Case3b: Female, 9 d at initiation of follow up, East Indian ancestry, sibling of Case 3a (Family 1)

HPOsFreeText: NBS C4-acylcarnitine 2.1 umol/L, Plasma C4-acylcarnitine 2.47 umol/L, urine C4-acylcarnitine 21.66 mmol/mol creatinine, Urine C4/C3 ratio 42

NotHPOsFreeText: normal urine isobutyrylgycine ug/mg creatinine

CaseAddInfo: unremarkable clinical condition

Case3b (Level 2)

CasePreviousTesting: same as group

CaseMethod1: same as group

CaseMethod2: same as group

CaseGenotypingMethod: same as group

Variant: NM_014384.2(ACAD8):c.867C>A (p.His289Gln)

ClinVar: 5358

CAID: CA117441

gnomAD: not in gnomAD

CaseAddInfo: homozygous mutations, no data for SCAD gene variants

Case8: Male, 6 wks at initiation of follow up, European ancestry

HPOsFreeText: NBS C4-acylcarnitine 1.8 umol/L, plasma C4 acylcarnitine 1.52 umol/L, in vitro probe isoC4-acylcarnitine 0.187 umol/ g protein, in vitro probe C4-acylcarnitine 0.573 umol/g protein, elevated urine C4-acylcarnitine 25.09 mmol/mol creatinine, Urine C4/C3 ratio 88

NotHPOsFreeText: normal urine isobutyryglycine

CaseAddInfo: unremarkable clinical condition

Case8 (Level 2)

CasePreviousTesting: same as group

CaseMethod1: same as group

CaseMethod2: same as group

CaseGenotypingMethod: same as group

Variant1: NM_014384.2(ACAD8):c.512C>G (p.Ser171Cys)

ClinVar: 95589

CAID: CA223125

gnomAD: 0.02252 (European non-Finnish)

Variant2: NM_014384.2(ACAD8):c.455T>C (p.Met152Thr)

ClinVar: 5355

CAID: CA117433

gnomAD: 0.0001395 (European Non-Finnish)

CaseAddInfo: compound heterozygote specified allele 1 and 2, but not maternal and paternal. Potential splice-site alteration at exon 3(+3A>G). ACADS (SCAD-deficient) gene variants 625G>A/625G>A.

Case3: Female, 1y 5m, Chinese

HPOsFreeText: (at 21 days) 1.96 C4, 0.17 C4/C2, 2.09 C4/C3

NotHPOsFreeText: normal urine isobutyrylglycine

Case3 (Level 2):

CasePreviousTesting: same as group

CaseMethod1: same as group

CaseMethod2: same as group

CaseGenotypingMethod: same as group

Variant: NM_014384.2:c.286G>A (p.Gly96Ser)

ClinVar: n/a

CAID: CA6372895

gnomAD: 0.001453 (East Asian)

CaseAddInfo:

Case6: Male, 8y 11m, Chinese, part of Family 1

CasePresentingHPOs: HP:0000750, HP:0001328 (speech delay, learning disability)

HPOsFreeText: (at 8y 8m) 1.07 C4 umol/L, 0.13 C4/C2, 1.20 C4/C3

Case6 (Level 2):

CasePreviousTesting: same as group

CaseMethod1: same as group

CaseMethod2: same as group

CaseGenotypingMethod: same as group

Variant1: NM_014384.2:c.286G>A (p.Gly96Ser)

ClinVar: n/a

CAID: CA6372895

gnomAD: 0.001453 (East Asian)

Variant2: NM_014384.2:c.1092+1G>A

ClinVar: n/a

CAID: CA6373205

gnomAD: 0.00005790 (Latino)

CaseAddInfo: older brother of patient 5. Had not undergone expanded NBS at birth but presented with symptoms by age 8 and was diagnosed later since his younger sister has IBDHD. Trans heterozygous, inherited one allele from each parent