Mevalonate kinase deficiency
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy.
Overview
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood, the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older, the episodes occur less often.
There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA).
Symptoms
Hyperimmunoglobulinemia D syndrome (HIDS)
During episodes of fever, people with HIDS typically experience:
- Enlargement of the lymph nodes (lymphadenopathy)
- Abdominal pain
- Joint pain
- Diarrhea
- Skin rashes
- Headache
- Painful sores called aphthous ulcers around the mouth or, in females, around the vagina
Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. Individuals with HIDS do not have symptoms between fever episodes and typically have a normal life expectancy.
Mevalonic aciduria (MVA)
People with MVA have symptoms at all times. Features include:
- Developmental delay
- Problems with movement and balance (ataxia)
- Recurrent seizures (epilepsy)
- Progressive problems with vision
- Failure to gain weight and grow at the expected rate (failure to thrive)
- Unusually small, elongated head
- Eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), or retinitis pigmentosa
- Clouding of the lens of the eye (cataracts)
- Muscle weakness (myopathy) in adults
- Short stature in adults
During fever episodes, people with MVA may also experience an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes.
Causes
Mutations in the MVK gene cause mevalonate kinase deficiency. This gene provides instructions for making the mevalonate kinase enzyme, which is involved in the production of cholesterol, steroid hormones, and bile acids. It also helps produce substances necessary for cellular functions, such as cell growth, maturation, and the formation of the cytoskeleton.
Most MVK mutations result in an unstable enzyme, leading to a reduction in enzyme activity. The severity of the condition is determined by the level of enzyme activity:
- HIDS: Approximately 1 to 20 percent of normal activity.
- MVA: Less than 1 percent of normal activity.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an affected individual each carry one copy of the mutated gene but typically do not show signs of the condition.