Autoinflammatory Diseases 5%

Question 1

FMF disease causing genetic variants are so common in certain populations due to a protective advantage to what organism?

Answer 1

Yersina species, including Y. pestis

Question 2

A 7-year-old male presents with episodic fever lasting 14-21 days at a time. During the episodes, he has periorbital edema with conjunctivitis, a migratory rash that goes from proximal to distal and appears annular or serpiginous, scrotal edema, chest pain, abdominal pain that mimcs acute abdomen, and diarrhea, L knee pain but no arthritis that happens a few times a year. What is the first line treatment?

Answer 2

Anti-TNF (etanercept) for TNF Receptor Associated Periodic Syndrome (TRAPS)
Prednisone taper for mild, infrequent episodes

Infliximab may lead to flare
Colchicine does not work

Distinguishing features of TRAPS:
Longer duration 1-4+ weeks (more than 7 days)
Periorbital edema, conjunctivitis seen during flares - specific to TRAPS
Migratory proximal to distal erythematous rash
Peritoneal inflammation can lead to adhesions

Question 3

Which periodic fever syndrome can cause abdominal adhesions?

Answer 3

TNF Receptor Associated Periodic Syndrome (TRAPS)

Question 4

You check baseline labs in between a TRAPS flare. What labs may still be abnormal?

Answer 4

Acute phase reactants remain elevated between clinical attacks, suggesting elevated level of baseline inflammation

Question 5

What mutation is associated with TRAPS?

Answer 5

TNFRSF1A

Question 6

What are complications of TRAPS?

Answer 6

Systemic amyloidosis

Renal failure from renal amyloidosis

Question 7

What is the differential diagnosis for TRAPS?

Answer 7

Recurrent viral infections
Immunodeficiency: FTT, unusual or opportunistic infections
Anatomical defect: frequent localization of infection to same organ
Acute abdomen

Question 8

What is the mode of inheritance of the mutation in TNFRSF1A that results in TRAPS?

Answer 8

Autosomal dominant, gain of function mutation

Question 9

A 4-year-old male has episodic fever lasting 12 hours-3 days with chest pain, abdominal pain with constipation, body aches, knee and wrist swelling, and erysipeloid rash on foot and ankle. The onset of symptoms seems unpredictable. What is the first line treatment?

Answer 9

Colchicine for Familial Mediterranean Fever - suppresses pyrin inflammasome

Question 10

What can trigger FMF flares?

Answer 10

Stress, menstruation

Question 11

What percentage of patients have a heterozygous mutation in a pathogenic variant of MEFV?

Answer 11

30%

Question 12

What class of medication can be used in FMF refractory to colchicine?

Answer 12

IL-1 blockade: anakinra, canakinumab, rilonacept

Question 13

In patients with FMF, what conditions occur with increased frequency?

Answer 13

Behcet disease,
Polyarteritis nodosa, 
Microscopic polyangiitis, 
Glomerulonephritis, 
HSP

Question 14

In patients with FMF, what is an independent risk factor for Behcet disease and ankylosing spondylitis?

Answer 14

M694V mutation in MEFV

Question 15

An adult with a history of periodic fever syndrome presents with renal failure. A renal biopsy is obtained. What is a unique histologic finding that can be seen on renal biopsy?

Answer 15

Serum amyloidosis will have apple-green birefringence on biopsy

Question 16

What is the differential diagnosis for FMF?

Answer 16

Recurrent viral infections
Immunodeficiency: FTT, unusual or opportunistic infections
Anatomical defect: frequent localization of infection to same organ
Acute appendicitis
Colchicine-induced myopathy
- Fever, high ESR, normal CK, and EMG with inflammatory myopathy helps rules out

Question 17

What populations have the highest frequency of FMF?

Answer 17

Most frequently affects Sephardi and Ashkenazi Jewish, Arab, Armenian, Italian, and Turkish populations with carrier frequencies as high as 1:3-1:5

Question 18

What is the gene mutation and mode of inheritance in FMF?

Answer 18

Monogenic autoinflammatory syndrome due to autosomal recessive, gain-of-function mutation with gene-dosage effect in MEFV on chromosome 16p13.3

Question 19

What is the pathogenesis of FMF with regards to pyrin?

Answer 19

FMF mutations in pyrin reduce the affinity of 14-3-3 proteins for pyrin, thereby lowering the threshold for pyrin inflammasome activation

Question 20

A patient presents with severe acne, sterile skin abscesses, pyoderma gangrenosum but does not have pyogenic arthritis or fever.

