hyperkeratosis

Tyrosinemia, Type II

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

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
Treatment
Treatment Options: 

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. 

References
Article Title: 

Mutation update, eleven novel mutations and description of five independent subjects with a novel founder mutation

Pena-Quintana L, Scherer G, Curbelo-Estevez ML, Jimenez-Acosta F, Hartmann B, Roche F, Meavilla-Olivas S, Perez-Cerda C, Garcia Segarra N, Giguere Y, Huppke P, Mitchell GA, Monch E, Trump D, Vianey-Saban C, Trimble ER, Vitoria-Minana I, Reyes-Suarez D, Ramirez-Lorenzo T, Tugores A. TYROSINEMIA TYPE II: Mutation update, eleven novel mutations and description of five independent subjects with a novel founder mutation. Clin Genet. 2017 Mar 3. doi: 10.1111/cge.13003. [Epub ahead of print].

PubMed ID: 
28255985

Sjogren-Larsson Syndrome

Clinical Characteristics
Ocular Features: 

The retina often has glistening white intraretinal dots which may be concentrated in the macula.  They have been found in 1 to 2 year old infants.  The macula may have ‘punched out’ lesions.  A pigmentary retinopathy is present in about 50% of patients and fluorescein angiography reveals a mottled hyperfluorescence. The cornea often has grayish stromal opacities that become vascularized, most commonly in the lower half.  Most patients have punctate keratitis resulting in marked photophobia.  Visual acuities can range from about 20/40 to finger counting.  The retinal changes may be progressive but EOG and ERG studies do not reveal abnormalities of retinal function.  VEPs though are often abnormal.  Ichthyosis may involve the lids and periorbital areas.

Systemic Features: 

The skin changes are present at birth and consist of an ichthyosiform erythroderma.  Hyperkeratosis is also present at birth and full blown ichthyosis develops during infancy.  The skin changes are most marked about the neck, flexion creases, and lower abdomen.  Scales in these areas are often darker than the surrounding skin.  Mental retardation may be mild to severe and spastic diplegia or quadriplegia is common but there is little evidence of progression.  There does not seem to be any correlation of age with the severity of neurological disease.

Genetics

Mutations in the ALDH3A2 gene (17p11.2) are responsible for this autosomal recessive disorder resulting in a deficiency of fatty aldehyde dehydrogenase. This can lead to long-chain fatty alcohol accumulation as demonstrated in the brain with proton magnetic resonance spectroscopy.

A form of Sjogren-Larsson syndrome with more severe neurologic signs is caused by recessive mutations in ELOVL4 (6p14,1),  Mutations in the same gene have been identified in patients with autosomal dominant Stargardt disease 3 (600110).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for this disorder but moisturizing skin treatments can be beneficial.

References
Article Title: 
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