Table 4. [Haploinsufficiency of A20: Recommended Evaluations Following Initial Diagnosis]. - GeneReviews®

System/Concern	Evaluation	Comment
Rheumatologic	History & physical exam for signs/symptoms of systemic inflammation, fevers, serositis/pain, & joint involvement	Consider referral to rheumatologist to initiate biologic therapies (see Treatment of Manifestations).
Assessment of inflammatory markers (serum CRP & ESR), CBC w/differential, & autoantibody titers (ANA, ANCA, CCP3, RF)	Imaging of abdomen to assess for splenomegaly &/or hepatomegaly should also be considered if there are findings of or suspected spleen or liver enlargement on physical exam.
Immunologic	Assessment for immune dysfunction or immunodeficiency	Quantitative blood immunoglobulins (IgG, IgA, IgM) Vaccine-specific responses (tetanus, diphtheria) T/B/NK cell counts
Skin	Full skin exam	To assess for rashes Consider dermatology consultation for mgmt.
Eye	Ophthalmologic eval	For possible reduced vision, ptosis, abnormal eye movements, uveitis, retinal infarcts, &/or optic nerve damage
Kidney	Kidney function tests & urinalysis for proteinuria	If nephritis is suspected, consultation w/nephrologist is recommended.
Consultation w/nephrologist	If there are signs/symptoms of renal involvement
Gastrointestinal	Fecal calprotectin to assess for inflammatory bowel disease	Referral to gastroenterologist for endoscopy, enteroscopy, &/or colonoscopy Can consider imaging (CT, ultrasound, MR enterography)
Liver	Transaminases (AST & ALT) & abdominal (liver) ultrasound	Referral to hepatologist if AST/ALT are elevated &/or liver ultrasound is abnormal
Cardiac	Consider echocardiogram to assess for pericarditis or cardiac involvement.	If coronary vasculitis/vasculopathy &/or AA amyloidosis are suspected, consider referral to cardiologist for noninvasive or direct angiography.
Hematologic	Hematologic eval	When cytopenias are detected on CBC, perform bone marrow biopsy. Assess for hemolysis, reticulocyte count. Measure antiplatelet antibodies.
Endocrinologic	Thyroid function tests Assess for diabetes: obtain fasting blood glucose concentration & consider oral glucose tolerance test or hemoglobin A1c.	Consider endocrinologist referral if abnormal.
Neurologic	Possible CNS involvement: consider MRI w/MRA & MRV (noninvasive angiography) or DSA (direct angiography) if CNS vasculitis is suspected. Possible aseptic meningitis: lumbar puncture w/cell counts / protein / glucose concentration & bacterial/viral cultures Possible peripheral nerve involvement: consider referral to neurologist for EMG &/or nerve biopsy if mononeuritis or vasculitic neuropathy is suspected.	Consider referral to neurologist. Diagnosis of vasculitic neuropathy requires treatment w/escalating immunomodulators to prevent permanent nerve damage.
Genetic counseling	By genetics professionals	To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of HA20 to facilitate medical & personal decision making (e.g., predictive testing of at-risk family members; see Evaluation of Relatives at Risk).
Family support & resources	By clinicians, wider care team, & family support organizations	Assessment of family & social structure to determine need for: Community or online resources such as Parent to Parent Social work involvement for parental support Home nursing referral

System/Concern

Evaluation

Comment

Rheumatologic

History & physical exam for signs/symptoms of systemic inflammation, fevers, serositis/pain, & joint involvement

Consider referral to rheumatologist to initiate biologic therapies (see Treatment of Manifestations).

Assessment of inflammatory markers (serum CRP & ESR), CBC w/differential, & autoantibody titers (ANA, ANCA, CCP3, RF)

Imaging of abdomen to assess for splenomegaly &/or hepatomegaly should also be considered if there are findings of or suspected spleen or liver enlargement on physical exam.

Immunologic

Assessment for immune dysfunction or immunodeficiency

Quantitative blood immunoglobulins (IgG, IgA, IgM)
Vaccine-specific responses (tetanus, diphtheria)
T/B/NK cell counts

Skin

Full skin exam

To assess for rashes
Consider dermatology consultation for mgmt.

Eye

Ophthalmologic eval

For possible reduced vision, ptosis, abnormal eye movements, uveitis, retinal infarcts, &/or optic nerve damage

Kidney

Kidney function tests & urinalysis for proteinuria

If nephritis is suspected, consultation w/nephrologist is recommended.

Consultation w/nephrologist

If there are signs/symptoms of renal involvement

Gastrointestinal

Fecal calprotectin to assess for inflammatory bowel disease

Referral to gastroenterologist for endoscopy, enteroscopy, &/or colonoscopy
Can consider imaging (CT, ultrasound, MR enterography)

Liver

Transaminases (AST & ALT) & abdominal (liver) ultrasound

Referral to hepatologist if AST/ALT are elevated &/or liver ultrasound is abnormal

Cardiac

Consider echocardiogram to assess for pericarditis or cardiac involvement.

If coronary vasculitis/vasculopathy &/or AA amyloidosis are suspected, consider referral to cardiologist for noninvasive or direct angiography.

Hematologic

Hematologic eval

When cytopenias are detected on CBC, perform bone marrow biopsy.
Assess for hemolysis, reticulocyte count.
Measure antiplatelet antibodies.

Endocrinologic

Thyroid function tests
Assess for diabetes: obtain fasting blood glucose concentration & consider oral glucose tolerance test or hemoglobin A1c.

Consider endocrinologist referral if abnormal.

Neurologic

Possible CNS involvement: consider MRI w/MRA & MRV (noninvasive angiography) or DSA (direct angiography) if CNS vasculitis is suspected.
Possible aseptic meningitis: lumbar puncture w/cell counts / protein / glucose concentration & bacterial/viral cultures
Possible peripheral nerve involvement: consider referral to neurologist for EMG &/or nerve biopsy if mononeuritis or vasculitic neuropathy is suspected.

Consider referral to neurologist.
Diagnosis of vasculitic neuropathy requires treatment w/escalating immunomodulators to prevent permanent nerve damage.

Genetic
counseling

By genetics professionals

To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of HA20 to facilitate medical & personal decision making (e.g., predictive testing of at-risk family members; see Evaluation of Relatives at Risk).

Family support
& resources

By clinicians, wider care team, & family support organizations

Assessment of family & social structure to determine need for:

Community or online resources such as Parent to Parent
Social work involvement for parental support
Home nursing referral

From: Haploinsufficiency of A20

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

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