Mevalonate Kinase Deficiency
Conditions
Keywords
immunoglobulin D, mevalonate kinase, isoprenoids, geranylgeraniol
Brief summary
Mevalonate kinase deficiency (HyperIgD syndrome, HIDS) is an inborn error of immunity caused by a block in the mevalonate pathway. The subsequent lack of isoprenoids with antiinflammatory properties might contribute to the autoinflammatory nature of the disease. A pilot study aims to verify the safety and efficacy of the dietary supplement Geranylgeraniol, aiming at a mitigation of isoprenoids deficiency caused by the above-mentioned block in the MVK pathway.
Detailed description
Mevalonate kinase (MVK) deficiency, a rare autosomal recessive disease, significantly impacts metabolism and immunity, leading to mevalonic aciduria in severe cases and hyper-IgD syndrome (HIDS) in partial deficiency. These conditions arise due to disruptions in the mevalonate pathway, which is an essential metabolic pathway responsible for the synthesis of non-sterol isoprenoids and other molecules. The resulting metabolic blockade triggers autoinflammatory responses, primarily due to deficient isoprenoid intermediates such as geranylgeranyl pyrophosphate (GGPP). This study evaluates the safety and efficacy of dietary geranylgeraniol (GG) supplementation in patients with genetically confirmed mevalonate kinase deficiency. The pilot study consists of a month of a pre-supplementation period to monitor the level of inflammation and clinical status in patients with MVK deficiency(HIDS). This period is followed by 3 months of supplementation of 150mg of GeranylGraniol (GG Pure (Extendlife Natural Products) containing GG gold®30 Annatto Extract, 500 mg capsule (30% geranylgeraniol, 150 mg per capsule).
Interventions
DIETARY_SUPPLEMENTgeranylgeraniol
GG Pure (Extendlife Natural Products) containing GG gold®30 Annatto Extract, 500 mg capsule, use for 3 months, once daily
Sponsors
Washington University School of Medicine
University Hospital, Motol
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Patients with MVK deficiency compared to healthy controls and to subjects on statin therapy (statins target the same metabolic pathway)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients older than 12 years with genetically confirmed MVK deficiency * Overall good clinical status apart from the clinical presentation of the MVK deficiency * Normal liver tests * Compliance with the study protocol
Exclusion criteria
• Children below 12 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in inflammatory parameters | 3 monhts of intervention | Monitoring inflammatory markers before and after intervention - CRP (C reactive protein) and SAA (serum amyloid A) levels will be measured before and after the intervention (time 0 and time 3 months of GG use). These values tend to be elevated in patients with MVK deficiency due to their inflammatory status compared to normal values defined in clinical laboratories (UHMotol CRP \< 8 mg/l, SAA \< 10 mg/l). The expected outcome would result in a decrease in inflammatory markers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the clinical status of patients | 3 months | Monitoring of general clinical status and defined parameters - general condition, fatigue, fever, skin manifestations, abdominal pain, and headache using a questionnaire. The questionnaire is designed for daily monitoring of the parameters mentioned above. The scale of the questionnaire is from 1 to 10, with 1 being the best, normal condition, and 10 being the worst degree of disability. |
Countries
Czechia
Contacts
Primary ContactAnna Šedivá, Prof
Backup ContactEva Aljamal, Mgr
Outcome results
None listed