Inborn Errors: Glycolipid Disorders

Question 1

Gaucher Type I: inheritance

Answer 1

Autosomal recessive

Question 2

Gaucher Type I: enzyme deficiency

Answer 2

Beta-glucosidase (glucocerebrosidase)

Question 3

Gaucher Type I: presentation

Answer 3

• Adult onset
• Bony pain (avascular necrosis)
• Hepatosplenomegaly
• Anemia
• Thrombocytopenia
• Normal intellect
• Restrictive lung disease
• Gaucher cells (macrophages) in bone marrow

Question 4

Gaucher Type I: organs involved/untreated survival

Answer 4

• Skeleton, liver, spleen, bone marrow
• No CNS involvement
• Will live normal life span

Question 5

Gaucher Type I: key features

Answer 5

• Treatment available
• Adult onset
• Big liver/spleen
• Anemia/low platelets
• Increased incidence in Ashkenazi Jews
• Erlenmeyer flask deformity on X-ray
• “Crumped tissue paper” histology

Question 6

Tay Sachs Type I: inheritance

Answer 6

Autosomal recessive

Question 7

Tay Sachs Type I: enzyme deficiency

Answer 7

Beta-hexosaminidase A

Question 8

Tay Sachs Type I: presentation

Answer 8

• Infantile
• Blindness, seizures, mental and motor deterioration

Question 9

Tay Sachs Type I: organs involved/untreated survival

Answer 9

• Mainly CNS involvement
• Will die

Question 10

Tay Sachs Type I: key features

Answer 10

• Cherry red spot in eye (classic)
• Increased startle reflex
• Normal liver/spleen

Question 11

Fabry disease: inheritance

Answer 11

X-linked (females have delayed disease)

Question 12

Fabry disease: enzyme deficiency

Answer 12

Alpha-galactosidase

Question 13

Fabry disease: presentation

Answer 13

• Childhood: acroparesthesias
• Young adult: proteinuria, angiokeratomas (skin)
• Renal failure, death at 4th decade
• Cardiac disease (hypertrophy) if renal disease treated
• Chronic irritable bowel

Question 14

Fabry disease: organs involved/untreated survival

Answer 14

• Nervous system, skin, renal, cardiac, eye
• Death in males ~age 40 if untreated
• Women have delayed onset

Question 15

Fabry disease: key features

Answer 15

• Treatment available
• Angiokeratomas (bathing trunk distribution)
• Renal failure
• Acroparesthesias (pain in palms and soles)
• Normal IQ

Question 16

Pompe Disease: inheritance

Answer 16

Autosomal recessive

Question 17

Pompe Disease: enzyme deficiency

Answer 17

Alpha-glucosidase

Question 18

Pompe Disease: presentation

Answer 18

• Infantile: major muscle weakness, hypertrophic cardiomyopathy
• Adult: gradual proximal muscle weakness with normal heart and respiratory failure

Question 19

Pompe Disease: organs involved/untreated survival

Answer 19

• Skeletal muscles, heart
• Infantile onset will die

Question 20

Pompe Disease: key features

Answer 20

• Treatment available
• Infant with profound weakness and hypertrophic cardiomyopathy OR
• Adult with proximal muscle weakness and sleep apnea

Question 21

Hunter syndrome: inheritance

Answer 21

X-linked (females have no disease)

Question 22

Hunter syndrome: enzyme deficiency

Answer 22

Iduronate sulfatase

Question 23

Hunter syndrome: presentation

Answer 23

• Children:
  
  • Growth
  • Coarse facies
  • Airway disease
  • Cognitive decline
  • Heart valve problems
  • Macroglossia
  • Hoarse voice
  • Hearing loss
  • Hepatosplenomegaly

Question 24

Hunter syndrome: organs involved/untreated survival

Answer 24

• Growth, skeleton, skin, airway, CNS, heart, liver, spleen, corneal disease
• Severe cases will die

Question 25

Hunter syndrome: key features

Answer 25

* Treatment available * Coarse-appearing, short child with hoarse voice * Frequent URIs * Some learning problems * NO corneal clouding

Question 26

Hurler syndrome: inheritance

Answer 26

Autosomal recessive

Question 27

Hurler syndrome: enzyme deficiency

Answer 27

Alpha-iduronidase

Question 28

Hurler syndrome: presentation

Answer 28

* Looks a bit like Hunter BUT girls affected also * Growth * Coarse facies * Airway disease * Hearing loss * Significant cognitive decline * Dysostosis multiplex

Question 29

Hurler syndrome: organs involved/untreated survival

Answer 29

* Growth, skeleton, skin, airway, CNS, heart, liver, spleen, corneal disease * Severe cases will die

Question 30

Hurler syndrome: key features

Answer 30

* Treatment available * Similar to Hunter (can occur in girls) * Coarse facies * Big liver/spleen * Major skeletal problems * _Corneal clouding_

Question 31

McArdle Disease: inheritance

Answer 31

Autosomal recessive

Question 32

McArdle Disease: enzyme deficiency

Answer 32

Glycogen phosphorylase

Question 33

McArdle Disease: presentation

Answer 33

* Muscle weakness and cramping * Normal liver enzymes * Normal cognition * Chronic condition * Myoglobinuria (coffee-colored urine after exercise)

Question 34

McArdle Disease: organs involved/untreated survival

Answer 34

* Muscles

Question 35

McArdle Disease: key features

Answer 35

* Muscle cramping after exercise * Myoglobinuria (coffee colored urine after exercise)

Question 36

Niemann-Pick type A/B: inheritance

Answer 36

Autosomal recessive

Question 37

Niemann-Pick type A/B: enzyme deficiency

Answer 37

Sphingomyelinase

Question 38

Niemann-Pick type A/B: presentation

Answer 38

* Type A: severe with CNS * Type B: non-neuropathic * Major hepatosplenomegaly * Xanthomas in skin * Cherry red spot * Supranuclear palsy (vertical gaze palsy) * Corneal opacities * Anemia * Coronary artery disease

Question 39

Niemann-Pick type A/B: organs involved/untreated survival

Answer 39

* Systemic: CNS (type A), liver, spleen, skin, eye, growth, bone marrow, respiratory, cardiovascular * Type A likely to die early

Question 40

Niemann-Pick type A/B: key features

Answer 40

* Supranuclear gaze palsy * Cherry red spot * BIG hepatosplenomegaly