What is the diagnosis?
What is the associated mutation?
What is the treatment?

Answer 20

Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND)

MEFV p.Ser242 or p.Ser208

IL-1 blockade

Question 21

A 6-month-old child who grew up in quarantine during the COVID-19 pandemic presents with 5 days of rising fever, cervical LAD, oral ulcers, splenomegaly, vomiting, and knee and ankle swelling. They also have a red maculopapular, morbilliform rash that involves palms and soles but does not migrate. The fever episode occurred after the patient received their 6-month vaccines. It also happened after the 4-month vaccines. What is the diagnosis?

Answer 21

Hyper IgD syndrome, now known as Mevalonate Kinase Deficiency-mild

Presents early in childhood, often by age 6 months
Episodes last 3-7 days
Separated by 1-2 months (symptom-free intervals)
Rising fever, chills, severe headache, splenomegaly, cervical LAD, abdominal pain, nausea, vomiting
Nondestructive polyarticular (unlike FMF) arthritis of large joints
Widespread erythematous +/- painful macules or diffuse maculopapular eruptions extending to palms and soles
Can be nodular, urticarial or morbilliform
Not migratory – different from TRAPS
No predilection for lower legs – different from FMF
Oral or vaginal aphthous ulcers
HSP or erythema elevatum diutinum (benign IgA vasculitis) have been reported
Pleurisy is uncommon
Amyloidosis is rare, often associated with V377I/I268T phenotype

Question 22

A 6-month-old child who grew up in quarantine during the COVID-19 pandemic presents with 5 days of rising fever, cervical LAD, oral ulcers, splenomegaly, vomiting, and knee and ankle swelling. They also have a red maculopapular, morbilliform rash that involves palms and soles but does not migrate. The fever episode occurred after the patient received their 6-month vaccines. It also happened after the 4-month vaccines. What diagnostic evaluation can make the diagnosis?

Answer 22

Hyper IgD syndrome, now known as Mevalonate Kinase Deficiency-mild

2 mutations in MVK and/or elevated levels of mevalonic acid in the urine
Serum IgD may or may not be elevated

Question 23

What is the epidemiology of patients with Hyper IgD Syndrome?

Answer 23

Northern European, 50% Dutch

Question 24

A 5-year-old male is referred to rheumatology clinic for recurrent high-grade fever that occurs “like clockwork” monthly, lasting 3-4 days at a time. His parents can predict the episodes as they notice him becoming more fatigued with complaints of tummy ache and headache in the days prior to the fever episode. Initially, he just had fever and malaise, but more recently, he has started to have oral ulcers and throat pain. Whenever he is swabbed for flu or Strep, it is negative. His pediatrician noticed cervical LAD. He is tracking along his growth curves. What is known to abrogate the episodes?

Answer 24

Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis Syndrome (PFAPA)

Prednisolone 0.6-2 mg/kg PO at onset of fever abrogates the fever.

Periodic fever occurring every 28 days and lasting around 1-2 days (up to 5 days), usually like clockwork
Tmax 40-41C (104-105.8F)
Aphthous stomatitis (oral lesions) - shallow, non-scarring
1 study showed frequency ~70%
Pharyngitis
1 study showed frequency ~72%
Cervical lymphadenopathy
1 study showed frequency ~88%
Malaise, chills, fatigue, arthralgia, abdominal pain, headache
Healthy in between and grows normally
Generalized LAD or HSM suggest another diagnosis

Question 25

An infant presents with recurrent fever, rash, conjunctivitis that last < 24 hours and seems to flare 1-2 hour after baths (in an air-conditioned room). There is no deafness, periorbital edema, LAD, or serositis. Ice cube test is negative. What is the diagnosis?

Answer 25

Familial Cold Autoinflammatory Syndrome (FCAS)

Hoffman et al clinical diagnostic criteria
1. Recurrent, intermittent episodes of fever and rash that primarily follow natural, experimental, or both types of generalized cold exposure
2. Autosomal dominant pattern of disease inheritance
3. Age of onset <6 months old
4. Duration of most attacks <24 hours
5. Presence of conjunctivitis associated with attacks
6. Absence of deafness, periorbital edema, lymphadenopathy, and serositis
4 of 6 criteria are strongly suggestive of FCAS

Question 26

What is the gene mutation associated with FCAS? What is the pattern of disease inheritance?

