Primary hyperoxaluria

Primary hyperoxaluria is a rare condition (autosomal recessive), resulting in increased excretion of oxalate (up to 600mg a day from normal 50mg a day), with oxalate stones being common.

Primary hyperoxaluria
SpecialtyObstetrics and gynaecology, urology, medical genetics, endocrinology 

Signs/symptoms

Pathophysiology

The buildup of oxalate in the body causes increased renal excretion of oxalate (hyperoxaluria), which in turn results in renal and bladder stones. Stones cause urinary obstruction (often with severe and acute pain), secondary infection of urine and eventually kidney damage.

Oxalate stones in primary hyperoxaluria tend to be severe, resulting in relatively early kidney damage (say teenage, early adulthood), which impairs the excretion of oxalate leading to a further acceleration in accumulation of oxalate in the body.

After the development of renal failure patients may get deposits of oxalate in the bones, joints and bone marrow. Severe cases may develop haematological problems such as anaemia and thrombocytopaenia. The deposition of oxalate in the body is sometimes called "oxalosis" to be distinguished from "oxaluria" which refers to oxalate in the urine.

Renal failure is a serious complication requiring treatment in its own right. Dialysis can control renal failure but tends to be inadequate to dispose of excess oxalate. Renal transplant is more effective and this is the primary treatment of severe hyperoxaluria. Liver transplantation (often in addition to renal transplant) may be able to control the disease by correcting the metabolic defect.

In a proportion of patients with primary hyperoxaluria type 1 (about 5%), pyridoxine treatment (vitamin B6) may decrease oxalate excretion and prevent kidney stone formation.

Primary hyperoxaluria is an autosomal recessive disease, meaning both copies of the gene contain the mutation. Both parents must have one copy of this mutated gene to pass it on to their child, but they do not typically show signs or symptoms of the disease.

Diagnosis

Classification

There are three main types of primary hyperoxaluria, each associated with specific metabolic defects. Type 1 is the most common and rapidly progressing form, accounting for about 80% of all cases. Type 2 and 3 account for about approximately 10% each of the population.

Type OMIM Gene
PH1 259900 AGXT
PH2 260000 GRHPR
PH3 613616 HOGA1[1]

Mutations in genes causing PH1 and PH2 result in decreased production or activity of the proteins they make, which stops the normal breakdown of glyoxylate. While mutation in genes causing PH3 results in its overactivity, resulting in excess conversion of hydroxyproline to glyoxylate.[1]

Treatment

Increased water intake and alkalinization of urine is advised to prevent oxalates precipitation in urinary tract. Vitamin B6 (pyridoxine) is used for primary hyperoxaluria type1 as alanine glyoxylate transaminase require pyridoxine as cofactor. A restriction in oxalate intake is of limited use as the main source of oxalate is endogenous.[2]

See also

References
  1. Belostotsky R, Seboun E, Idelson GH, et al. (September 2010). "Mutations in DHDPSL are responsible for primary hyperoxaluria type III". Am. J. Hum. Genet. 87 (3): 392–9. doi:10.1016/j.ajhg.2010.07.023. PMC 2933339. PMID 20797690.
  2. https://iris.unito.it/retrieve/handle/2318/104759/16020/2012_Cochat_post-print.pdf
Classification
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