Table 2.

Clinical manifestations, molecular profile, treatment, and outcomes of patients with defect affecting the inflammasome (n = 21).

Center	Patient (Age of diagnosis (years)/sex)	Age of onset of symptoms (months)	Clinical features	Laboratory features	Family history (Consanguinity/Family history)	Initial diagnosis	Molecular details	Treatment details	Follow-up duration and outcomes
Hyper IgD Syndrome/Mevalonate Kinase Deficiency (MVK) (n= 8)
PGIMER	Pt. 13 (1.33 y/M)	2 months	• Fever • Jaundice • Cholestatic • hepatosplenomegaly anemia • Failure to thrive	CRP: 290 mg/L ESR: 110 mm/hr	Yes (Younger brother of patient 14)	Neonatal cholestasis with sepsis	MVK exon 9; c.803 T>C; p.Ile268Thr exon 10; c.976G>A; p.Gly326Arg Missense (phase unknown)	Thalidomide	Alive intermittent episodes of fever present
	Pt. 14 (4.5 y/M)	2 months	• Fever • Jaundice • Anemia,generalized lymphodenopathy, hepatosplenomegaly • Failure to thrive	CRP: 56 mg/L ESR: 38 mm/hr	B/o Pt 13	Sepsis	MVK exon 9; c.803 T>C; p.Ile268Thr exon 10; c.976G>A; p.Gly326Arg Missense Same as Pt. 13	Thalidomide	Alive and well
	Pt. 15 (3.5 y/F)	6 months	• Polyarthritis (wrist, elbows, knee), • abdominal pain, Diarrhea, colitis • Anemia, hepatosplenomegaly, generalized lymphadenopathy • Global developmental delay	CRP:160 mg/L ESR:109 mm/h Bone marrow biopsy: Dyserythropoiesis with lymphoid aggregates Gut biopsy: acute on chronic inflammation IgG: 2,079 mg/dL IgA: 303 mg/dL	3rd degree consanguinity, no similar illness in family	JIA/Blau/IBD arthritis	MVK exon 6; c.546G>T; p. Leu182Phe Homozygous, Missense	CS, MTX, AZA	Alive and well
SGPGI	Pt. 16 (15 y/M) Ref (14)AM	3 months	• Fever • Rash • Arthralgia • Pleuritis • Peritonitis • Hepatosplenomegaly, generalized lymphadenopathy	CRP: 80 mg/L ESR: 90 mm/hr IgG: 1,465 mg/dL IgA: 1,166 mg/dL IgM: 58.6 mg/dL IgD: 938 mg/dL	Sibling of Pt 17	AID ? HIGD syndrome	MVK Exon 11 c.1129G>A p.V3771	NSAIDs Change in treatment: DMARDs stopped	NA
	Pt. 17 (11y /M) (14)AM	2 months	• Fever • Rash • Arthralgia • Hepatosplenomegaly, generalized lymphadenopathy • Peritonitis, adhesions on laparotomy	IgG:1377mg/dL IgA:633mg/dL IgM:119.1mg/dL IgD: 1363mg/dL	Sibling of Pt 16	AID ? HIGD syndrome	MVK Exon 11 c.1129G>A p.V3771	NSAIDs Change in treatment: DMARDs stopped	NA
BJWHC	Pt. 18 (3 y/M)	12 months	Fever Petechial rash Recurrent cervical adenitis Sinusitis Hepatosplenomegaly	-	-	-	MVK exon 2; c.10G>T; p.Glu4Ter (this is novel) exon 11; c.1129G>A; p.Val377lle Het/AR (this is already known as common Dutch founder variant)	NA	Doing well
	Pt. 19 (0.91 y/M)	15 days	• Fever • Rash Failure to thrive • Dactylitis • Perianal abscess • Otomyocosis	IgG: 2,400 mg/dL IgA: 159 mg/dL IgM: 341 mg/dL CD3: 3,724 CD19: 1,375 CD56: 516 NBT: Normal (98%)	No	PID	MVK Exon11; c.1097A>G; Asp366Gly Novel and homozygous Not published	CS	NA
CMC Vellore	Pt. 20 (1y/F)	NA	Recurrent infections Fever Anemia Failure to thrive	IgG: 520mg/dL IgA: 43mg/dL IgM: 39mg/dL TG and Ferritin: increased Fibrinogen: normal Coombs: 1+ NBT: normal	NA	NA	MVK Exon7; c.644G>A; p.Arg215Gln Homozygous	NA	NA
Cryopyrin-Associated Periodic Syndromes (CAPS)/ Muckle –Wells Syndrome (MWS)/Neonatal-Onset Mutisystem Inflammatory Disease (NOMID) (n= 7)