Answer 26

Mutation in NLRP3

Autosomal dominant

Question 27

What is the treatment of NLRP3-related disease?

Answer 27

First line: IL-1 blockade

Canakinumab is FDA approved for FCAS and MWS
Anakinra is FDA approved for NOMID/CINCA

IL-1 blockade does not appear to have an effect on bone lesions
Colchicine is ineffective

Question 28

What is the mutation associated with FCAS, Muckle-Well syndrome, and NOMID/CINCA? What is the pattern of inheritance?

Answer 28

GOF mutation in NLRP3 (CIAS1)

AD

Question 29

A child was found to have sensorineural hearing loss. The patient has a history of recurrent fever, urticarial rash, leg/knee pain, conjunctivitis. What laboratory result would be diagnostic of the condition? What is a complication on untreated disease (aside from SNHL)?

Answer 29

Muckle-Wells syndrome
Genetic testing for GOF mutation in NLRP3
Amyloidosis resulting in renal dysfunction

Question 30

A 6-month-old male presents with recurrent episodes of fever, urticarial rash, irritability with poor appetite, vomiting,
and decreased ROM in his knees. He has been admitted for evaluation of fever, and there is concern for meningitis, but CSF culture is always negative. What is a possible complication of this condition?

Answer 30

Neonatal Onset Multisystem Inflammatory Syndrome (NOMID)

Complications include:
Blindness from eye inflammation
High-frequency hearing loss due to chronic cochlear inflammation
Spastic diplegia and epilepsy
Progressive cognitive impairment due to increased ICP resulting in macrocephaly, frontal bossing, saddle nose

Question 31

A 15-year-old male presents with recurrent E. coli abscesses of his buttocks with fever that occurs ~21 days. Fever lasts 3-5 days. Labs remarkable for ANC < 200 and elevated ESR and CRP. ANC in between episodes is 1800.

What is the diagnosis? What is the genetic mutation associated with this condition? What is the treatment?

Answer 31

Cyclic neutropenia
Mutation in ELANE
G-CSF

Question 32

A 13-year-old boy presents with recurrent episodes of arthritis with a large, ulcerative patch of his leg that is culture negative. he recently has also developed cystic acne. XR of affected joints show erosions. Joint fluid appears inflammatory but culture negative.

What is the diagnosis? What is the genetic mutation associated with this condition? What is the treatment?

Answer 32

PSTPIP1-associated Arthritis, Pyoderma Gagrenosum, and Acne Syndrome (PAPA)

AD mutation in PSTPIP1

Arthritis may respond to corticosteroid therapy
Reports of successful treatments with anakinra, etanercept, infliximab, and adalimumab
Anecdotal evidence that IL-1 inhibition may be more beneficial for joint manifestations and TNF inhibition for pyoderma gangrenosum

Question 33

An infant presents with osteomyelitis, pustulosis, vasculitis, and severe inflammatory response syndrome. CXR reveals widening of multiple ribs with osteolytic lesion with sclerotic rim of tibia.

What treatment should be started? What is the genetic mutation associated with this condition?

Answer 33

Deficiency of IL-1R Antagonist

Tx: IL-1 blockade with anakinra, rilonacept > canakinumab

AR LOF mutation in IL1RN

Question 34

A 8-year-old female presents with recurrent fever, malaise, and generalized pustular psoriasis.

What is the diagnosis? What is the genetic mutation associated with this condition? What treatments are effective?

Answer 34

Deficiency of IL-36R Antagonist (DITRA)

Caused by biallelic loss-of-function mutations in IL36RN gene

Anakinra is relatively ineffective
TNF inhibitors, IL-12/23 and IL-17 have been reported to be effective in small case series

Question 35

A 12-year-old female presents with recurrent fever, violaceous annular plaques on trunk and extremities, “heliotrope rash”, joint pain, progressive lipodystrophy, myositis, drumstick widening of distal fingers, HSM, LAD.

What is the diagnosis? What is the genetic mutation associated with this condition? What is the first-line treatment?

