HRPT-related hyperuricemia

HRPT-related Hyperuricemia: A Metabolic Disorder

HRPT-related hyperuricemia, also known as Kelley-Seegmiller syndrome, is a rare X-linked metabolic disorder caused by a mutation in the HPRT1 gene [4]. This condition presents as a hyperuricemia characterized by excessive purine production often resulting in renal stones, uric acid nephropathy, and renal obstruction [7][9].

Key Features:

• Elevated serum uric acid concentrations in both extracellular fluids and tissues
• Impaired uric acid excretion
• Renal stones, uric acid nephropathy, and renal obstruction are common complications
• Can be associated with neurological symptoms in some cases

Subtypes:

• Lesch-Nyhan syndrome (LNS): a severe form of the disorder characterized by complete deficiency of HPRT residual activity [1]
• Kelley-Seegmiller syndrome: a milder form of the disorder caused by partial deficiency of HPRT residual activity, typically greater than 8% [1][5]

Prevalence and Impact:

• Estimated to affect approximately 15% of HPRT deficient patients [5]
• Can have significant impact on quality of life due to associated complications

References:

[1] Virtually complete deficiency of HPRT residual activity is associated with the Lesch-Nyhan syndrome (LNS; 300322), whereas partial deficiency (at least 8%) is associated with the Kelley-Seegmiller syndrome.

[4] Hyperuricemia, hprt-related is an X-linked metabolic disorder caused by a mutation in the HPRT1 gene. It presents as Lesch-Nyhan syndrome (LNS) with severe neurological symptoms and renal complications.

[7] HRPT-related hyperuricemia. Definition: A hyperuricemia characterized by excessive purine production often resulting in renal stones, uric acid nephropathy, and renal obstruction that ...

[9] HRPT-related hyperuricemia. Definition, A hyperuricemia characterized by excessive purine production often resulting in renal stones, uric acid nephropathy ...

Similarities to HND and Additional Information

HRPT-related hyperuricemia (HRH) shares some similarities with HPRT deficiency, but without clinically obvious neurologic deficits [1]. However, it's essential to note that the symptoms can vary depending on the individual.

Common Symptoms

The common symptoms of HRH include:

• Impaired kidney function
• Acute gouty arthritis
• Self-mutilating behaviors such as lip and finger biting
• Urolithiasis (kidney stones)
• Uric acid nephropathy
• Urinary infections
• Renal obstruction

These symptoms can occur in both males and females, although the severity may differ [6].

Additional Information

It's worth noting that HRH is a rare metabolic disorder caused by mutations in the HPRT gene. This condition leads to an overproduction of uric acid, which can cause various health problems.

References:

• [1] HA Jinnah · 2020 · Cited by 20 — HPRT1-Related Hyperuricemia (HRH)
• [6] by E Kostalova · 2015 · Cited by 106 — X-linked HPRT deficiency may present as hyperuricemia and/or gout in both male and female carriers.

Diagnostic Testing for HPRT1-related Hyperuricemia

HPRT1-related hyperuricemia can be diagnosed through various tests, which are essential for identifying the condition and developing an effective treatment plan.

• Measurement of HPRT enzyme activity: This is a definitive diagnostic test that measures the level of HPRT enzyme in blood or tissue samples [3]. Blood samples are often used, but DNA from whole blood can also be analyzed.
• Biochemical tests: These tests measure the levels of uric acid and other related compounds in the body. Elevated serum uric acid levels are a hallmark of HPRT1-related hyperuricemia [5].
• Enzymatic tests: These tests assess the activity of the HPRT enzyme, which is essential for breaking down purines and preventing their accumulation in the body.
• Molecular tests: Genetic testing can identify mutations in the HPRT1 gene that cause the condition.

Additional Diagnostic Criteria

The diagnosis of HPRT1-related hyperuricemia may also be suspected based on clinical manifestations such as:

• Nephrolithiasis (kidney stones)
• Obstructive nephropathy
• Hyperuricemia and hyperuricosuria (elevated uric acid levels in the blood and urine)

Genotype-Phenotype Studies

Studies have shown that genotype-phenotype correlations can be useful in predicting the severity of HPRT1-related hyperuricemia [4]. These studies involve analyzing the genetic mutations associated with the condition to determine their impact on enzyme activity and disease severity.

