Table 3.
Genetic complex III defects sharing their clinical pattern
| Sign/symptom | UQCRB[12] | CYC1[13] | UQCRC2[14] | LYRM7£[18] |
|---|---|---|---|---|
|
| ||||
| Age at onset | 8 | 5/28 | NN/NN/NN | 20/6 |
|
| ||||
| Present age | 18 | 3/21 | 5/4/1.5 | 2.3*/1.2* |
|
| ||||
| Metabolic crises | +£ | +/+£ | +/+/+££ | +/+ |
| Severe acidosis | + | +/+ | +/+/+ | +/+ |
| Hyperlactatemia | + | +/+ | +/+/+ | +/+ |
| Hypoglycemia | + | ±/+ | +/+/+ | ?/+ |
| Hyperammonemia | ± | +/+ | +/+/? | +/? |
| Ketosis | + | +/+ | +/+/? | ?/? |
|
| ||||
| Liver failure | ± | 0/± | 0/0/0 | 0/0 |
|
| ||||
| Brain function | N | N | N/N/N | PR$/PR$$ |
|
| ||||
| Heart function | N | N | N | N |
|
| ||||
| Complex III | ||||
| Liver | 6% | 4%/? | ? | ?/0% |
| Skeletal Muscle | ? | 24%/45% | ? | 22%/? |
| Fibroblasts | 12% | 25%/24% | 50%/?/? | ?/26% |
0= absence of the sign; N=Normal function; Age at onset is expressed in months or as NN for neonatal period; present age is expressed in years, *=age at death; frequency of acute metabolic crises was reported as ~ four times a year from 0.5 to 4 years of age, progressively declining to less than one per year during adolescence (£) or as frequent and decreasing with age (££);severe acidosis=pH dropping to ~7.0 or below; ± liver failure= factor V<40% only observed during one acute metabolic crisis; PR=Psychomotor Regression, ($)=neurological development normal up to 20 months of age, severe psychomotor regression with loss of head control, spastic tetraparesis, marked demyelination and vacuolization of the white matter appearing after an acute metabolic decompensation with pH 6.78; ($$)=neurological development normal up to 6 months of age, severe psychomotor regression with loss of contact, profound axial hypotonia and peripheral hypertonia following a 3 day-acute metabolic crisis with coma.
During the preparation of this manuscript, 7 additional patients with LYRM7 mutations were identified based on the presence of a distinct multifocal leukoencephalopathy [19].
Metabolic crises were not reported in these patients who presented however with one or several episodes of subacute encephalopathy, during which metabolic parameters are not mentioned.