crystalline retinopathy

Hyperoxaluria, Primary, Type I

Clinical Characteristics
Ocular Features: 

About 30% of patients with type I develop retinopathy and about half of those have a diffuse optic atrophy.  Oxalate crystal deposition can cause a 'fleck retina' picture sometimes described as a crystalline retinopathy.  There is wide variation in the retinal phenotype.  Retinal toxicity leads to early and progressive vision loss.  The RPE may respond with hyperpigmentation in the form of 'ringlets' in the posterior pole.  Retinal fibrosis has been described.  Some patients develop choroidal neovascularization.

Evaluation using EDI-OCT shows progressive deposition of oxalate crystals throughout the retina, pigment epiithelium, and choroid.

Systemic Features: 

The onset of this disease can occur any time from infancy to 25 years of age.  Failure to thrive can be a presenting sign in infants.  Most patients have glycolic aciduria and hyperoxaluria as the result of failure to transaminate glyoxylate to form glycine.  The result is deposition of insoluble oxalate crystals in various body tissues with nephrolithiasis and nephrocalcinosis often early signs.  Neurologic, cardiac, vascular, and kidney disease is often the result although oxalate crystals can be found throughout the body.  Arteriole occlusive disease may lead to gangrene, Raynaud phenomena, acrocyanosis and intermittent claudication.  Renal failure is common. 

Genetics

Hyperoxaluria type I is an autosomal recessive disorder resulting from a mutation in the alanine-glyoxylate aminotransferase gene (AGXT) located at 2q36-q37.  Failure of this liver peroxisomal enzyme to transaminate glyoxylate results in oxidation of this molecule to form oxalate.

Hyperoxaluria type II (260000) is caused by mutations in the GRHPR gene (9cen) and type III (613616) by mutations in DHDPSL (HOGA1) (10q24.2).  Urolithiasis is the only clinical feature in these types. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Some patients benefit from oral pyridoxine (B6) treatment in type I hyperoxaluria.  Renal transplantation by itself is only temporarily helpful since the enzymatic defect remains and the donor tissue becomes damaged as well.  Combined renal-liver transplantation should be considered instead because it corrects the primary metabolic error and can even reverse the accumulation of oxalate crystals. 

References
Article Title: 

Primary hyperoxaluria in infants

Jellouli M, Ferjani M, Abidi K, Zarrouk C, Naija O, Abdelmoula J, Gargah T. Primary hyperoxaluria in infants. Saudi J Kidney Dis Transpl. 2016 May-Jun;27(3):526-32.

PubMed ID: 
27215245

Primary hyperoxaluria

Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013 Aug 15;369(7):649-58. Review.

PubMed ID: 
23944302

Bietti Crystalline Corneoretinal Dystrophy

Clinical Characteristics
Ocular Features: 

The retina contains refractile glistening intraretinal crystals at all levels and choroidal vessels are said to be sclerosed.  The RPE atrophies and often forms pigment clumps.  The yellow-white crystals may be seen in the peripheral cornea and in the limbus.  Symptoms of night blindness and early vision loss begin about the third decade.  Night blindness is progressive as is the narrowing of the visual fields but this is highly variable between patients.  The visual field may show paracentral scotomas at some stage.  Central acuity can be normal until late in the disease when it becomes markedly impaired. Legal blindness can occur by the 5th decade of life. 

The ERG may show lack of rod and cone responses late in the disease and color vision may be lost.  However, the ffERG and mfERGs show decreases in amplitude of scotopic and photopic responses in all patients, even younger ones.  The EOG becomes abnormal in late stages.  The degree of involvement may be asymmetrical.  Complex lipid inclusions can be seen histologically in choroidal, conjunctival and skin fibroblasts, as well as in keratocytes and lymphocytes.

Crystalline deposits have been detected mostly in the proximal portions of RPE cells adjacent to degenerated retinal  areas.  Most common are circular hyperrefractive structures in the outer nuclear layer adjacent to areas of degeneration.  Some patients have cystoid macular edema. Others in late stages have fundus changes that resemble choroideremia.

Systemic Features: 

No other organ disease has been reported.

Genetics

This is an autosomal recessive disorder caused by mutations in the CYP4V2 gene (4q35.1) involved in fatty acid metabolism.

A homozygous CYP4V2 mutation has also been reported in patients with a choroideremia-like clinical phenotype.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment beyond low vision aids is available.

References
Article Title: 

Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2

Li A, Jiao X, Munier FL, Schorderet DF, Yao W, Iwata F, Hayakawa M, Kanai A, Shy Chen M, Alan Lewis R, Heckenlively J, Weleber RG, Traboulsi EI, Zhang Q, Xiao X, Kaiser-Kupfer M, Sergeev YV, Hejtmancik JF. Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet. 2004 May;74(5):817-26. Epub 2004 Mar 23.

PubMed ID: 
15042513
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