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Table 1 Summary of demographic and clinical characteristics of patients with MKD

From: Natural history of mevalonate kinase deficiency: a literature review

Author van der Hilst et al. [8] Bader-Meunier et al. [2] Doglio et al. [9] Jeyaratnam et al. [17], Toplak et al. [10]a, Ter Haar et al. [5]b
Study International HIDS Database France/Belgium Italy International Eurofever Registry
Study design Retrospective follow-up Retrospective follow-up Prospective follow-up Retrospective follow-up
Study period 1994–2007 1999–2010 N/A 2009–2011a
Length of follow-up, years 14 Not specified Long-term (not specified) 11.5
Number of patients 103 HIDS 50 MKD 56 MKD 114 MKD
Most common MVK mutation (allele frequency in patients) p.Val377Ile (50 %) p.Val377Ile (43 %) p.Val377Ile (47 %) p.Val377Ile (48 %)
2nd most common MVK mutation (allele frequency in patients) p.Ile268Thr (15 %) p.Ile268Thr (8 %) N/A p.Ile268Thr (13 %)
Age of patients, years, median or mean ± SD (range) 19 (2, 74) 19.5 (0.6, 58) at last visit 13.3 ± 8.5 at follow-up 14a (1, 60)a
% of patients aged <18 years N/A N/A N/A 63 %a
Age at onset of symptoms, months, median or mean ± SD (range) 6 (0, 120) 4 (1 day, 240 months) 10.5 ± 15.3 (1, 108) 6 (~0, ~72)a
% of patients who had the first attack within the first year of life 78 % N/A N/A 71 %b
% of patients who had the first attack before the age of 5 years N/A 92 % N/A N/A
Age at diagnosis, years, median (range) 10 (<3 months, 52 years) N/A N/A ~8a (~3 months, ~29 years)a
Duration from onset to diagnosis, years, median (range) 9.9 N/A N/A 2.5a (0.1–8.3)a
Disease duration, years, mean ± SD (range) N/A 24 (1, 55) from the onset to most recent assessment 12.4 ± 8.7 13.1b at enrollment
Sex, % of men 50 % 42 % 52 % 46 %
Ethnicity N/A White, 69 % N/A Caucasian, 90 %
Positive family history, % N/A N/A N/A 26 %a
% of patients with >12 fever episodes/year 44 %, aged 0–10 year
24 %, aged 11–20 year
18 %, aged >20 year
76 % at the onset N/A N/A
Number of fever episodes per year, mean ± SD (min, max) or median N/A N/A 13.8 ± 5.4 (3, 30) at baseline
8.8 ± 6.7 at follow-up
12
Duration of fever episodes, days, mean (range) or median N/A 3.7 (1, 10) N/A 5 (3 to 7 in 81 % of the patients)b
Precipitating factors of fever episodes, %    N/A  
 Vaccination 63 % for the 1st attack N/A   36 %
 Infection N/A N/A   17 %
 Infection and/or vaccination N/A 42 %   N/A
 Stress Many cases (not specified) N/A   24 %
Signs and symptoms during febrile attacks, %   Estimated % Estimated % N/A  
Gastrointestinal/abdominal   Onset Cumulative   
 Abdominal pain 85 % 20 % 63 %   88 %
 Diarrhea 72 % 40 % 69 %   84 %
 Vomiting 71 % 11 % 45 %   69 %
 Hepatomegaly 22 % 25 % 37 %   N/A
 Serositis 19 % N/A N/A   N/A
 Pericarditis N/A 0 % 4 %   N/A
Lymphoid tissue      
 Lymphadenopathy 87 % 38 % 71 %   84 %b
 Splenomegaly 32 % 32 % 63 %   N/A
Musculoskeletal      
 Arthralgia 84 % 20 % 67 %   71 %
 Arthritis 55 % 6 % 43 %   28 %
 Myalgia N/A 0 % 22 %   57 %
Cutaneous and mucocutaneous      
 Skin lesions or maculopapular rash 69 % 43 % 67 %   39 %
 Aphthous ulcers or stomatitis 49 % 15 % 43 %   60 %
 Pharyngitis N/A N/A N/A   28 %
General      
 Cold chills 63 % N/A N/A   N/A
 Headache 63 % 0 % 12 %   38 %
 Malaise N/A N/A N/A   65 %
 Weight loss N/A N/A N/A   66 %
 Fatigue N/A N/A N/A   63 %
 Mood disorders N/A N/A N/A   24 %
 Thrombocytopenia N/A 4 % 4 %   N/A
 Macrophage activation syndrome N/A 0 % 6 %   1 %
Associated long-term conditions, %     N/A  
 AA amyloidosis 3 % 0 %   5 %
 Abdominal adhesions 10 % 6 %   N/A
 Joint contractures 4 % N/A   N/A
 Recurrent and/or severe infections N/A 27 %   N/A
 Severe pneumococcal infections 1 % 6 %   N/A
 Hypogammaglobulinemia N/A 6 %   N/A
 Renal angiomyolipoma N/A 6 %   N/A
 Cerebellar syndrome N/A N/A   3 %
 Seizures N/A N/A   5 %
 Mental retardation N/A 2 %   4 %
 Chronic neurologic, abdominal, renal, pulmonary, endocrine, cutaneous, ocular, or hematologic involvement, erosive polyarthritis, and/or Sjögren’s syndrome N/A 55 %   N/A
Biomarkers, median (range), % of the patients above the upper limit of the [normal value]    N/A  
 WBC count, x109/L during fever episodes [4–8] 15, ↑ in 100 % of the patients 18 (7.5–59)   ↑ in 66 % of tested patients
 CRP, mg/L during fever episodes [<5] 163 (36–404), ↑ in 100 % of the patients 157 (47–440), ↑ in 100 % of tested patients   ↑ in 94 % of tested patients
 ESR mm/hour during fever episodes [<10] 76, ↑ in 100 % of the patients 64 (27–120), ↑ in 100 % of tested patients   ↑ in 98 % of tested patients
 IgA, g/L [0.5–3.4] 4.1, 64 % of tested patients >2.6 g/L 4.8 (0.25–20.9), 57 % of tested patients >3 g/L   N/A
 IgD, IU/mL [<100] 400 (<0.8-5300), ↑ in 78 % of the patients 760 (0–2500), ↑ in 88 % of tested patients   ↑ in 72 % of tested patients
 Urinary mevalonic acid, mmol/mol creatinine during fever episodes [<1] N/A 17 (2.8–10000), ↑ in 100 % of tested patients   ↑ in 93 % of tested patients
Biomarkers, median (range), % of the patients below the limit of the [normal value]     
 MVK activity, % of control cells [>25] N/A 2.6 (0–24), ↓ in 100 % of tested patients N/A N/A
  1. Abbreviations: CRP C-reactive protein, ESR erythrocyte sedimentation rate, HIDS hyperimmunoglobulinemia D syndrome, IgA immunoglobulin A, IgD immunoglobulin D, MKD mevalonate kinase deficiency, MVK mevalonate kinase, N/A data not available, WBC white blood cell
  2. aFrom the Eurofever registry by Toplak et al. [10] with 104 MKD patients
  3. bFrom the Eurofever registry by Ter Haar et al. [5] with 85 MKD patients