Table 1. Summaries of the case histories of the four patients.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | |
|---|---|---|---|---|
| Age at presentation (years) | 3 | 6 | 20 | 24 |
| Age at death (years) | 5.5 | Alive at 16 | 44 | Alive at 31 |
| Symptoms at presentation | Seizures | Encephalitis-type presentation | Diplopia | Seizures |
| Clinical phenotype | Alpers-Huttenlocher | MEMSA+ | SANDO | “MELAS-like” |
| Blood/CSF results | GGT 170 IU/l (reference <20 IU/L), AST 490 IU/L (reference range 5 to 45 IU/l) | ↑lactate 2.6mmol/L (<2) Liver function normal; ↑Plasma alanine 537 mcmol/L (150–450); ↓Plasma arginine 28 mcmol/L (40–120); CSF lactate 1.6mmol/L (<2); ↑CSF protein 1.32 g/L (0.15–0.6); CSF 5MTHF 29 (46–120) | ↑ lactate 2.3mmol/L (< 1.65); CK 329 | Normal lactate; Normal CSF exam |
| Neurophysiology | - | EEG: Intermittent runs of rhythmic delta activity; CS: sensory neuropathy affecting legs | NCS: Severe axonal neuropathy | NCS: Moderately severe axonal sensory motor neuropathy |
| Radiology | Chronic grey matter ischaemia | MRI: Bilateral occipital lesions around calcarine sulci | - | MRI: Right occipital infarct |
| Neuropathology | Cortical degeneration in the occipital and parietal lobes, typical of PNDC. Bilateral hippocampal sclerosis. Hepatic microsteatosis | Brain biopsy: Non-specific; Muscle histology: COX-negative fibres | Muscle histology: ↑ no. of ragged red fibres and > 10 COX-negative fibres | Muscle histology: Ragged red fibres and COX-negative fibres and marked variation in fibre size with scattered groups of atrophic fibres. |
| Muscle Respiratory Chain enzymes | - | Complex I 0.126 (0.104–0.268); Complex II 0.159 (0.040–0.204); Complex IV 0.026 (0.014–0.034) | Complex I 0.170 (0.104–0.268); Complex II 0.077 (0.040–0.204); Complex IV 0.024 (0.014–0.034) | - |
Key: 5MTHF, 5-methyltetrahydrofolate; AST, aspartate aminotransferase; COX, cytochrome oxidase; EEG, electroencephalogram; GGT, gamma-glutamyltranspeptidase; MELAS, mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes; MEMSA, myoclonic epilepsy, myopathy, sensory ataxia; NCS, nerve conduction studies; PNDC, progressive neuronal degeneration of childhood; SANDO, Sensory Ataxia Neuropathy Dysarthria Ophthalmoplegia.