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: AR5–10 yImpaired intellectCortical blindness DeafnessAtaxiaOccasionallyHyperpigmentation and adrenocortical insufficiency ACTH elevatedVariable course, many mildly involved. Severe variant with death in 2–5 y.
Acyl-CoA synthetaseMay also present as newborn, adolescent, or adultBehavioral problemsSpasticity 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)ARINCL: 6–24 moAtaxiaPigmentary degeneration of maculaAtaxiaMyoclonusVacuolated 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 mutationsLINCL: 2–4 yVisual difficultiesOptic atrophySpasticity progressing to decerebrate rigidityGeneralized Death in 3–8 y
JNCL: 4–8 yArrested intellectual developmentRefractory
Subacute sclerosing panencephalitis (Dawson disease)None: measles infection. Also reported as result of rubella.3–22 yImpaired intellectChorioretinitisAtaxiaMyoclonicCSF 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 labilityOptic atrophyDysarthriaAkinetic Remissions occasional
IncoordinationInvoluntary movementsFocal and generalizedTreatment: INF-α
Spasticity progressing to decerebrate rigidity
Megalencephalic leukodystrophy with subcortical cysts (MLC)MLC1 gene defect chr 22qInfancyAcquired macrocephalyAtaxiaVariedCharacteristic MRI dysmyelinationSlowly progressive to adulthood; wheelchair bound by teens
Vanishing white matter/childhood ataxia with CNS hypomyelinationARInfancy-fatal Variants: slowerEpisodic deterioration with fever, head trauma, and fear.AtaxiaVariedMRI: dramatic disappearance of white matter.Infantile: fatal
Chr 3q27 Spasticity Variants are slowly progressive
Adult variant (autosomal dominant) with ovarian dysgenesis
Alexander diseaseADInfancyMacrocephalyAtaxia Demyelination; rosenthal fibers characteristic of biopsy.Fatal infantile. Juvenile: bulbar signs, less retardation
GFAP gene Spasticity
Cerebrotendinous xanthomatosisARLate childhood to adolescenceXanthomasCataractsCerebellar defectsMyoclonusXanthomas in lungs and tendonsSlowly progressive into middle life. Replace deficient bile acid
Abnormal accumulation of cholesterolMental deteriorationXanthelasmaBulbar paralysis
Huntington diseaseAD10% childhood onsetHypokineticOphthalmoplegiaRigidity50% motor seizuresCT scan: “butterfly” atrophy of caudate and putamenModerately rapid with death
CAG repeatDystonia Chorea frequently absent in children
Refsum disease (peroxisomal disease)AR5–10 yAtaxiaRetinitis pigmentosaAtaxiaNonePhytanic acid elevatedTreat with low phytanic acid diet
Phytanic acid oxidase deficiencyIchthyosisNystagmusNeuropathy Slow nerve conduction velocity
CardiomyopathyAreflexia Elevated CSF protein

1 CSF γ-globulin (IgG) is considered elevated in children when IgG is > 9% of total protein (possibly even > 8.3%); definitively elevated when > 14%.
  • neurolists/cns_degenerative_disorders_of_childhood.txt
  • Last modified: 4 years ago
  • by icna