMedID: 7844676

Richner-Hanhart syndrome (tyrosinaemia-II) (report of four cases without ocular involvement)

PubMedID: 6453606

The Richner-Hanhart Syndrome: Report of a Case With Associated Tyrosinemia

PubMedID: 180943

Tyrosinemia type II: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation

PubMedID: 28255985