Mevalonate Kinase Deficiency-mild/moderate, Hyperimmunoglobulinemia D with Periodic Fever Syndrome

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Acronym:
MKD-mild/moderate (aka HIDS)

SAID group:
Mevalonate Kinase Deficiency (MKD)

Gene:
MVK

Inheritance:
Autosomal recessive. Some cases with only one mutation found. [33]

Ethnicity:
Mostly of Dutch descent, or Northern European. [1]

Frequency:
Unknown, but very rare. >200-300 known patients worldwide, (>300, when suspected cases are also included.) [12]

Timing of symptoms:
3-7 days duration. Recurrent bouts of fever and flares every 2-12 weeks. [1] [9] Some flares occur after vaccines. [9]

Age of onset:
>90% present with symptoms in infancy. [9]

Skin cutaneous:
Diffuse maculopapular rash. Polymorphous rashes. Some with petechiae or purpura present. [1], [9] 50% with apthous ulcers or genital ulcers. [130] Porokeratosis of Mibelli in one patient, and disseminated superficial actinic porokeratosis (DSAP) in a few cases of patients of Asian ancestry. [136]

Neurologic:
Headaches and fevers with flares of symptoms are common. [1] [9] More severe neurological symptoms are rarely present in HIDS. [9]

Auditory:
Uncommon – not believed to be caused by HIDS. [1] [9]

Ophthalamic:
Uncommon. [9] Some with conjunctivitis. [134] and there are a few patients with retinitis pigmentosa (RP). [136]

Cardiopulmonary:
Rare. [1] Some patients have developed severe respiratory infections. Higher risk for issues with S. pneumoniae infections. [78]

Abdominal:
Extreme pain, vomiting and diarrhea with flares. [1], [9] A few cases with colitis, including early-onset, and sometimes severe colitis in the neonatal period, with bloody diarrhea. [136]. Some with hepatomegaly, splenomegaly, hepatosplenomegaly, or other gastrointestinal issues. [78]

Lymphatic:
Cervical lymphadenopathy with flares. [1] A few with splenomegaly. [78] A few patients have had macrophage activation syndrome (MAS.) [136]

Joints bones muscles cartilage:
Arthralgias are common, symmetric polyarthritis is frequently noted. [1]

Vasculitis:
Cutaneous vasculitis is common. Henoch-Schönlein purpura (HSP) is rare. [1]

Amyloidosis:
<5-10% – uncommon. [9]

Abnormal labs:
High: ESR, CRP, SAA with flares. Mevalonate aciduria noted during flares. [1] High IgD with IgA in 80% patients. IgD may be normal in infants and young children with HIDS. Note that there are other conditions where IgD may sometimes be elevated, (see also FMF, TRAPS, PFAPA on our chart) so this is not considered the most accurate diagnostic lab for MVK diseases.

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