Disease name: Primary hyperoxaluria

ICD-10 Disease Code: E72.53 - Primary hyperoxaluria

ICD-10 Disease Group: E72 - Other disorders of amino-acid metabolism

Primary hyperoxaluria (PH) is a rare genetic disorder that leads to recurrent kidney and bladder stones, often progressing to end-stage renal disease (ESRD). PH impairs the kidneys' ability to filter fluids and waste and can be life-threatening. The disorder is caused by an overproduction of oxalate, which is normally excreted in urine. Excess oxalate combines with calcium to form kidney and bladder stones, damaging the kidneys and other organs, and causing symptoms such as blood in the urine and urinary tract infections (UTIs). As kidney function declines, oxalate accumulates in the body (systemic oxalosis), leading to several possible complications, including bone fractures. 

There are three types of primary hyperoxaluria, each varying in severity and genetic cause. Type 1 usually presents in childhood to early adulthood and can lead to ESRD at any age. Type 2 is similar but with later onset of ESRD, while Type 3 typically begins in early childhood, although its full pathobiology is not well understood.

The genes involved in disease onset encode enzymes responsible for the breakdown of amino acids and other compounds. The HOGA1 gene produces an enzyme involved in breaking down an amino acid, hydroxyproline, resulting in the formation of glyoxylate. This glyoxylate is further processed by enzymes encoded by the AGXT and GRHPR genes. Mutations in thesegenes reduce the production or activity of enzymes, leading to the improper breakdown of glyoxylate. As a result, glyoxylate accumulates and is converted into oxalate. Excess oxalate, when not excreted, combines with calcium to form deposits that can damage the kidneys and other organs.

Mutations in the AGXT, GRHPR, and HOGA1 genes are responsible for PH types 1, 2, and 3, respectively.

Primary hyperoxaluria is estimated to affect 1 in 58,000 individuals worldwide, with type 1 accounting for around 80% of cases.

Hyperoxaluria can lead to kidney stones, nephrocalcinosis, and eventually renal failure and systemic oxalosis. Symptoms can appear at any age, ranging from severe infantile failure to thrive and cortical nephrocalcinosis with renal failure, to milder cases that involve haematuria, medullary nephrocalcinosis, or sporadic kidney stones, even within the same family. PH1 is the most severe form, with over 70% of patients developing end-stage kidney disease, including those with sporadic kidney stones. In severe renal failure, oxalate accumulates in various tissues, affecting bones, eyes, heart, arteries, and peripheral nerves (systemic oxalosis). PH2 follows a milder course, with no cases of infantile oxalosis and about 20% of patients developing end-stage kidney disease later in life. PH3 is the least severe subtype, with very few cases of renal impairment and no reports of end-stage kidney disease.

Treatment for PH is tailored to the specific symptoms and requires a multidisciplinary approach, involving specialists such as nephrologists, hepatologists, and urologists. Key treatments include high fluid intake, pyridoxine (vitamin B6) supplementation, and medications such as potassium citrate to reduce stone formation. In severe cases, particularly when kidney function declines, liver or combined liver-kidney transplants may be necessary. Dialysis can manage oxalate levels temporarily but is not a long-term solution. Recently, gene therapy options including Lumasiran (Oxlumo) and nedosiran (Rivfloza) have emerged, offering new treatment avenues by lowering urinary oxalate levels in PH type I patients.

• https://www.icd10data.com/
• https://www.orpha.net/consor/cgi-bin/index.php
• https://rarediseases.org/
• https://medlineplus.gov/genetics/
• https://www.cdc.gov/

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Primary hyperoxaluria (PH)