Lysosomal Storage Disorders

Question 1

Pompe Disease

(Type II Glycogen Storage Disease)

Answer 1

• Deficiency: α-1,4-glucosidase (acid maltase)
• Accumulation: Glycogen (in liver, heart, muscle)
• S/Sx: Cardiomegaly, myopathy
• Tx: ERT

Question 2

Fabry Disease

Answer 2

• Category: Sphingolipidoses
• Deficiency: α-galactosidase A
• Accumulation: ceramide trihexoside (glycosphingolipids, globoside)
• S/Sx: X-Linked Recessive, Rash (angiokeratoma), acroparasthesia, extremity pn, eye problems, CV disease, kidney disease
• Tx: ERT

Question 3

Krabbe

(globoid cell leukodystrophy)

Answer 3

• Category: Sphingolipidoses
• Deficiency: galactosylceramide β-galactosidase
• Accumulation: galactocerebroside
• S/Sx: progressive neurologic degeneration
• Tx: none

Question 4

Gaucher

Answer 4

• Category: Sphingolipidoses
• Deficiency: β-glucocerebrosidase (in brain, bone marrow, liver, spleen)
• Accumulation: glucocerebroside
• S/Sx: hepatosplenomegaly, necrosis of femur, neurologic dysfunction, tissue-paper macrophage, bone pn, protruding belly, no coarsening, Type 1 (mild), Type 3 (more severe), Type 2 (most severe)
• Tx: ERT, SRT (Eliglustat, Miglustat)

Question 5

Neimann-Pick

Answer 5

• Category: Sphingolipidoses
• Deficiency: Sphingomyelinase
• Accumulation: sphingomyelin, cholesterol (liver, spleen, lymph)
• S/Sx:
  
  • ​Type A (severe) - death 2-3 y, cherry red spot, foamy macrophage, hepatosplenomegaly, foamy macrophages, psychomotor retardation
  • Type B (mild) - normal intelligence, hepatosplenomegaly

Question 6

Tay-Sachs

(Sandhoff)

Answer 6

• Category: Sphingolipidoses
• Deficiency: hexosaminidase A (Sandhoff is B)
• Accumulation: GM2 ganglioside
• S/Sx: neuro degeneration, cherry red spot on macula, seizures, blindness, death by 5 y/o
• Tx: none

Question 7

Metachromatic Leukodystrophy

Answer 7

• Category: Sphingolipidoses
• Deficiency: Aylsulfatase A
• Accumulation: cerebroside sulfate
• S/Sx: demylination of CNS and PNS, ataxia, dementia

Question 8

Mucopolysaccharidoses

Answer 8

• Common features: ineffective degradation of GAGs (ex. heparin sulfate, chondroitin, etc.)​, Normal development at first, S/Sx appear in childhood
• Gangliosides stored in nerve cells form stacks of membranes (zebra bodies)

Question 9

Sanfilippo (MPS III)

Answer 9

• 4 Enzyme Defects:
  
  • A = Heparan Sulfamidase
  • B = N-Acetylglucosaminidase
  • C = Glucosamine-N-acetyltransferase
  • D = N-Acetylglucosamine-6-sulfatase
• Accumulation: heparan sulfate
• S/Sx: nervous system disorders, mental retardation, hyperactivity, aggressive behavior

Question 10

Morquio (MPS IV)

Answer 10

• Enzyme Deficiency:
  
  • ​A = Galactosamine-6-Sulfatase
  • B = β​-galactosidase
• Accumulation: keratan sulfate
• S/Sx: Short trunk dwarfism, corneal opacities, normal intelligence
• Tx: Vimizim (IV A)

Question 11

Maroteaux-Lamy (MPS VI)

Answer 11

• Defiency: Arylsulfatase B
• Accumulation: Dermatan Sulfate
• S/Sx: normal intelligence, skeletal deformities, large head, cx deformity, corneal clouding
• Tx: Naglazyme

Question 12

Sly (MPS VII)

Answer 12

• Deficiency: β-glucuronidase
• Accumulation: Dermatan and Heparan sulfate
• S/Sx: hepatosplenomegaly, skeletal deformity, short stature, corneal clouding, mental deficiency

Question 13

Hunter (MPS II)

Answer 13

• Deficiency: Iduronate Sulfatase
• Accumulation: Heparin and Dermatan sulfate
• S/Sx: X-Linked Recessive, mental retardation, coarse facial features, short stature, dystosis multiplex, NO CORNEAL CLOUDING
• Tx: Elaprase

Question 14

Hurler (MPS I)

Answer 14

• Deficiency: α-I-iduronasidase
• Accumulation: Dermatan and Heparin Sulfate
• S/Sx: corneal clouding, dysmorphic gargoyle-like facies, hepatosplenomegaly, skeletal abnormalities, mental impairment, chronic rhiniris, hernia, claw hands, conductive deafness, dysostosis multiplex (Hurler-Schie and Schie are less severe - no neuro impairment)
• Tx: Aldurazyme

Question 15

I-Cell Disease (ML II)

Answer 15

• Category: Mucolipidoses
• Deficiency: UDP-NAglucosamine Phosphotransferase (defective enz that synthesizes Man-6-P)
• S/Sx: Coarse face, thick skin/lips, hepatomegaly, joint issues

Question 16

Pseudo-Hurler Polydystrophy (ML-III)

Answer 16

• Category: Mucolipidoses
• Defiency: enz that makes Man-6-P (some residual activity, more mild than I-Cell)
• S/Sx: coarse features, stiffness