PGIMER	Pt. 21 (10 y /F) (31)AM	1 month	• Recurrent urticarial rash • Arthritis (ankle and wrist) • hypertension, • conjunctivitis, opticatrophy, • nephrotic range anasarca, proteinuria, • hypothyroidism • CSVT	CRP: 19.5 mg/L ESR: 51 mm/hr Renal biopsy: AA Amyloidosis IgG: 623 mg/dL; IgA: 253mg/dL IgM: 282 mg/dL	No	Atypical nephrotic syndrome	NLRP3 (exon 3; c.1055C > T; p.Ala352Val) Substitution	CS, thalidomide, enalpril, amlodipine	Died due to amyloid associated renal failure
	Pt. 22 (13 y//F)	Infancy	• Fever • Rash • Arthritis with bony overgrowth • Headache, • Short Stature	CRP: 60 mg/L ESR: 98 mm/hr FNAC, abdominal fat pad, amyloidosis	-	Systemic JIA	NLRP3 exon 3; c.913G>C; p.Asp305His	CS, thalidomide	Alive
	Pt. 23 (11 y/M)	NA	• Fever • Arthritis • Amyloidosis, • renal failure	CRP: 58 mg/L ESR: 89 mm/hr FNAC, abdominal fat pad, renal biopsy, amyloidosis	-	Systemic JIA	NLRP3 exon 3; c.1792C>T; p.Thr349Ile	CS	Died due to amyloid associated renal failure
	Pt. 24 (6.5 y/M) (32)AM	18 months	• Fever • Erythematous macular non itchy rash, later painful nodular • Seizures with meningitis, • SNHL	CRP: 65 mg/L ESR: 96 mm/hr Skin panniculitis, non specific perivascular dermatitis MR brain: Bilateral Bilateral cerebellar atrophy with mild hydrocephalus	No	Tubercular meningitis	NLRP3 genetic screening negative for all exons	CS, thalidomide	Died
SGPGI	Pt. 25 (4 y/F)	Since birth	• Fever • Arthritis • Urticaria • Knee flexion contractures • Short stature • Hepatosplenomegaly	CRP:11.7 mg/L ESR: 30 mm/hr	No	Oligo JIA, NOMID	Mutation screening under process	Colchicine	Doing well
	Pt. 26 (5 y/M)	Since birth	• Fever • Arthritis • Urticaria, • Lymphadenopathy, hepatosplenomegaly	CRP:12 mg/L ESR: 90 mm/h IgG:1,590 mg/dL IgA: 275 mg/dL IgM: 109 mg/dL IgE: 409.8 mg/dL	No	NOMID	Mutation screening under process	Colchicine	Doing well
BJWHC	Pt.27 (1.33 y /M)	D1 of life	• Fever • Urticarial rash • Hepatosplenomegaly • Hypertelorism • Macrocephaly • Delay in cognitive milestones	CRP: 10 mg/L ESR: 140.5 mm/h MRI brain: Mild cerebral atrophy with dilated lateral ventricles and cisterns IgG: 1,472 mg/dL IgA: 124 mg/dL IgM: 181 mg/dL IgE: 785 mg/dL	No	AID	NLRP3 exon 4; c.2263G>A/G>C; p.Gly755Arg	CS, NSAIDs	Died
NLR Family Pyrin Domain containing 12 (NLRP12) (n= 2)
SGPGI (17)2)	Pt. 28 (4 y/F)	Since birth	• Fever • Diarrhea • Pneumonia • Arthritis	CRP: 54 mg/L ESR: 34 mm/hr	No	PID	NLRP12 exon 9; c.2935A>G; p.Ser979Gly published	CS	NA
			• Cervical lymphadenopathy and hepatosplenomegaly, • Skin pustules,subcutaneous abscess • Meningitis, SNHL	Gut biopsy: cryptitis with occasional crypt distortion NBT: Normal CD3, CD19, CD56: Normal
	Pt. 29 (1 y/M)	1 month	• Fever • Urticarial rash, bullous eruptions over fingers, pustular skin lesion • Cervical and axillary lymphadenopathy	CRP: 72 mg/L ESR: 103 mm/hr USG: synovial thickening of joint and both radiocarpal joints. C3/C4: 1.73 mg/dL /0.25 mg/dL	-	AID	NLRP12 exon3; c.779C>T; p.Thr260Met Heterozygous VUS Not published	CS	Well
Familial Mediterranean Fever (FMF) (n= 2)
