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Clinical Neurology · Child Neurology

Storage Diseases

Glycogen and lysosomal storage diseases of relevance to neurology.

Glycogen storage diseases

DiseaseEnzyme deficiencyHypoglycemiaHepatomegalyHyperlipidemiaMuscle symptomsMnemonic
von GierkeGlucose-6-phosphataseYesYesYesNone
PompeAcid maltase (lysosomal α-1,4-glucosidase)NoYesNoMuscle weakness (develops HF)P for Pump (heart)
CoriGlycogen debrancherYesYesYesMyopathy
AndersenGlycogen branching enzymeNoYesNoNone
McArdleMuscle glycogen phosphorylaseNoNoNoExercise-induced crampsM for Muscle (glycogen phos)
HersLiver glycogen phosphorylaseYesYesNoNoneH for Hepatic (glycogen phos)

Lysosomal storage diseases

DiseaseFindingsDeficient enzymeAccumulated substrateInheritance
Gaucher
  • Hepatosplenomegaly
  • Aseptic necrosis of femur
  • Bone crises
  • Gaucher cells (macrophages look like crumpled paper)
GlucocerebrosidaseGlucocerebrosideAR
Niemann-Pick
  • Progressive neurodegeneration
  • Hepatosplenomegaly
  • Cherry-red spot (on macula)
  • Foam cells
SphingomyelinaseSphingomyelinAR
Tay-Sachs
  • Progressive neurodegeneration
  • Developmental delay
  • Cherry-red spot
  • Lysosomes with onion skin
Hexosaminidase AGM2 gangliosideAR
Metachromatic leukodystrophyCentral and peripheral demyelination with ataxia, dementiaArylsulfatase ACerebroside sulfateAR
Fabry
  • Peripheral neuropathy of hands/feet
  • Angiokeratomas
  • Cardiovascular disease
α-galactosidase ACeramide trihexosideXR
Krabbe
  • Peripheral neuropathy
  • Developmental delay
  • Optic atrophy
  • Globoid cells
GalactocerebrosidaseGalactocerebrosideAR
Hurler
  • Developmental delay
  • Gargoylism
  • Airway obstruction
  • Corneal clouding
  • Hepatosplenomegaly
α-L-iduronidaseHeparan & dermatan sulfateAR
HunterMild Hurler + aggressive behavior, no corneal cloudingIduronate sulfataseHeparan & dermatan sulfateXR
Quick differentials
  • Gaucher: no neurological symptoms
  • Niemann-Pick & Tay-Sachs: both associated with a cherry-red spot; Niemann-Pick also has HSM
  • Fabry & Krabbe: both have peripheral neuropathy. Fabry has normal development and angiokeratomas; Krabbe has developmental delay and optic atrophy
  • Hurler & Hunter: Hunter is a milder form of Hurler (remember, hunters need good vision, no corneal clouding)

LIGHTS on RITE by Ahmed Koriesh