Glycogen Storage Disorders & Peroxisomal Disorders

Von Gierke

(GSD-I)

• Gene(s): G6PC, SLC37A4

• Inheritance Pattern: AR

• Feature(s):

  • most common GSD

  • doll-like facies

  • glycogen accumulation in the liver and kidneys

  • severe fasting hypoglycemia

  • hyperlipidemia

  • lactic acidosis

  • hepatomegaly

• Treatment(s):

  • high-protein, low-fat diet

  • uncooked starch

  • high-carbohydrate meals

Pompe disease

(GSD-II)

• Gene(s): GAA

• Inheritance Pattern: AR

• Feature(s):

  • cardiomyopathy

  • skeletal muscle weakness

  • death by 20s in infantile/childhood forms

• Treatment(s):

  • ERT

McArdle disease

(GSD-5)

• Gene(s): PYGM

• Inheritance Pattern: AR

• Feature(s):

  • exercise intolerance

  • muscle cramps, weakness, and fatigue

  • diagnosis is often delayed due to clinical heterogeneity and difficulty recognizing certain diagnostic phenomena

• Treatment(s):

  • aerobic training

  • high carbohydrate diet (especially before exercise)

Zellweger syndrome

(peroxisomal disorder)

• Gene(s): PEX (especially PEX1)

• Inheritance Pattern: AR

• Feature(s):

  • death by 1-2

  • craniofacial dysmorphisms: high forehead, large anterior fontanelle, ear deformities, epicanthal folds

  • developmental delay

  • seizures and/or structural brain abnormalities

  • retinitis pigmentosa, corneal clouding, cataracts, glaucoma

  • hepatomegaly

  • chondrodysplasia punctata

• Treatment(s):

  • no cure (symptomatic-based/surveillance treatments)

X-linked adrenoleukodystrophy

(peroxisomal disorder)

• Gene(s): ABCD1

• Inheritance Pattern: X-linked

• Feature(s):

  • ~65-80% of females can develop symptoms (slower disease progression, adrenal insufficiency is rare)

  • childhood cerebral ALD: presents at ~7 years; behavioral changes (aggressive or disinhibited behavior); progressive neurologic dysfunction; adrenal insufficiency

  • adreno-myelo-neuropathy: onset is typically in adulthood; sexual dysfunction

• Treatment(s):

  • Skysona (gene therapy)

  • adrenal hormonal replacement