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| Disease | Enzyme Defect and Genetics | Onset | Early Manifestations | Vision and Hearing | Motor System | Seizures | Laboratory and Tissue Studies | Course |
|---|---|---|---|---|---|---|---|---|
| Adrenoleukodystrophy and variants (peroxisomal disease) |
X-linked Xq28 Neonatal form: AR Acyl-CoA synthetase |
5–10 y May also present as newborn, adolescent, or adult |
Impaired intellect Behavioral problems |
Cortical blindness Deafness |
Ataxia Spasticity Motor deficits Adults: Adrenomyeloneuropathy |
Occasionally |
Hyperpigmentation and adrenocortical insufficiency ACTH elevated Very-long-chain fatty acids in plasma |
Variable course, many mildly involved. Severe variant with death in 2–5 y. |
| Neuronal ceroid lipofuscinosis (NCL; cerebromacular degeneration); infantile NCL (INCL); late infantile (LINCL); juvenile NCL (JNCL; Batten disease) |
AR Multiple gene mutations |
INCL: 6–24 mo LINCL: 2–4 y JNCL: 4–8 y |
Ataxia Visual difficulties Arrested intellectual development Seizures |
Pigmentary degeneration of macula Optic atrophy |
Ataxia Spasticity progressing to decerebrate rigidity |
Myoclonus Generalized Refractory |
Vacuolated lymphocytes. Biopsy, EM of skin, conjunctiva; WBC: "curvilinear bodies, fingerprint profiles." Molecular testing of CLN1, CLN2, CLN3 genes. Protein gene product testing for CLN1 and CLN2. |
Moderately slow Death in 3–8 y |
| Subacute sclerosing panencephalitis (Dawson disease) | None: measles infection. Also reported as result of rubella. | 3–22 y |
Impaired intellect Emotional lability Incoordination |
Chorioretinitis Optic atrophy |
Ataxia Dysarthria Involuntary movements Spasticity progressing to decerebrate rigidity |
Myoclonic Akinetic Focal and generalized |
CSF protein normal to moderately elevated. High CSF IgG,b oligoclonal bands. Elevated CSF and serum measles antibody titers. Characteristic EEG. |
Variable: death in months to years Remissions occasional Treatment: INF-α |
| Megalencephalic leukodystrophy with subcortical cysts (MLC) | MLC1 gene defect chr 22q | Infancy | Acquired macrocephaly |
Ataxia Spasticity Dystonia |
Varied | Characteristic MRI dysmyelination | Slowly progressive to adulthood; wheelchair bound by teens | |
| Vanishing white matter/childhood ataxia with CNS hypomyelination |
AR Chr 3q27 |
Infancy-fatal Variants: slower | Episodic deterioration with fever, head trauma, and fear. |
Ataxia Spasticity |
Varied | MRI: dramatic disappearance of white matter. |
Infantile: fatal Variants are slowly progressive Adult variant (autosomal dominant) with ovarian dysgenesis |
|
| Alexander disease |
AD GFAP gene |
Infancy | Macrocephaly |
Ataxia Spasticity |
Demyelination; rosenthal fibers characteristic of biopsy. | Fatal infantile. Juvenile: bulbar signs, less retardation | ||
| Cerebrotendinous xanthomatosis |
AR Abnormal accumulation of cholesterol |
Late childhood to adolescence |
Xanthomas Mental deterioration |
Cataracts Xanthelasma |
Cerebellar defects Bulbar paralysis |
Myoclonus | Xanthomas in lungs and tendons | Slowly progressive into middle life. Replace deficient bile acid |
| Huntington disease |
AD CAG repeat |
10% childhood onset |
Hypokinetic Dystonia Rigidity Dementia |
Ophthalmoplegia |
Rigidity Chorea frequently absent in children |
50% motor seizures | CT scan: "butterfly" atrophy of caudate and putamen | Moderately rapid with death |
| Refsum disease (peroxisomal disease) |
AR Phytanic acid oxidase deficiency |
5–10 y |
Ataxia Ichthyosis Cardiomyopathy |
Retinitis pigmentosa Nystagmus |
Ataxia Neuropathy Areflexia |
None |
Phytanic acid elevated Slow nerve conduction velocity Elevated CSF protein |
Treat with low phytanic acid diet |
ACTH, adrenocorticotropic hormone; AD, autosomal dominant; AR, autosomal recessive; CHR, chromosome; CLN, ceroid lipofuscinosis; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalogram; EM, electron microscopy; ERG, electroretinogram; IFN-α, interferon-α; MRI, magnetic resonance imaging; VER, visual evoked response; WBC, white blood cell.
bCSF γ-globulin (IgG) is considered elevated in children when IgG is > 9% of total protein (possibly even > 8.3%); definitively elevated when > 14%.
