SNP Shot: Genomic Insights

Mevalonate kinase deficiency (MKD) is a genetic disorder characterized by recurring fever episodes, usually starting in infancy. These episodes typically last 3 to 6 days, and their frequency varies among individuals. Fevers tend to occur more frequently in childhood, sometimes up to 25 times per year, but become less frequent as individuals age.

MKD presents with varying signs and symptoms, and its severity depends on the specific type of the condition. There are two main types: the milder hyperimmunoglobulinemia D syndrome (HIDS) and the more severe mevalonic aciduria (MVA).

During fever episodes, individuals with HIDS commonly experience enlarged lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headaches. They may also develop painful sores (aphthous ulcers) in the mouth and, in females, around the vagina. In rare instances, HIDS can lead to amyloidosis, a buildup of protein deposits in the kidneys that can cause kidney failure. Fever episodes in HIDS can be triggered by factors like vaccinations, surgery, injury, or stress. Many individuals with HIDS have elevated levels of immunoglobulin D (IgD) and immunoglobulin A (IgA) in their blood, but the reason for this variability and its effect are not fully understood. Between fever episodes, individuals with HIDS generally show no symptoms and typically have a normal life expectancy.

In contrast to HIDS, individuals with MVA exhibit symptoms constantly, not just during fever episodes. Affected children often have developmental delays, problems with movement and balance (ataxia), recurrent seizures (epilepsy), progressive vision problems, and failure to thrive. People with MVA frequently have an unusually small, elongated head. During childhood or adolescence, eye problems like uveitis (eye inflammation), blue sclera (blue tint to the white of the eye), retinitis pigmentosa (causing vision loss), or cataracts (clouding of the lens) may develop. Affected adults may experience short stature and muscle weakness (myopathy) later in life. During fever episodes, individuals with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. The severity of MVA varies greatly; severely affected children may only live into early childhood, while mildly affected individuals can have a normal life expectancy.

Inheritance:

MKD is inherited in an autosomal recessive manner. This means that an individual must inherit a mutated copy of the gene from both parents to develop the condition. The parents, who each carry one copy of the mutated gene, are typically asymptomatic.