155b - Approach to the Newborn with Suspected Liver Disease

Question 1

What causes brain damage in Crigler-Najjar syndrome Type 1?

Answer 1

Very high levels of unconjugated bilirubin

Question 2

Which protein is affected in each progressive familial intrahepatic cholestasis?

How are they treated?

Answer 2

All of the PFICs prevent components of bile from reaching the bile canaliculus

• PFIC-1 - FIC (for A-minophospholipids)
• PFIC-2 - BSEP (for B-ilesalts)
• PFIC-3 - MDR3 (for P-hosphatidylcholine)

Think about what they transport to bile canaliculi alphabetically

Question 3

Which cause of neonatal cholestasis is associated with granular bile?

Answer 3

PFIC-1

• Progressive familial intrahepatic cholestasis - 1
• Deficiency of FIC1

Question 4

Buildup of succinylacetone is characteristic of which metabolic disease?

Answer 4

Tyrosinemia

(due to fumarylacetoacetate hydrolase)

Question 5

What causes Alagille’s syndrome?

Describe the presentation

Answer 5

Defect in Cr 20 in Jagged 1 gene

• > Disrupted NOTCH signaling
• > recuced intralobular bile ducts
• Jaundice
• Hyperbilirubinemia (conjugated)
• Vascular abnormalities
• Cirrhosis
• Characteristic facial features

Question 6

Which congenital liver disease is associated with a defect in the NOTCH signaling pathway?

Answer 6

Alagille’s syndrome

-> reduced/narrow intralobular bile ducts

Question 7

Which genetic disease would cause mucin plugs in bile ducts?

Answer 7

Cystic fibrosis

Question 8

Why does portal HTN develop in cholestasis?

Answer 8

Increased intrahepatic pressure

Question 9

Child with rickets, coagulopathy, night blindness, and neuropathy.

What diagnosis would explain all of the symptoms?

Answer 9

Cholestasis

• Impaired bile excretion
• -> Can’t absorb fat
• -> Can’t absorb ADEK

Question 10

List 3 congenital disorders of bilirubin metabolism

Which gene is affected in each?

Answer 10

• Gilbert: promoter region of UDP-GT
• Crigler-Najjar: UDP-GT
  
  • Type 1 = complete absence -> most severe
  • Type 2 = partial activity
• Dubin Johnson syndrome: cMOAT/MRP2

Question 11

What pediatric disorder would cause formation of multiple bile ducts?

What is the treatment?

Answer 11

Biliary atresia

• Inflammatory or embryonic process -> fibrosis of extrahepatic bile ducts
• Liver compensates by making more

Treatment - hepatic portoenterostomy to restore bile flow

Liver transplantation if there is already damage

Question 12

What is the most common cause of pediatric liver transplantation?

Answer 12

Biliary atresia

Question 13

Which metabolite builds up in tyrsoinemia?

Answer 13

Succinylcetone (urine or serum)

• Will also have elevated serum tyrosine and methionine

Question 14

What are the possible etiologies of biliary atresia? (2)

Answer 14

• Embryonic
  
  • Biliary atresia splenic malformation
• Inflammatory
  
  • Perinatal viral infection -> inflammation against bile ducts

Both result in progressive fibrosis against the bile ducts

Question 15

When is neonatal jaundice abnormal? (4)

Answer 15

• Development before 36h
• Persistence beyond 10 days
• Serum bilirubin >12 mg/dL at any time
• Elevation of the direct (unconjugated) bilirubin to >2 mg/dL at any time
  
  • Or >15% of total bilirubin

Question 16

Why should a choledochal cyst be removed if found?

Answer 16

Risk of cholangiocarcinoma

• If suspected, confirm with ultrasound
• 2/3 will present before age 6, but presentation later in life also possible
  
  • Abd pain, jaundice, palpable RUQ mass