mevalonic aciduria

Mevalonic aciduria, also known as mevalonate kinase deficiency (MKD), is a rare genetic disorder that affects the biosynthesis of cholesterol and isoprenoids.

**Key Features:

Mevalonate kinase deficiency, also known as mevalonic aciduria (MVA), is a rare genetic disorder characterized by recurrent episodes of fever, which typically begin during infancy.

Common signs and symptoms:

• Recurrent episodes of fever, which can last for several days to weeks [1][2]
• Gastro-intestinal symptoms, such as abdominal pain, diarrhea, and vomiting
• Myalgia (muscle pain) and arthralgia (joint pain)
• Skin rash and lymphadenopathy (enlarged lymph nodes)
• Hepatosplenomegaly (enlarged liver and spleen)
• Neurologic symptoms, including:
  • Hypotonia (low muscle tone)
  • Developmental delay
  • Microcephaly (small head size)
  • Cerebellar ataxia (problems with coordination and balance)

Other symptoms:

• Headache
• Skin eruptions
• Pain in various parts of the body

It's worth noting that almost all patients with mevalonic aciduria have elevated excretion of urinary mevalonic acid [5].

Mevalonic aciduria (MVA) is a rare genetic disorder that can be diagnosed through various tests.

Blood and Urine Tests A blood test can show signs of inflammation, which is often present in patients with MVA. A urine test, on the other hand, can detect high levels of mevalonic acid, a key diagnostic hallmark of the condition [2].

Genetic Testing Diagnosing MVA also relies on finding mutations in the MVK gene. In some cases, limiting testing to those with onset of symptoms before age 5 years or to those with joint symptoms may be helpful [7]. However, it's essential to note that enzyme deficiency results in impaired cholesterol biosynthesis and increased production of inflammatory mediators, which can lead to a range of complications [10].

Clinical Trials While not directly related to diagnostic testing, clinical trials have been conducted to evaluate the effectiveness and safety of various treatments for MVA. These trials compare groups receiving different tests or treatments to determine their efficacy [4].

Diagnostic Criteria The exact pathogenesis of MVA is unclear, but enzyme deficiency results in impaired cholesterol biosynthesis and increased production of inflammatory mediators. The diagnostic hallmark is the heightened concentration of mevalonic acid found in urine, plasma, and cerebrospinal fluid, detectable through organic acid analysis [8].

Rare Forms Mevalonate kinase deficiency (MKD) can manifest in rare forms, such as mevalonic aciduria (MVA), which is characterized by dysmorphic features, failure to thrive, psychomotor delay, ocular involvement, and other complications [3][9].

Mevalonic aciduria (MVA) is a rare genetic disorder that affects the body's ability to produce cholesterol and other essential molecules. While there is no cure for MVA, various drug treatments have been explored to manage its symptoms.

Current Treatments

According to recent studies [1], [2], and medical reports [3], the treatment of mevalonic aciduria has largely been nonspecific and ineffective. However, some medications have shown promise in managing the condition's symptoms.

• Cholesterol restriction: While it may seem counterintuitive, restricting cholesterol intake can actually worsen symptoms in MVA patients [4]. This is because the body's ability to produce cholesterol is impaired, leading to a buildup of toxic compounds.
• Lovastatin: This medication, which inhibits the production of cholesterol, has been shown to exacerbate symptoms in some cases [5].
• Interleukin-1 blocking agents: Medications like canakinumab and anakinra have been used to control inflammatory attacks associated with MVA. These drugs work by blocking the action of interleukin-1, a protein that plays a key role in inflammation [6].

Emerging Therapies

Recent research has explored new treatment approaches for mevalonic aciduria.

• Combination therapy: A study published in 2024 found that combining IL-1β blockade with TNFα blockade led to long-term control of both systemic inflammation and colitis in MVA patients [7].
• Allogeneic bone marrow transplantation: In a rare case report, a 3-year-old child with mevalonic aciduria was treated with allogeneic bone marrow transplantation after failing to respond to anakinra and etanercept [8].

Conclusion

While there is no cure for mevalonic aciduria, various drug treatments have been explored to manage its symptoms. Current treatments include interleukin-1 blocking agents, which can help control inflammatory attacks. Emerging therapies, such as combination therapy and allogeneic bone marrow transplantation, hold promise but require further research.

References:

[1] Jeyaratnam et al. (2020) - Canakinumab is the only well-studied and effective treatment for MKD patients with 35% of patients reaching complete remission in a large randomized controlled trial. [2] Bodar et al. (201

Mevalonic aciduria, also known as mevalonate kinase deficiency, has a differential diagnosis that includes other conditions with similar symptoms.

• Behcet's syndrome: This is a form of vasculitis that can cause fever, skin lesions, and joint pain, among other symptoms. [1]
• Systemic arthritis: Mevalonic aciduria can be mistaken for various forms of systemic arthritis, such as rheumatoid arthritis or juvenile idiopathic arthritis, due to the presence of joint pain and inflammation. [2]
• Infections: The recurrent febrile crises associated with mevalonic aciduria can be misattributed to infections, particularly if there is a history of recurrent illnesses. [1]
• AuID (Autoimmune Inflammatory Diseases): Mevalonic aciduria shares some clinical features with AuID, such as fever and lymphadenopathy, making differential diagnosis challenging. [3]

It's essential to note that the presence of mevalonic acid in urine, plasma, and cerebrospinal fluid is a diagnostic hallmark for mevalonic aciduria, distinguishing it from other conditions. [6]