Primary hyperoxaluria is a rare condition, resulting in increased excretion of oxalate, with oxalate stones being common.
Signs/symptoms
Pathophysiology
The buildup of oxalate in the body causes increased renal excretion of oxalate, which in turn results in renal and bladder stones. Stones cause urinary obstruction, secondary infection of urine and eventually kidney damage. Oxalate stones in primary hyperoxaluria tend to be severe, resulting in relatively early kidney damage, which impairs the excretion of oxalate leading to a further acceleration in accumulation of oxalate in the body. After the development of kidney 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. Kidney failure is a serious complication requiring treatment in its own right. Dialysis can control kidney 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 may be able to control the disease by correcting the metabolic defect. In a proportion of patients with primary hyperoxaluria type 1, pyridoxine treatment may decrease oxalate excretion and preventkidney 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
AGXT
PH2
GRHPR
PH3
HOGA1
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.
Treatment
Increased water intake and alkalinization of urine is advised to prevent oxalates precipitation in urinary tract. Vitamin B6 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.