BJWHC	Pt. 30 (0.91y/F)	4 months	Fever Irritability Maculopapular rash Recurrent abdominal pain Hepatomegaly	CRP: 39 mg/L ESR: 53 mm/hr CD3: 4,084 CD19: 2,106 CD56: 128 NBT: 97%	No	AID	PLCG2 exon 2;c.62C>T; p.Ala21Val het/AD/VUS het/AD/VUS MEFV exon 2; c.464G>C; p.Arg155Thr) Het/AD/VUS Not previously published. This is a non-confirmatory variant as per new Eurofever/ PRINTO classification criteria	Colchicine	Doing well
PGIMER	Pt. 31 (1.66 y/M)	9 months	Oral ulcers	CRP: 1.87 mg/L ESR: 37 mm/hr TH17/STAT3: reduced IgE: Normal NBT: Normal CD3, CD19, CD56,CD4, CD8: Normal	N/Yes (oral ulcers in father; Not Screened)	PID (TH17/PSTAT1 defects)	MEFV exon 10; c.2177T>C; p.Val726Ala heterozygous, missense. This is a non-confirmatory variant as per new Eurofever/ PRINTO classification criteria	Fluconazole Colchicine	Alive
PLCG2 associated antibody deficiency and immune dysregulation (APLAID) (n= 2)
PGIMER	Pt. 32 (9 y/F)	24 months	• Generalized Erythematous macular rash, bilateral knee and elbow arthritis, two episodes of intussception, otitis media • Pneumonia, • Recurrent vaginal bleeding • Short stature	HRCT: bilateral hyper inflated lung with fibrotic changes Skin Biopsy: non-specific perivasculitis with no immune deposits ANA: 2+ speckled and nucleolar C3/C4: 73 mg/dL/ <8mg/dL CH50: 166% (69–129) IgG: 1,683 mg/dL(540–1,610) IgA: >594mg/dL (50–240) IgM: 117 mg/dL(50–180) IgE: >10,000 IU/mL CD3: 51.8 (55–78) CD19: 40.89 (10–31) CD56: 3.11	Younger male sibling expired at 9 months, diarrhea, necrotic skin rash	SLE	PLCG2 exon 22; c.2393 A>G; pAsn798Ser heterozygous, missense	CS, thalidomide, AZA	Died
	Pt. 33 (3 y/M)	4 months	• Fever • Rash (multiple supportive lesions, erythematous plaques pustular lesions, alopecia) along with scars • Photosensitivity • Flexural contractures at small joints of hand, claw hand • Bilateral corneal epithelial defect with corneal ulcers and corneal opacity • Phimosis	CRP: 70 mg/L ESR: 100 mm/hr Skin Biopsy: Epidermis shows Epidermis shows hyperkeratosis, focal neutrophilic crust over stratum corneum, basal cell vacuolation, perivascular infiltrates ANA: Negative IgA: >595 mg/dL IgM: 89 mg/dL IgE: 8,856 mg/dL CD3/CD19/CD56: normal NBT /TH17/STAT3: normal	No	Kindler syndrome, hyper IgE syndrome	PLCG2 exon 22; c.2393 A>G; pAsn798Ser heterozygous, missense	CS, MTX, IVIg	Died

AID, Autoinflammatory disorder; ANA, Antinuclear antibodies; AZR, Azathioprine; BD, Behcet disease; BJWHC, Bai Jerbai Wadia Hospital for Children, Mumbai, India; CMC, Christian Medical College and Hospital, Vellore, India; CRP, C-reactive protein; CS, Corticosteroids; CSVT, Cerebral sinovenous thrombosis; CT, Computed tomography; CTA, Computed tomography angiography; CYC, intravenous pulse cyclophosphamide; ESR, Erythrocyte sedimentation rate; FNAC, Fine needle aspiration cytology; HCQS, Hydroxychloroquine; Ig, Immunoglobulin; JIA, Juvenile idiopathic arthritis; MRI, Magnetic resonance imaging; MTX, Methotrexate; MMF, Myocphenolate mofetil; MVL, Mevalonate kinase; NBT, Nitroblue tetrazolium; NLRP3, NLR family pyrin domain containing 3; NLRP12, NLR family pyrin domain containing 12; PID, Primary immunodeficiency disorder; PGIMER, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India; PLCG2, Phospholipase C gamma 2; Ref, Reference of previously reported paper; SGPGI, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India; SNHL, Sensory neural hearing loss; TG, Triglycerides; Y, years.