References

[3] Jul 25, 2024 — Definitive diagnosis is obtained most often by measurement of HPRT enzyme activity in blood or tissue. Blood

Treatment Options for Hyperuricemia Associated with Hypophosphatemic Rickets of Infancy (HRPT)

Hyperuricemia is a common complication in patients with HRPT, and effective management is crucial to prevent associated health issues. The primary goal of treatment is to reduce serum uric acid levels and alleviate symptoms.

Allopurinol: A First-Line Treatment

Allopurinol, an xanthine oxidase inhibitor, is often the first-line treatment for hyperuricemia in HRPT patients [1]. This medication works by inhibiting the enzyme responsible for converting hypoxanthine to uric acid, thereby reducing serum uric acid levels. Allopurinol has been shown to be effective and generally safe for treating uric acid overproduction in patients with HPRT deficiency [2].

Uricosuric Agents

In some cases, uricosuric agents may be used in conjunction with allopurinol or as an alternative treatment option. These medications increase renal excretion of uric acid, helping to lower serum levels [3]. However, the choice between xanthine oxidase inhibitors and uricosuric medicines is based on individual patient factors, such as urinary uric acid levels.

Monitoring and Adjustments

Regular monitoring of serum uric acid levels and adjustments to treatment plans are essential to ensure effective management. Healthcare providers should closely monitor patients for signs of adverse effects or inadequate response to therapy [4].

References:

[1] Torres RJ (2007) - Allopurinol efficacy and safety in treating uric acid overproduction in HPRT deficiency patients. [2] Ronda L (2017) - Restoration of uricolysis through enzyme therapy for severe hyperuricemia caused by HPRT deficiency. [3] SOFS URATE (Cited by 15) - Drugs that inhibit xanthine oxidase and uricosuric agents for treating hyperuricemia. [4] NORD (Lesch Nyhan Syndrome guidelines) - Recommendations for managing hyper

Differential Diagnosis of HPRT-related Hyperuricemia

HPRT (Hypoxanthine-Guanine Phosphoribosyltransferase) deficiency is a genetic disorder that can lead to the overproduction of uric acid, resulting in hyperuricemia. When diagnosing HPRT-related hyperuricemia, it's essential to consider other possible causes of elevated uric acid levels.

Possible Differential Diagnoses:

• Glucose 6-phosphate dehydrogenase (G6PD) deficiency [2]
• Lesch-Nyhan syndrome [7][13]
• Nephrolithiasis and obstructive uropathy [14]

These conditions can present with similar symptoms, such as hyperuricemia, nephrolithiasis, and gouty arthritis. A comprehensive diagnostic workup is necessary to rule out these differential diagnoses.

Key Diagnostic Considerations:

• HPRT enzyme activity measurement in live cells (e.g., cultured fibroblasts) [8]
• Molecular genetic techniques for confirmation of HPRT deficiency [8]

A multidisciplinary approach, involving experts from various fields, is crucial for accurate diagnosis and management of HPRT-related hyperuricemia.

References:

[1] Mishima E. (2020). Familial juvenile gout and HPRT deficiency. Cited by 7.

[2] Kostalova E. (2015). X-linked HPRT deficiency presenting as hyperuricemia and/or gout in both male and female carriers. Cited by 106.

[3] Torres RJ. (2007). Partial HPRT deficiency: A review of the literature. Cited by 447.

[4] Laróvere LE. (2021). Males with developmental delay, neurological and behavioral problems, and hyperuricemia could be affected by HPRT deficiency with severe phenotype; the importance of early diagnosis.

[5] Jul 25, 2024 - The overproduction of uric acid is associated with hyperuricemia.

[6] Jul 17, 2022 - Lesch-Nyhan syndrome is an extremely rare metabolic disorder that occurs before birth, mostly in boys.

[7] Jan 7, 2022 - Diagnosis is based on HPRT enzyme activity, preferably measured in live cells such as cultured fibroblasts.

[8] Our unusual findings expand the differential diagnosis of hyperuricemia and gout in females.