9 Genetic Disorders of the GI Flashcards
What is Crigler Najjar due to
Hereditary unconjugated hyperbilirubinemia
Crigler Najar is caused by what enzyme
Absent (Type 1) or low levels (Type 2 ) of hepatic bilirubin UGT (UGT1A1)
When does Crigler Najjar present
Early in life
Why is jaundice seen in premies
They have lower levels of UGT1A1
What does Crigler Najar result in
Brain damage early in infancy
Cancer drug (Ironotecan) gets solubilized by what
UGT1A1 (it attaches a glucose)
What are the symptoms of Crigler Najjar
- neonatal jaundice
- sepsis
- hypotonia
- kernicterus (causes deafness and poor mental progression)
PE
- jaundice
- oculomotor palsy
What are the treatments for Crigler Najjar
- plasmapharesis
- phototherapy
- phenobarbital (UGT1A1 inducer)
the inducer only works in Type 2
What is kernicterus
- bilirubin deposition in the brain
- poor development/mental function
Severe cases die within a few years
What is Gilbert syndrome
Hereditary unconjugated hyperbilirubinemia
What causes Gilbert syndrome
Defect in promotor for UGT1A1
What lab results do we find with Gilbert’s syndrome
Mild decrease in UDP glucuronyl transferase activity
Mild decrease in bilirubin uptake
What symptoms does Gilbert’s syndrome present with
Largely asymptomatic but:
- occasional and recurrent jaundice
- associated with fasting
- stress
- EtOH intake
How do you diagnose Gilbert’s syndrome
Isolated uncojugated hyperbilirubinemia without hepatitis or hemolysis
What is the treatment for Gilbert’s syndrome
None
Prognosis, prevention, and complications
Avoid Irinotecan
Black liver
Dubin-Johnson syndrome
What are the symptoms of Dubin-Johnson/Rotor’s syndrome
Hereditary conjugated hyperbilirubinemia
Causes deceased hepatic excretion of conjugated bilirubin
Why is DJS liver black
Impaired excretion of epinephrine metabolites (MRP2 deficiency)
What are the PE findings of DJS and Rotor’s syndrome
May become jaundiced or icteric during pregnancy or with oral contraceptives
DJS and rotor’s syndrome may have what lab values
Direct hyperbilirubinemia and increased total bilirubin in DJS
How can you distinguish DJS and Rotor
Elevated urine coproporphyrin levels in Rotors
Normal in DJS
What causes the symptoms of Wilson’s disease
Free copper accumulation in many tissues
What causes Wilson’s disease
ATP7B
What does ATP7B do
Uses ATP to pump copper into bile and plasma
Defective in Wilson’s disease
What are the symptoms of Wilson’s disease
- parkinson’s like symptoms
- hemiballismus - flailing, ballistic, undesired movements of the limbs
- dementia
What do you find with Wilson’s disease on physical exam
Cirrhosis and corneal deposits (Kayser Fleischer rings)
They are rarely seen outside of Wilson’s
What are the labs that are found with Wilson’s
- decreased total serum copper
- increased non-ceruloplasmin bound copper
- increased urine/serum free copper
- hemolytic anemia
What is the medical treatment for Wilson’s disease
Ammonium tetrathiomolybdate —>urinary excretion of copper
Penicillamine —> copper chelator
Tientine —> copper chelator
Zinc —> competes with copper for absorption in the gut via ATPB7
What are the surgical treatments of Wilson’s disease
Consider liver transplantation as clinical condition deteriorates
Wilson’s disease is also at risk foir
- hepatitis
- cirrhosis
- hepatocellular carcinoma
- Fanconi’s disease
