Pathophysiology
It is not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathway, the prenylation chains (geranylgeraniol and farnesol) might play a role. Diagnosis
Mevalonate kinase deficiency causes an accumulation of mevalonic acid in the urine, resulting from insufficient activity of the enzyme mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36). The disorder was first described in 1985.Classified as an inborn error of metabolism, mevalonate kinase deficiency usually results in developmental delay, hypotonia, anemia, hepatosplenomegaly, various dysmorphic features, mental retardation, an overall failure to thrive and several other features. Treatment
There is no treatment for MKD. But, the inflammation and the other effects can be reduced to a certain extent. IL-1 targeting drugs can be used to reduce the effects of the disorder. Anakinra is antagonist to IL-1 receptors. Anakinra binds the IL-1 receptor, preventing the actions of both IL-1α and IL-1β, and it has been proved to reduce the clinical and biochemical inflammation in MKD. It can effectively decreases the frequency as well as the severity of inflammatory attacks when used on a daily basis. Disadvantages with the usage of this drug are occurrence of painful injection site reaction and as the drug is discontinued in the near future the febrile attacks start. (Examined in a 12-year-old patient). Canakinumab is a long acting monoclonal antibody which is directed against IL-1β has shown to be effective in reducing both frequency and severity in patients with mild and severe MKD in case reports and observational case series.
Diagnosis
Although it is listed in the ICD-9 (306.2) and ICD-10 (F45.8) under "somatoform autonomic dysfunction", the term is no longer in common use by any medical agencies and has generally been superseded by more specific diagnoses. The orthostatic intolerance observed by Da Costa has since also been found in patients diagnosed with chronic fatigue syndrome, postural orthostatic tachycardia syndrome (POTS) and mitral valve prolapse syndrome. In the 21st century, this intolerance is classified as a neurological condition. Exercise intolerance has since been found in many organic diseases. Classification
There are many names for the syndrome, which has variously been called soldiers heart, cardiac neurosis, chronic asthenia, effort syndrome, functional cardiovascular disease, neurocirculatory asthenia, primary neurasthenia, and subacute asthenia. Da Costa himself called it irritable heart  and the term soldiers heart was in common use both before and after his paper. Most authors use these terms interchangeably, but some authors draw a distinction between the different manifestations of this condition, preferring to use different labels to highlight the predominance of psychiatric or non-psychiatric complaints. For example, Oglesby Paul writes that "Not all patients with neurocirculatory asthenia have a cardiac neurosis, and not all patients with cardiac neurosis have neurocirculatory asthenia." None of these terms have widespread use. Treatment
The report of Da Costa shows that patients recovered from the more severe symptoms when removed from the strenuous activity or sustained lifestyle that caused them.