Table 1.

Clinical spectrum of mevalonate pathway disorders.

Syndrome	Genetic Basis	Clinical Manifestations	Prognosis	References
Mevalonic aciduria (MA)	Mutations in the MVK gene leading to deficiency in cholesterol and isoprenoid biosynthesis	Developmental delays, hypotonia, cerebellar ataxia, peripheral neuropathy, systemic inflammation, neurological complications	Potentially fatal, early diagnosis and comprehensive management essential	(4, 97)
Hyperimmunoglobulinemia D syndrome (HIDS)	Mutations in the MVK gene leading to recurrent but less intense inflammatory episodes	Recurrent fever, lymphadenopathy, gastrointestinal disturbances, skin rash, joint involvement	Generally favourable, normal life expectancy with medical treatment and support	(4, 98)
Phosphomevalonate kinase deficiency (PMKD)	Mutations in PMVK gene, systemic symptoms similar to HIDS	Recurrent fevers, arthritis, rash, abdominal pain, diarrhoea, increased IL-1β secretion	Emerging condition, need for further evaluation in patients with HIDS symptoms	(99–101)
Porokeratosis	Associated with MKD, benign but risk of malignant transformation	Small, slowly enlarging plaques with a raised border, various skin manifestations	Regular dermatological evaluations necessary, monitor for changes	(20, 24, 102)
Macrophage activation syndrome (MAS)	Excessive activation and proliferation of specific immune cells	Widespread inflammation, multiorgan dysfunction	Life-threatening, awareness and prompt recognition crucial	(103–107)