Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

The Clinical Significance of a Single MVK Mutation in HIDS.

Barron2,  Karyl S., Ombrello4,  Amanda K., Goldsmith1,  Donald P., Aksentijevich4,  Ivona, Jones5,  Anne, Barham6,  Beverly K., Kastner3,  Daniel L.

Drexel Univ College Med, Philadelphia, PA
NIAID/NIH, Bethesda, MD
NIAMS, NIH, Bethesda, MD
NIH, NIAMS, Damascus, MD
Ntl Inst of Arthritis & MSK SD, Bethesda, MD


HyperIgD syndrome (HIDS) is an autoinflammatory disorder caused by mutations in the MVK gene that encodes mevalonate kinase. Traditionally it is considered to be transmitted as an autosomal recessive disorder. As a large referral center for children with periodic fever syndromes, we have seen a cohort of symptomatic patients with only 1 mutation in the MVK gene. Since there are no defined diagnostic criteria for HIDS, we compared these patients with our cohort of HIDS patients with 2 MVK mutations.


Patients were evaluated in the Periodic Fever Clinic at the National Institutes of Health. Clinical and laboratory information were collected at each visit. CHI square and Mann-Whitney U tests were performed to compare patients with 2 MVK mutations and those with only 1 MVK mutation.


22 patients with mutations in MVK were evaluated in our clinic; 15 patients were found to have 2 mutations (V377I and 1 other mutation). 7 patients were found to have only 1 mutation, V377I. All MVK coding regions were screened in these patients and we were unable to identify a second mutation. The carrier frequency of V377I in our control Caucasian population was 0.3% (2/739). In contrast, in 344 independent cases of recurrent fever submitted for MVK testing, 8 bore a single copy of V377I for a frequency of 2.3%.

Clinical presentation at the time of a flare was compared between the 2 groups:

 2 mutations1 mutation
Age of onset (mo)5.45.9
Duration (d)5.15.3
Frequency (wks)3.64.5
T max104.8105.1
n (%)n (%) 
Flare with immunizations12/13 (92.3)5/7 (71.4)
Abdominal pain15/15 (100)6/7 (85.7)
Diarrhea14/15 (93.3)6/7 (85.7)
Oral ulcers11/15 (73.3)4/7 (57.1)
Sore throat13/15 (86.7)5/7 (71.4)
Arthralgia13/15 (86.7)5/7 (71.4)
Arthritis4/15 (26.7)2/7 (28.6)
Myalgia8/15 (53.3)5/7 (71.4)
Rash11/15 (73.3)5/7 (71.4)
Cervical adenopathy15/15 (100)6/7 (85.7)
Conjunctivitis7/15 (46.7)1/7 (14.3)
Headache11/14 (78.6)4/6 (66.7)
Developmental delay4/15 (26.7)2/7 (28.6)

There was no significant difference in clinical presentation between the 2 groups of patients.

The two groups were similar in percentage with documented elevations of acute phase reactants with flares and mild elevations of IgA. Mean serum IgD levels for those with 2 MVK mutations was 103 mg/dl vs. 31 mg/dl for those with 1 mutation (p=0.03).


Aside from the higher IgD levels in those children with 2 MVK mutations, there does not appear to be any significant clinical differences between these 2 groups. Prior studies in children with 2 mutations have not correlated IgD levels with disease severity. The relatively small number of children with 1 mutation in our cohort may influence the analyses, but thus far there are no clear trends to offer the clinician in the identification or predictability of the disease course in children with either 1 or 2 mutations. Given the higher frequency of V377I heterozygotes in our patient cohort as opposed to the general population, our data suggests that under some circumstances this could be associated with clinical HIDS, although clearly other factors must play a role given the 0.3% frequency in the general population.

To cite this abstract, please use the following information:
Barron, Karyl S., Ombrello, Amanda K., Goldsmith, Donald P., Aksentijevich, Ivona, Jones, Anne, Barham, Beverly K., et al; The Clinical Significance of a Single MVK Mutation in HIDS. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2105
DOI: 10.1002/art.29870

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