Table 1 Biochemical parameters observed in nine new cases of RRM2B deficiency
From: The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency
Patient | Highest serum lactate | Lactate: pyruvate ratio | CSF lactate | Creatine kinase | Free carnitine | Acylcarnitines | Plasma amino acids | Urinary organic acids | Complex Ia | Complex IIa | Complex IIIa | Complex II+IIIa | Complex IVa | Citrate synthaseb | mtDNAc |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
A | 7 | ND | ND | 1209 (<170) | ND | ND | Normal | Increased lactate, 4-OH-phenyllactate, 4-OH-phenylpyruvate, Krebs cycle intermediates, 3OHB | 13% | 16% | 16% | ND | 16% | 234% | ND |
B | 4.6 | 38 | 3.5 | 330 (<145) | 93 (14–53) | Global mildly increased acylcarnitines, hydroxyacyl-carnitines | Raised alanine and glycine; decreased serine, valine, cysteine | Increased lactate, 4-OH-phenyllactate, succinate, benzoate, mildly increased 3OHB, adipate, suberate | 4 (12–29) 33% | 112 (23–49) 228%b | 43 (223–454) 19% | ND | 10 (114–250) 8% | 377 (82–150) 550% | 6% |
C | 3.2 | ND | ND | 361 (<400) | 37 (13–80) | Normal | Normal | Strong lactate, moderate pyruvate, fumarate, citrate, malate, mild 2OH valerate, 3OHB, 2OHB | 0.087 (0.104–0.268) 83% | ND | ND | 0.061 (0.04–0.204) 100% | 0.005 (0.014–0.034) 35% | ND | 5% |
D | 5 | ND | ND | 91 (<240) | ND | Normal | Normal | Variably raised fumarate | 0.004 (0.104–0.268) 3.8% | ND | ND | 0.005 (0.04–0.204) 12.5% | 0.001 (0.014–0.034) 7% | ND | 20% |
E | 5.7 | ND | 5.6 | 546 (<204) | ND | Elevated C2 | Normal | Slightly increased lactate, fumarate, malate | ND | ND | ND | ND | ND | ND | ND |
F | 6.1 | ND | ND | 340 (<374) | 31.6 (21–53) | Normal | Raised alanine | Markedly increased 3OHB, moderate lactate, pyruvate, fumarate, malate, aconitate, citrate, mild 2- ethyl hydracrylate | ND | ND | ND | ND | ND | ND | 4% |
G | 8.2 | 54 | 3.3 | 220 (<400) | 35 (13–80) | Mildly raised malonyl-carnitine | Raised alanine | Grossly raised lactate, pyruvate, 2OHB, fumarate, citrate, 4OHphenyllactate, 4OHphenylpyruvate, 3OHB, 3OHISV | 0.018 (0.104–0.268) 17.3% | ND | ND | Undetectable | Undetectable | ND | 6% |
H | 7.4 | 7.4 | 4.7 | 292 (<200) | Normal | Normal | Raised alanine | Normal | 0.006 (0.068–0.14) 8.8% | 0.08 (0.098–0.192) 81.6% | 0.046 (0.209–0.899) 22% | ND | 0.031 (0.613–1.635) 5% | ND | 3% |
I | 41.7 | ND | 2 | 223 (<400) | 17 (13–80) | Normal | Raised alanine | Grossly elevated lactate, pyruvate, moderated 2OHB, mildly 2OH valerate, 2 oxoisocaproate, 3MGA, 3OH adipate, 4OH phenyllactate | 0.127 (0.104–0.268) 100% | ND | ND | 0.025 (0.04–0.204) 62.5% | 0.002 (0.014–0.034) 14% | ND | 2% |
