Table 1.
Patient 1 | Patient 2 | Patient 3 (previously reported in Loupatty et al. 2007 [12]) | Patient reported by Brown et al. 1982[11] | |
---|---|---|---|---|
Gender |
Male |
Male |
Male |
Male |
Age at presentation |
3 months |
Birth |
4 months |
Birth |
Initial presentation |
Developmental regression |
Poor feeding |
Head bobbing |
Dysmorphic features |
Age at death |
3 years |
2 years 8 months |
Alive at 8 years |
3 months |
Family history |
Distantly related British Pakistani parents |
Distantly related parents; younger sibling of Patient 1 |
Unrelated parents |
First cousin Egyptian parents |
Neonatal problems |
Vomiting |
Poor feeding |
Poor feeding |
Poor feeding |
Hypotonia |
++ |
++ |
+ |
++ |
Dystonia |
+ |
++ |
++ |
NS |
Seizures |
Myoclonus from 8 months; generalised seizures from 10 months |
Infantile spasms |
From 9 months - transient absences and episodes of eye rolling |
NS |
Developmental regression |
+ |
+ |
+ |
NS |
Episodes of acute encephalopathy |
No |
No |
+ |
NS |
Other clinical features |
Screaming episodes, sleep disturbance, central apnoea, vision impairment (optic atrophy), hearing loss, microcephaly |
Recurrent episodes of screaming, breath-holding, poor sleep, central apnoea, visual im-pairment, microcephaly |
Cerebellar ataxia - truncal ataxia, dysmetria and intention tremor |
Facial dysmorphism, tetralogy of Fallot, multiple vertebral anomalies, agenesis of cingulate gyrus and corpus callosum (PM findings) |
MRI brain |
Altered signal and atrophy in the globi pallidi, with leukoencephalo-pathy and some generalised atrophy |
Abnormal signal within the dentate nuclei and the globi pallidi, with a generalised lack of white matter (Figure 2a) |
Signal abnormalities in globi pallidi and midbrain and asymmetric involvement of cerebral peduncles (Figure 2b) |
ND |
Venous blood lactate (<2.0 mmol/L) |
1.7 |
4.0, 1.6, 1.2 |
1.7 |
NS |
CSF lactate (<2.0 mmol/L) |
3.5, 2.2 |
2.1, 2.6 |
1.3 |
NS |
Hydroxy-C4-carnitine (<0.4 µmol/L) |
ND |
0.77-1.25 |
0.45-1.73 |
ND |
Muscle respiratory chain enzyme activities (ratio to citrate synthase activity) | ||||
Complex I (0.104-0.268) |
0.068 |
0.211 |
0.089 |
ND |
Complexes II + III (0.040-0.204) |
0.010 |
0.056 |
0.096 |
ND |
Complex IV (COX) (0.014-0.034) |
0.010 |
0.016 |
0.013 |
ND |
Muscle glutathione levels |
|
|
|
|
Muscle GSH (8.5-16.7 μmol/mg) |
ND |
ND |
7.9 |
ND |
Muscle mtDNA levels determined by Southern blot analysis | ||||
Muscle mtDNA (arbitrary units relative to the multicopy nuclear 18S rRNA gene) Paediatric controls (n = 7): Mean 17.3, SD 5.3, range 12.2 - 27.8 |
ND |
ND |
29.5 |
ND |
Fibroblast enzyme activities |
|
|
|
|
PDHc (0.7-1.1 nmol/(min.mg)) |
0.3 |
0.73 |
0.62 |
ND |
COX (30–90 nmol/(min.mg)) |
25 |
ND |
117 |
ND |
HIBCH (7.9 ± 1.3 nmol/(min.mg)) |
<2.6 |
<2.6 |
<2.6 |
~20% of controls |
HIBCH mutations | Homozygous c.950G <A; p.G317E | Homozygous c.950G <A; p.G317E | Compound heterozygous c.365A <G; p.Y122C and IVS2-3C <G; p.R27fsX50 | Homozygous c.219_220insTTGAATAG; p.K73fsX86 |
Key: COX = cytochrome oxidase; GSH = glutathione; ND = not determined; NS = not stated in original report; PDHc = pyruvate dehydrogenase complex; PM = post mortem; numbers in bold are outside the reference range, indicated in the left column.