Table 2.
Summary of clinical, laboratory, EEG, and neuroimaging finding of metabolic epilepsy.
| IEM | Neurologic | Non-neurologic | Laboratory | EEG | Brain MRI | Brain MRS |
|---|---|---|---|---|---|---|
| Urea cycle disorders | Encephalopathy | Liver disease (sometimes) | Hyperammonemia. Respiratory alkalosis. Increased glutamine. | Slow background | Cortical and subcortical edema. BG T2-hyperintensity with thalamic sparing. Scalloped ribbon of DWI restriction at insular gray-white interface. | Prominent Glx peak |
| Organic acidemias | Encephalopathy. Choreoathetosis. | Cytopenias. Pancreatitis. Cardiomyopathy (PA). Renal disease (MMA). | Hyperammonemia. High-anion gap metabolic acidosis. Ketotic hyperglycinemia. | Slow background. Burst-suppression possible. | Diffuse swelling neonatally; delayed myelination and globi pallidi lesions later. | Decreased Glx peak (PA) |
| Disorders of biotin metabolism | Encephalopathy | Erythroderma or ichthyosis. | Hyperammonemia. High-anion gap metabolic acidosis. Lactic acidosis. Ketosis. | Burst-suppression | Intraventricular hemorrhage. Subependymal cysts. | Lactate peak |
| MSUD | Encephalopathy; opistothonus; bicycling/fencing movements. | Sweet (“maple syrup”) smell | Ketosis. Hypernatremia. Increased BCAAs and BCKAs. | Comb-like rhythm | Increased signal and cytotoxic edema myelinated structures, vasogenic edema of unmyelinated tracts | BCAA/BCKA peak (0.9 ppm) |
| Fatty acid oxidation defects | Encephalopathy (“Reye syndrome”) | Lipid storage myopathy. Liver disease. Renal cysts (GA2). | Hypoketotic hypoglycemia | Slow background | T2 hyperintensities in periventricular and subcortical WM (GA2) | Lipid peak (0.9 and 1.3 ppm) |
| Primary lactic acidosis | Encephalopathy. Infantile Parkinsonism (PC deficiency). | Dysmorphic features (PDH deficiency) | Lactic acidosis | Slow background, multifocal spikes. | T2 hyperintensities and DWI restriction of dorsal brainstem, cerebral peduncles, corticospinal tracts; subependymal cysts. | Lactate peak |
| Glycine encephalopathy | Seizures | None | High CSF glycine and CSF/plasma glycine ratio | Burst-suppression | Dysgenesis of the CC. T2 hyperintensities and DWI restriction of myelinated tracts | Glycine peak (3.55 ppm) |
| Molybdenum cofactor/sulfite oxidase deficiency | Seizures. Hyperekplexia. | None | Elevated S-sulfocysteine; low cysteine, high taurine. Increased AASA and pipecolic acid. | Burst-suppression | Diffuse swelling followed by cystic changes | S-sulfocysteine peak (3.61 ppm); taurine peak (3.24 and 3.42 ppm) |
| Disorders of GABA metabolism | Seizures. Hypersomnolence. Choreoathetosis. | Overgrowth (GABAT) | Elevated urine 4-hydroxybutyric acid (SSADH); elevated GABA, beta-alanine and homocarnosine (GABAT) | Slow background, multifocal spikes, burst-suppression. | T2 hyperintensities of globi pallidi, dentate and subthalamic nucleus (SSADH) | GABA peak (2.2–2.4 ppm; GABAT) |
| PDE | Seizures | None | Increased AASA and pipecolic acid | Slow background, multifocal spikes, burst-suppression. | Usually normal; can have dysgenetic CC | Decreased NAA peak (over time) |
| Serine biosynthesis disorders | Microcephaly. Seizures. | Ichthyosis. Ectropion, eclabion (Neu-Laxova) | Low serine in plasma and CSF | Multifocal spikes; hypsarrhythmia. | Hypomyelination | Decreased NAA peak; increased choline peak |
| Lysosomal storage disorders | Neurodegeneration. | Hydrops fetalis. Dermal melanosis. Ichthyosis (Gaucher type 2). | Decrease in specific enzyme activity. Vacuolated lymphocytes (CLN3 disease) | Fast central spikes (Tay-Sachs); vertex sharp waves (sialidosis) | Hypomyelination (GM1 and GM2 gangliosidosis, fucosidosis, Salla disease). Subdural fluid collections (NCLs). | Broad peak centered around 3.7 ppm |
| Peroxisonal disorders | Hypotonia. Seizures. | Cholestasis; renal cysts; epiphyseal stippling. Dysmorphic features. | Elevated VLCFA, phytanic acid, bile acid intermediates, pipecolic acid, low plasmalogens, | Multifocal spikes; hypsarrhythmia. | Perisylvian polymicrogyria and pachygyria; hypomyelination; subependymal cysts. | Lipid peak (0.9 and 1.3 ppm) |
| Congenital disorders of glycosylation | Hypotonia. Seizures. | Inverted nipples. Abnormal fat pads. | Elevated transaminases; coagulopathy; endocrine abnormalities | Multifocal epileptic discharges. | Pontocerebellar hypoplasia. | Decreased NAA peak |
| Disorders of copper metabolism | Seizures | Pili torti. Cutis laxa. Bladder divderticula. Metaphyseal lesions. Wormian bones. | Low serum copper and ceruloplasmin; high urine copper. | Burst-suppression | Arterial tortuosity. Subdural collections. | Decreased NAA peak |
| GLUT1 deficiency | Seizures. Abnormal eye movements. | Hemolytic anemia, pseudohyperkalemia, cataracts (specific mutations) | Low CSF glucose and lactate; low CSF/serum glucose ratio | Variable depending on type of seizure | Normal | Normal |
7DHC, 7-dehydrocholesterol; AASA, alpha-aminoadipic semialdehyde; BCAAs, branched-chain amino acids; BCKAs, branched-chain ketoacids; BGF, basal ganglia; CC, corpus callosum; DWI, diffusion weighted imaging; GA2, glutaric aciduria type 2; GABAT, GABA transaminase; Glx, glutamine/glutamate; MSUD, maple syrup urine disease; NAA, N-acetylaspartate; NCLs, neuronal ceroid lipofuscinosis; PA, propionic acidemia; PC, pyruvate carboxylase; PDE, pyridoxine-dependent epilepsy; PDH, pyruvate dehydrogenase; WM, white matter.