Answer 35

CANDLE - chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature

Biallelic mutations in the PSMB8 gene -> impaired immunoproteasome function and accumulation of polyubiquitinated proteins in immune cells -> overactivation of many proinflammatory intracellular pathways

Tx:
Most clinical symptoms respond to high-dose steroids (1-2 mg/kg/day) but symptoms may rebound with tapering
Lipodystrophy tends to progress despite immunosuppressive and cytokine-targeted therapy
Recent therapy with JAK inhibitors appears promising (as described by Dr. Pooja Patel)

Question 36

A 3-year-old female presents with cold-sensitive, painful erythematous ulcerations of her ears, cheeks, and nose with associated low-grade fever and LAD. CXR with bilateral hazy opacities worse on the periphery.

What is the diagnosis? What is the genetic mutation associated with this condition? What is the first-line treatment?

Answer 36

STING-Associated Vasculopathy with Onset in Infancy (SAVI)

Autosomal dominant gain-of-function mutations in TMEM173 gene

Clinical manifestations and inflammatory and IFN biomarkers may improve with Jak1/2 inhibition (which blocks IFN signaling)
Respond poorly to biological agents that target proinflammatory cytokines (TNF, IL-1 and IL-6) or conventional DMARDs

Question 37

A 14-year-old female presents with recurrent oral ulcers, vaginal ulcers, and arthritis. Her oral ulcers leave behind scars and episodes are associated with recurrent fever, elevated ESR and CRP, and positive auto antibodies. She responds to colchicine treatment but has break through symptoms.

What is the diagnosis? What is the genetic mutation associated with the condition? What are the treatment options?

Answer 37

Haploinsufficiency of A20

De novo or autosomal dominant mutations in the gene TNFAIP3

Tx:
No standard treatment
Colchicine may be helpful in treating ulcers
Anti-TNF and IL-1 agents or JAK inhibitors have been effective in suppressing systemic inflammation
Hematopoietic stem cell transplant might be considered with severe or treatment-refractory disease

Question 38

A young child presents with weakness of arm, leg with numbness, difficulty walking, and difficulty speaking. His father reports that he is “always sick” with recurrent fever and skin nodules of unknown etiology. He has livedo reticularis-like rash, HSM on exam.

What is the next best diagnostic study to order? What must be considered on the differential diagnosis?

Answer 38

CT head to evaluate for lacunar stroke

Deficiency of Adenosine Deaminase 2 caused by autosomal recessive disorder caused by loss-of-function mutations in ADA2

Question 39

What other inflammatory processes are associated with or overlap with CNO?

Answer 39

pustulosis palmoplantaris
psoriasis vulgaris
severe acne
generalized pustulosis
Sweet syndrome
spondyloarthropathy
IBD

Question 40

A 9 yo F presents with pain in her distal thigh, worse at night. It started slowly but has gotten worse over the last 2 months. Now there is mild tenderness, swelling, warmth, and a purplish bump at the site of pain. She has a low grade fever. The ESR and CRP are modestly elevated. What studies may confirm the diagnosis?

Answer 40

Chronic Nonbacterial Osteomyelitis (CNO)

May have abnormal findings on XR or MRI

Question 41

What are the most common sites of CNO?

Answer 41

Metaphyseal regions of the long bones
Clavicle (medial one third of bone)
Vertebral bodies
Pelvis

Question 42

What is the relationship between arthritis and CNO?

Answer 42

Arthritis has been reported in up to 40% of CNO/CRMO patients and can be adjacent to (60%) or distant from (40%) bone lesions.

Question 43

What is the recommended imaging plan for the work-up of possible CNO?

Answer 43

1. X-rays of symptomatic regions
2. MRI (T1 native and gadolinium-enhanced plus T2 sequences) of symptomatic regions then
3. Whole-body TIRM/STIR MRI to detect asymptomatic lesions

Question 44

What is the first line treatment of CNO?

Answer 44

NSAIDs. Prostaglandins are involved in osteoclast activation, and inflammasome activation is involved in the pro-inflammatory phenotype of CNO.

NSAIDs alone are likely not sufficient to control arthritis and/or spinal involvement.

There may be flares in disease in 50% of patients after 2 years

Question 45

When would you obtain a bone biopsy in the evaluation of possible CNO?

When would you not need to obtain a bone biopsy in the evaluation of possible CNO?

Answer 45

To rule out malignancy or infection

You may not need to get bone biopsy if there are classic radiographic findings of CNO/CRMO (particularly if the clavicle is one of the bones involved)
and has a co-morbid condition such as Crohn disease or psoriasis.

Question 46

What are the treatment options for CNO that does not go into remission with NSAIDs?

