Inborn Errors: Glycolipid Disorders Flashcards
Note that Bessessen will NOT ask about specific enzyme names
Gaucher Type I: inheritance
Autosomal recessive
Gaucher Type I: enzyme deficiency
Beta-glucosidase (glucocerebrosidase)
Gaucher Type I: presentation
- Adult onset
- Bony pain (avascular necrosis)
- Hepatosplenomegaly
- Anemia
- Thrombocytopenia
- Normal intellect
- Restrictive lung disease
- Gaucher cells (macrophages) in bone marrow
Gaucher Type I: organs involved/untreated survival
- Skeleton, liver, spleen, bone marrow
- No CNS involvement
- Will live normal life span
Gaucher Type I: key features
- 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
Tay Sachs Type I: inheritance
Autosomal recessive
Tay Sachs Type I: enzyme deficiency
Beta-hexosaminidase A
Tay Sachs Type I: presentation
- Infantile
- Blindness, seizures, mental and motor deterioration
Tay Sachs Type I: organs involved/untreated survival
- Mainly CNS involvement
- Will die
Tay Sachs Type I: key features
- Cherry red spot in eye (classic)
- Increased startle reflex
- Normal liver/spleen
Fabry disease: inheritance
X-linked (females have delayed disease)
Fabry disease: enzyme deficiency
Alpha-galactosidase
Fabry disease: presentation
- Childhood: acroparesthesias
- Young adult: proteinuria, angiokeratomas (skin)
- Renal failure, death at 4th decade
- Cardiac disease (hypertrophy) if renal disease treated
- Chronic irritable bowel
Fabry disease: organs involved/untreated survival
- Nervous system, skin, renal, cardiac, eye
- Death in males ~age 40 if untreated
- Women have delayed onset
Fabry disease: key features
- Treatment available
- Angiokeratomas (bathing trunk distribution)
- Renal failure
- Acroparesthesias (pain in palms and soles)
- Normal IQ
Pompe Disease: inheritance
Autosomal recessive
Pompe Disease: enzyme deficiency
Alpha-glucosidase
Pompe Disease: presentation
- Infantile: major muscle weakness, hypertrophic cardiomyopathy
- Adult: gradual proximal muscle weakness with normal heart and respiratory failure
Pompe Disease: organs involved/untreated survival
- Skeletal muscles, heart
- Infantile onset will die
Pompe Disease: key features
- Treatment available
- Infant with profound weakness and hypertrophic cardiomyopathy OR
- Adult with proximal muscle weakness and sleep apnea
Hunter syndrome: inheritance
X-linked (females have no disease)
Hunter syndrome: enzyme deficiency
Iduronate sulfatase
Hunter syndrome: presentation
- Children:
- Growth
- Coarse facies
- Airway disease
- Cognitive decline
- Heart valve problems
- Macroglossia
- Hoarse voice
- Hearing loss
- Hepatosplenomegaly
Hunter syndrome: organs involved/untreated survival
- Growth, skeleton, skin, airway, CNS, heart, liver, spleen, corneal disease
- Severe cases will die
Hunter syndrome: key features
- Treatment available
- Coarse-appearing, short child with hoarse voice
- Frequent URIs
- Some learning problems
- NO corneal clouding
Hurler syndrome: inheritance
Autosomal recessive
Hurler syndrome: enzyme deficiency
Alpha-iduronidase
Hurler syndrome: presentation
- Looks a bit like Hunter BUT girls affected also
- Growth
- Coarse facies
- Airway disease
- Hearing loss
- Significant cognitive decline
- Dysostosis multiplex
Hurler syndrome: organs involved/untreated survival
- Growth, skeleton, skin, airway, CNS, heart, liver, spleen, corneal disease
- Severe cases will die
Hurler syndrome: key features
- Treatment available
- Similar to Hunter (can occur in girls)
- Coarse facies
- Big liver/spleen
- Major skeletal problems
- Corneal clouding
McArdle Disease: inheritance
Autosomal recessive
McArdle Disease: enzyme deficiency
Glycogen phosphorylase
McArdle Disease: presentation
- Muscle weakness and cramping
- Normal liver enzymes
- Normal cognition
- Chronic condition
- Myoglobinuria (coffee-colored urine after exercise)
McArdle Disease: organs involved/untreated survival
- Muscles
McArdle Disease: key features
- Muscle cramping after exercise
- Myoglobinuria (coffee colored urine after exercise)
Niemann-Pick type A/B: inheritance
Autosomal recessive
Niemann-Pick type A/B: enzyme deficiency
Sphingomyelinase
Niemann-Pick type A/B: presentation
- 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
Niemann-Pick type A/B: organs involved/untreated survival
- Systemic: CNS (type A), liver, spleen, skin, eye, growth, bone marrow, respiratory, cardiovascular
- Type A likely to die early
Niemann-Pick type A/B: key features
- Supranuclear gaze palsy
- Cherry red spot
- BIG hepatosplenomegaly
