Table 1.
Pre-treatment Genetic, Clinical, Biochemical, and Histopathological Findings in Individuals with FLAD1 Variants
| ID | Sex | Consanguineous | FLAD1 Variants (GenBank:NM_025207.4) | FADS1 Variants (GenBank:NP_079483.3) | Affected Domain | Age of Onset | Status | Responsive to Riboflavin | Increased Blood Acylcarnitinesa | Elevated Organic Acidsa |
Muscle Investigations |
||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Respiratory-Chain Activitiesb | Other Mitochondrial Enzyme Activities | Histology | |||||||||||
| S1a | F | yes | c.[1484_1486delCCT]; [1484_1486delCCT] | p.[Ser495del];[Ser495del] | FADS | 32 hr | died at 3 days | NT | C5, C8, C14, C5-DC | ethylmalonic, adipic, suberic, and dehydrosebacic acids, hexanoylglycine | within control range | NR | vacuoles in muscle fibers (EM not done) |
| S1b | M | yes | c.[1484_1486delCCT]; [1484_1486delCCT] | p.[Ser495del];[Ser495del] | FADS | 3 months | alive at 22 years | yes | C4 | ethylmalonic and methylsuccinic acids | NR | NR | NR |
| S2 | F | no | c.[568_569dupGC]; [1588C>T] | p.[Val191Glnfs∗10]; [Arg530Cys] | MPTb (fs), FADS | 20 years | alive at 44 years | yes | C8, C10, C10:1 | ethylmalonic and glutaric acids, lactate | CII↓, CIII↓, CIV↓ | CS↑ | lipid-storage myopathy, faint COX staining |
| S3 | F | no | c.[836delT]; [1588C>T] | p.[Phe279Serfs∗45]; [Arg530Cys] | MPTb (fs), FADS | 44 years | alive at 56 years | yes | C5, C8, C10, C10:1, C14 | ethylmalonic acid, tiglylglycine | CI+III↓, CII+III↓ | CS↑ | lipid-storage myopathy, muscle beta oxidation (C4: 132%; C8: 15%; C16: 56%) |
| S4a | F | yes | c.[526_537delinsCA]; [526_537delinsCA] | p.[Ala176Glnfs∗8]; [Ala176Glnfs∗8] | MPTb (fs) | 4 months | alive at 8 years | yes | C4, C6, C8, C10, C14, C14:1, C14:2, C16:1, C18, C18:1, C18:2 | adipic, suberic, ethylmalonic, and methylsuccinic acids, ketosis | CI↓, CII↓ | PDH↓ | lipid-storage myopathy |
| S4b | F | yes | c.[526_537delinsCA]; [526_537delinsCA] | p.[Ala176Glnfs∗8]; [Ala176Glnfs∗8] | MPTb (fs) | 8 months | died at 16 years, 2 months | discontinued (side effects) | normal or C4-OH, C5, C6, C8, C10, C14:1, C16:1 | NR | NR | NR | NR |
| S5 | M | yes | c.[401_404delTTCT]; [401_404delTTCT] | p.[Phe134Cysfs∗8]; [Phe134Cysfs∗8] | MPTb (fs) | 6 months | died at 6 months | NT | C3, C5, C6, C8:1 | adipic acid | CI↓, CII+III↓ | CS↑ | lipid-storage myopathy, faint COX staining |
| S6 | F | no | c.[324delG]; [498delC;508T>C] | p.[Arg109Alafs∗3]; [Ser167Profs∗20; Phe170Leu] | MPTb (fs) | birth | died at 9 months | no | NR | NR | CI↓, CII+III↓ | CS↑ | lipid-storage myopathy, absent SDH staining, several NADH- and COX-negative fibers |
| S7 | F | yes | c.[401_404delTTCT]; [401_404delTTCT] | p.[Phe134Cysfs∗8]; [Phe134Cysfs∗8] | MPTb (fs) | 2 months | died at 4 months | NT | C4, C6, C8, C10, C10:1, C12, C14:1, C16, C16:1, C18:1 | ethylmalonic and glutaric acids | NR | NR | lipid-storage myopathy, faint SDH staining, normal COX |
Abbreviations are as follows: ↓, decrease; ↑, increase; C4, butyrylcarnitine; C4-OH, OH-butyrylcarnitine; C5, isovalerylcarnitine; C5-DC, glutarylcarnitine; C6, hexanoylcarnitine; C8, octanoylcarnitine; C10, decanoylcarnitine; C10:1, decenoylcarnitine; C12, dodecanoylcarnitine; C14, tetradecanoylcarnitine; C14:1, tetradecenoylcarnitine; C14:2, tetradecadienoylcarnitine; C16, hexadecanoylcarnitine; C16:1, hexadecenoylcarnitine; C18, octadecanoylcarnitine; C18:1, octadecenoylcarnitine; C18:2, octadecdienoylcarnitine; CI–CIV, complexes I–IV; COX, cytochrome c oxidase; CS, citrate synthase; EM, electron microscopy; F, female; FADS, FAD synthase domain; fs, frameshift; M, male; MPTb, molybdopterin binding domain; NR, not reported; NT, not tested; PDH, pyruvate dehydrogenase; and SDH, succinate dehydrogenase.
Actual values are reported in Table S3.
Actual values are reported in Table S5.