Answer 46

1. Classical DMARDs: methotrexate or sulfasalazine
2. TNFi (Humira, Enbrel, Remicade) +/- MTX
3. Bisphosphonates (Pamidronate vs zoledronic acid)

Question 47

What is a mimic of CNO that presents in patients under the age of 2?

Answer 47

DIRA

Question 48

What’s the differential diagnosis for CNO?

Answer 48

Autoinflammatory disease with CNO/CRMO, including DIRA
Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA)
Majeed syndrome
Malignancy
Infection

Question 49

What’s the differential diagnosis for CNO?

12 items

Answer 49

Autoinflammatory disease with CNO/CRMO, including DIRA
Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA)
Majeed syndrome
Malignancy (e.g. primary intraosseous lymphoma, osteosarcoma, Ewing sarcoma, leukemia, and neuroblastoma)
Infection
Benign bone lesions, including osteoid osteoma and osteoblastoma
Langerhans cell histiocytosis
Rosai-Dorfman disease
Psoriatic arthritis or spondyloarthropathy
Hypophosphatasia
Immune deficiency
Hypovitaminosis C (scurvy)

Question 50

What is the classic triad of Blau syndrome/early onset sarcoidosis?

Answer 50

Rash followed within months by symmetrical poly arthritis then uveitis in the 2nd year

Polyarthritis - boggy, involving wrists/knees/ankles/PIPs, develop camptodactyly (flexion contracture)

Uveitis - insidious granulomatous iridocyclitis and posterior uveitis that can progress to panuveitis

Rash - variable

Question 51

How can an infant present with sarcoidosis without NOD2 mutation?

Answer 51

Infantile-onset panniculitis with uveitis and systemic granulomatosis

Question 52

What are the symptoms of Lofgren syndrome?

Answer 52

Acute ankle arthritis
Erythema nodosum
Hilar adenopathy

Question 53

What are the symptoms of Mikulicz syndrome?

Answer 53

Parotid and lacrimal gland enlargement with granulomatous inflammation on lacrimal gland biopsy who later develop interstitial pneumonitis

Question 54

What are clinical features of pediatric-onset “adult-type” sarcoidosis?

Answer 54

No NOD2 mutation. Less arthritis. More interstitial lung disease, hilar lymphadenopathy.

Systemic features: fever, malaise, weight loss (60-98%)
Lung: 90-100%
Hilar adenopathy: 40-67%
Peripheral adenopathy: 71-76%
Hepatosplenomegaly: 43%; mildly elevated LFTs common; liver biopsy – granulomas and cholestatic, necroinflammatory and vascular changes
Sarcoid hepatitis (severe) rarely occurs
Cutaneous: EN, erythematous macules, papules, plaques (25-42%)
Eye (uveitis most common, 25%) involvement (23-51%)
Neurological involvement 23%

Question 55

What is the most common clinical feature of neurosarcoidosis in prepubescent patients?

Answer 55

Seizure

Question 56

What is the classic histopathology of sarcoidosis?

Answer 56

Noncaseating epithelioid granulomas consist of central clusters of monocytes and macrophages in various stages of activation, epithelioid cells aligned like epithelial cells, and multinucleated giant cells

Question 57

What lab abnormalities are classically associated with pediatric sarcoidosis?

Answer 57

ACE - normal or elevated
Hypercalcemia, hypercalciuria
Genetic testing: NOD2 mutation

Question 58

What are some medications used to treat Blau syndrome/early onset sarcoidosis?

Answer 58

Steroid
Methotrexate
Anti-TNF monoclonal antibody agents

Question 59

Can the arthritis of Blau syndrome cause joint damage?

Answer 59

Yes

Arthritis seems nondestructive initially but can lead to flexion deformities, camptodactyly, and erosions

Question 60

What is the differential diagnosis for pediatric sarcoidosis?

Answer 60

Chronic infections (mycobacteria, fungi)
Primary immunodeficiency disorders (PID) with granulomatous inflammation (CGD)
Crohn’s Disease
Necrotizing granulomatous disorders (GPA, eGPA, lymphomatoid granulomatosis)
Arthritis and Uveitis - JIA
Cutaneous manifestations - atopic dermatitis, ichthyosis vulgaris
Fever and visceral involvement - sJIA

Question 61

What is the classic triad of Majeed syndrome?

