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. 

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

References

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.

PubMedID: 27215245

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

PubMedID: 23944302

Derveaux T, Delbeke P, Walraedt S, Raes A, Van Laecke S, Leroy BP, De Zaeytijd J. DETAILED CLINICAL PHENOTYPING OF OXALATE MACULOPATHY IN PRIMARY HYPEROXALURIA TYPE 1 AND REVIEW OF THE LITERATURE. Retina. 2016  Nov;36(11) :2227-2235. Review. 

PubMedID: 27135212

Roth BM, Yuan A, Ehlers JP. Retinal and Choroidal Findings in Oxalate Retinopathy Using EDI-OCT. Ophthalmic Surg Lasers Imaging. 2012 Nov 1;43(6):S142-4.

PubMedID: 23357321

Beck BB, Hoyer-Kuhn H, Gobel H, Habbig S, Hoppe B. Hyperoxaluria and systemic oxalosis: an update on current therapy and future directions. Expert Opin Investig Drugs. Expert Opin Investig Drugs. 2013 Jan;22(1):117-29.

PubMedID: 23167815

Theodossiadis PG, Friberg TR, Panagiotidis DN, Gogas PS, Pantelia EM, Moschos MN. Choroidal neovascularization in primary hyperoxaluria. Am J Ophthalmol. 2002 Jul;134(1):134-7.

PubMedID: 12095827

Cochat P, Koch Nogueira PC, Mahmoud MA, Jamieson NV, Scheinman JI, Rolland MO. Primary hyperoxaluria in infants: medical, ethical, and economic issues. J Pediatr. 1999 Dec;135(6):746-50.

PubMedID: 10586179

Small KW, Letson R, Scheinman J. Ocular findings in primary hyperoxaluria. Arch Ophthalmol. 1990 Jan;108(1):89-93.

PubMedID: 2297338