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 IgG¹⁾, 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
Alexander disease	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
Cerebrotendinous xanthomatosis	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