Answer 61

early-onset CRMO

congenital dyserythropoietic anemia

neutrophilic dermatosis (consistent with Sweet syndrome)

Question 62

What mutation causes Majeed syndrome?

Answer 62

LPIN2

Question 63

What mutation causes DIRA?

Answer 63

IL1RN

Question 64

What mutation causes Pyogenic sterile Arthritis Pyoderma gangrenosum and Acne (PAPA) syndrome?

Answer 64

PSTPIP1

Question 65

A 3-year-old patient presents with symmetrical, progressive, nontender bony enlargement of the jaw without associated systemic symptoms and an upward gaze. What is the diagnosis?

Answer 65

Cherubism

Gene mutation in SH3-binding protein-2 (SH3BP2)
Gene mutation in PTPN11 can also result in a cherubism phenotype

Question 66

What diseases have mutation in CIAS1?

Answer 66

Mutations in CIASl are seen in a spectrum of diseases including familial cold-induced autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disorder.

Question 67

What disease should you think about if you see “storiform fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltrate” on a biopsy report?

Answer 67

IgG4-related disease

Diagnosis of IgG4-related disease is based on tissue findings of storiform fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltrate. While elevation in the serum IgG4 level is seen in IgG4-related disease, it is not sufficient for diagnosis.

Question 68

What disease has mutations in CECR1?

Answer 68

DADA-2 syndrome

deficiency in adenosine deaminase 2 syndrome, which is an autosomal recessive autoinflammatory disorder characterized by early onset fevers, strokes, and vasculopathy with livedoid rash.

Question 69

What disease has mutations in Mutations in IDUA (α-L-iduronidase)

Answer 69

mucopolysaccharidosis type I syndromes (Hurler, Hurler-Scheie, and Scheie).

Mutations in IDUA (α-L-iduronidase) are associated with mucopolysaccharidosis type I syndromes (Hurler, Hurler-Scheie, and Scheie). Patients may have early developmental delay, hepatosplenomegaly, contractures, coarse facial features, and corneal clouding.

Question 70

What auto inflammatory mutation/disease is described here:

biallelic mutation that results in reduced cellular sequestration of an inflammasome component

Answer 70

FMF/ MEFV gene

Mutations in MEFV result in less endogenous phosphorylation and sequestration, so there is a more brisk response to otherwise insignificant triggers.

Familial Mediterranean fever is usually considered an autosomal recessive disease and individuals with symptoms have 2 mutations of the MEFV gene (chromosome 16).

The M694V mutation seems to have the most severe phenotype

MEFV codes for pyrin, a protein produced by cells of the innate immune system (neutrophils, macrophages, eosinophils), serve as a primary defense against microbial products of infection. Pyrin is produced in the active form at a steady state in these cells; this protein is balanced by a series of guanosine triphosphatases (GTPases) that serve to phosphorylate the pyrin. Once phosphorylated, it can be sequestered in the cell by endogenous peptides, which renders it inactive. When bacterial virulence factors are produced, the GTPase activity decreases, which allows for the accumulation of unphosphorylated, active pyrin. These proteins serve as a trigger to assemble the pyrin inflammasome, which generates IL-1 and subsequent symptoms of inflammation. Mutations in MEFV result in less endogenous phosphorylation and sequestration, so there is a more brisk response to otherwise insignificant triggers.

Question 71

What auto inflammatory mutation/disease is described here:

mutation that results in abnormal signalling receptor accumulation on the cell surface of macrophages

Answer 71

TRAPS/ TNFRSA1

TNFRSA1 is located on chromosome 12, and mutations are inherited in an autosomal dominant fashion and cause tumor necrosis factor receptor–associated periodic syndrome (TRAPS).

Question 72

What auto inflammatory mutation/disease is described here:

mutation that results in an enzyme deficiency in the cholesterol biosynthesis pathway

Answer 72

hyper-IgD syndrome (HIDS)/ MVK

MVK is also located on chromosome 12 and codes for mevalonate kinase, which is associated with hyper-IgD syndrome (HIDS) and is inherited in an autosomal recessive pattern.

Question 73

What auto inflammatory mutation/disease is described here:

mutation that results in constitutive activation of the NLRP3 inflammasome

Answer 73

CAPS/NLRP3

NLRP3 is located on chromosome 1 and mutations are inherited in an autosomal dominant pattern and result in cryopyrin-associated periodic fever syndromes inflammatory disease (CAPS).