====== CNS degenerative disorders of childhood ======

|**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|5–10 y|Impaired intellect|Cortical blindness Deafness|Ataxia|Occasionally|Hyperpigmentation and adrenocortical insufficiency ACTH elevated|Variable course, many mildly involved. Severe variant with death in 2–5 y.|
| ::: |Acyl-CoA synthetase|May also present as newborn, adolescent, or adult|Behavioral problems||Spasticity| |Very-long-chain fatty acids in plasma| |
| ::: | | | | |Motor deficits| | | |
| ::: | | | | |Adults: Adrenomyeloneuropathy| | | |
|Neuronal ceroid lipofuscinosis (NCL; cerebromacular degeneration); infantile NCL (INCL); late infantile (LINCL); juvenile NCL (JNCL; Batten disease)|AR|INCL: 6–24 mo|Ataxia|Pigmentary degeneration of macula|Ataxia|Myoclonus|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|
| ::: |Multiple gene mutations|LINCL: 2–4 y|Visual difficulties|Optic atrophy|Spasticity progressing to decerebrate rigidity|Generalized| |Death in 3–8 y|
| ::: | |JNCL: 4–8 y|Arrested intellectual development|||Refractory| | |
| ::: | | |Seizures| | | | | |
|Subacute sclerosing panencephalitis (Dawson disease)|None: measles infection. Also reported as result of rubella.|3–22 y|Impaired intellect|Chorioretinitis|Ataxia|Myoclonic|CSF protein normal to moderately elevated. High CSF IgG((CSF γ-globulin (IgG) is considered elevated in children when IgG is > 9% of total protein (possibly even > 8.3%); definitively elevated when > 14%.)), oligoclonal bands. Elevated CSF and serum measles antibody titers. Characteristic EEG.|Variable: death in months to years|
| ::: | | |Emotional lability|Optic atrophy|Dysarthria|Akinetic| |Remissions occasional|
| ::: | | |Incoordination||Involuntary movements|Focal and generalized||Treatment: INF-α|
| ::: | | | | |Spasticity progressing to decerebrate rigidity|| | |
|Megalencephalic leukodystrophy with subcortical cysts (MLC)|MLC1 gene defect chr 22q|Infancy|Acquired macrocephaly||Ataxia|Varied|Characteristic MRI dysmyelination|Slowly progressive to adulthood; wheelchair bound by teens|
| ::: | | | | |Spasticity| | | |
| ::: | | | | |Dystonia| | | |
|Vanishing white matter/childhood ataxia with CNS hypomyelination|AR|Infancy-fatal Variants: slower|Episodic deterioration with fever, head trauma, and fear.||Ataxia|Varied|MRI: dramatic disappearance of white matter.|Infantile: fatal|
| ::: |Chr 3q27| | | |Spasticity| | |Variants are slowly progressive|
| ::: | | | | | | | |Adult variant (autosomal dominant) with ovarian dysgenesis|
|Alexander disease|AD|Infancy|Macrocephaly||Ataxia| |Demyelination; rosenthal fibers characteristic of biopsy.|Fatal infantile. Juvenile: bulbar signs, less retardation|
| ::: |GFAP gene|| | |Spasticity| | | |
|Cerebrotendinous xanthomatosis|AR|Late childhood to adolescence|Xanthomas|Cataracts|Cerebellar defects|Myoclonus|Xanthomas in lungs and tendons|Slowly progressive into middle life. Replace deficient bile acid|
| ::: |Abnormal accumulation of cholesterol||Mental deterioration|Xanthelasma|Bulbar paralysis| | | |
|Huntington disease|AD|10% childhood onset|Hypokinetic|Ophthalmoplegia|Rigidity|50% motor seizures|CT scan: "butterfly" atrophy of caudate and putamen|Moderately rapid with death|
| ::: |CAG repeat||Dystonia| |Chorea frequently absent in children|| | |
| ::: | | |Rigidity| | | | | |
| ::: | | |Dementia| | | | | |
|Refsum disease (peroxisomal disease)|AR|5–10 y|Ataxia|Retinitis pigmentosa|Ataxia|None|Phytanic acid elevated|Treat with low phytanic acid diet|
| ::: |Phytanic acid oxidase deficiency||Ichthyosis|Nystagmus|Neuropathy| |Slow nerve conduction velocity| |
| ::: | | |Cardiomyopathy||Areflexia| |Elevated CSF protein| |

{{tag>neurolists}}

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