Table 1.
Demographic, clinical and histopathological characteristics of patients with TRAK1-related encephalopathy
| Patient | 1 (A-IV.3) | 2 (A-IV.10) | 3 (B-V.4) | 4 (B-V.5) | 5 (C-IV.3) | 6 (C-IV.4) |
|---|---|---|---|---|---|---|
| Gender | M | F | M | M | F | F |
| Consanguinity | Yes | Yes | Yes | Yes | Yes | Yes |
| Age of onset (months) | 19 | 14 | 2.5 | 13 | 1.5 | 1 |
| Presenting symptoms | Perioral myoclonus followed by myoclonic hand jerks. | Perioral myoclonus followed by myoclonic unilateral upper limb coarse myoclonus. | Multifocal and generalized myoclonus. | Facial myoclonus followed by bilateral independent upper limb myoclonus. | Exaggerated startle response and recurrent episodes of generalized myoclonic jerks. | Mild myoclonic jerks evolving into episodes of prolonged generalized myoclonus. |
| Developmental delay until rapid regression | + | + | ++ | + | + | Normal |
| Neurological signs | Alert, hypotonia evolving to spasticity, constant perioral and upper limb myoclonus. | Alert, truncal hypotonia and limb spasticity, swallowing difficulties. | Spastic, continuous multifocal myoclonus. | Alert, progressive spasticity, multifocal myoclonus swallowing difficulties. | Multifocal myoclonus, progressive spasticity, poor communication skills. | Alert, multifocal myoclonus, progressive spasticity. |
| Course | Multifocal myoclonus evolved into GTC seizures with recurrent intractable SE resistant to all AEDs, steroids, IVIg. Loss of all developmental milestones at 2 years. | At 17 m episodes of recurrent GTC SE with rapid deterioration and loss of all milestones requiring tube feeding and few weeks later assisted ventilation. | Generalized and partial tonic-clonic seizures from 12 m of age, myoclonic status epilepticus at 22 m of age followed by multifocal EPC. At 3 years intractable SE and loss of all developmental milestones. | At 14 m myoclonic status followed by rapid deterioration and loss of all developmental milestones. | CPR at 4 months after unclear apneic episode. From 7 m recurrent GTCs and episodes of SE. At 28 m rapid deterioration following GTC SE. | At 7 months onset of GTC seizures and episodes of myoclonic status and GTC status. Rapid regression at 20 m after generalized SE. |
| Brain MRI | Numerous bilateral subcortical white matter foci. Second MRI showed generalized atrophy. | Generalized atrophy. | Mild frontal atrophy. | N/A | N/A | Considered normal. |
| Brain biopsy | Mild perivascular lymphocytic infiltrates, fibrillary gliosis, and activation of microglia. EM: inclusion body in a neuronal process. | Increased astrocytosis, activation of microglia, perivascular cuffing by lymphocytes. | N/A | N/A | N/A | N/A |
| Additional laboratory investigation | Blood: elevated CRP, positive CMV shell vial assay. Normal metabolic screen (blood lactate, pyruvate, ammonia, liver enzymes and amino acids profile, urine organic acids profiles). CSF PCR was negative for an array of viruses including CMV. | Blood: positive CMV shell vial assay. Normal metabolic screen. CSF: Negative PCR for viruses. | Blood: Normal metabolic screen (serum lactate, ammonia and blood amino acids and urine organic acids). | Blood: Normal metabolic screen (serum lactate, ammonia and blood amino acids and urine organic acids). | Blood: Normal metabolic screen (plasma, urine and CSF amino acid profiles; urine organic acids profile, sulphite levels, creatinine and guandinoacetate). CSF lactate levels and skin biopsy for NCL were normal. | |
| Age of death (months) | 30 | 18 | 40 | 17 | 60 | Alive |
AED = anti-epileptic drugs; CMV = cytomegalovirus; CRP = C-reactive protein; EM = electron microscopy; EPC = epilepsia partialis continua; GTC = generalized tonic-clonic seizure; IVIg = intravenous immunoglobulins; NCL = neuronal ceroid lipofuscinosis; SE = status epilepticus; N/A = not available or not relevant.