Table 2.
Reports of patients with ECHS1 mutations where PDC activity in various tissues was evaluated.
| Patient genotype | Elevated lactate | Elevated alanine | Urine MDHB | SCEH | PDC | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||||
| Tissue | Activity* | Mean ± SD | RR | Tissue | Activity* (%mean) | Mean ± SD | RR | Reference | ||||
| c.817A>G/c.817A>G1 | Yes | Yes | Large | FB | <9 (BLD) | 379 ± 145 | 179–616 | FB | 0.83 (50%)** | 1.66 ± 067 | 0.87–3.03 | 11 |
| FB | 1.11 (46%)** | 2.42 ± 0.88 | 1.26–4.42 | |||||||||
| Liver | 0.33 (15%)** | 2.17 ± 0.77 | 1.23–3.89 | |||||||||
| SM | 0.10 (3%)** | 3.17 ± 1.49 | 1.20–6.52 | |||||||||
|
|
||||||||||||
| c.817A>G/c.817A>G1 | Yes | Yes | Large | FB | <9 (BLD) | 379 ± 145 | 179–616 | FB | 0.88 (53%) | 1.66 ± 067 | 0.87–3.03 | |
| Liver | 0.88 (41)** | 2.17 ± 0.77 | 1.23–3.89 | |||||||||
| SM | 0.29 (9%)** | 3.17 ± 1.49 | 1.20–6.52 | |||||||||
|
|
||||||||||||
| c.433C>T/c.476A>G | Yes | Yes | Large | ND | SM | 5.8 | 5.6–9.4 | |||||
| c.673T>C/c.674G>C | Yes | NR | Large | ND | SM | 129 | 110–130 | |||||
|
| ||||||||||||
| c.197T>C/c.449A>G | Yes | NR | 229 fold | ND | FB | Normal | 10 | |||||
| c.673T>C/ c.673T>C | Yes | Yes | 39 fold | ND | SM | Normal | ||||||
| c.268G>A/c.583G>A | ND | No | 6 fold | ND | FB | Normal | ||||||
| c.161G>A/c.431dup | Yes | No | ND | ND | SM | Normal | ||||||
|
| ||||||||||||
| c.538A>G/c.583G>A | No | Yes | ND | ND | FB | Mildly reduced** | 12 | |||||
| c.538A>G/c.713C>T2 | Mildly increased | No | NR | ND | FB | Normal | ||||||
| c.538A>G/c.713C>T2 | Mildly increased | ND | NR | ND | ND | |||||||
| c.538A>G/c.476A>G | No | No | NR | ND | FB | Normal | ||||||
|
| ||||||||||||
| c.473C>T/c.414+3G>C3 | Yes | NR | 62–100 fold | FB | <9 (BLD) | 379 ± 145 | 179–616 | FB | 0.15** | 0.23–0.53 | 5 | |
| c.473C>T/c.414+3G>C3 | NR | NR | 31–39 fold | FB | <9 (BLD) | 379 ± 145 | 179–616 | FB | 0.04** | 0.23–0.53 | ||
|
| ||||||||||||
| c.88+5G>A/ c.88+5G>A4 | Yes | Yes | NR | ND | FB | 7.6 mU/CS** | 9.7–36 | 16 | ||||
| c.88+5G>A/ c.88+5G>A4 | Yes | Yes | NR | ND | FB | Normal | ||||||
|
| ||||||||||||
| c.8C>A/c.836T>C | Yes | Yes | Large | FB | <31 (BLQ) | 379 ± 145 | 179–616 | Lymph | 0.27 (17%)** | 1.63 ± 0.53 | 0.98–2.72 | This report |
| FB | 2.17 (90%) | 2.42 ± 0.88 | 1.26–4.42 | |||||||||
Corresponding numbered superscripts indicate siblings; * indicates activity reported as nmol/min/mg protein; low/reduced PDC activity are noted in bold and **.
BLD, below limit of detection; BLQ, below limit of quantitation; CS, citrate synthase; FB, fibroblasts; Lymph, lymphocytes; MDHB, 2-methyl-2,3-dihydroxybutyric acid; ND, not determined; NR, not reported; PDC, pyruvate dehydrogenase complex; RR, reference range; SCEH, short-chain enoyl-CoA hydratase; SD, standard deviation; and SM, skeletal muscle.