Metabolic/genetics
A 7-day-old full-term female infant is brought to the emergency department with poor feeding, vomiting, and progressive lethargy over the past 3 days. Breast fed.
Jaundiced, lethargic, and hypotonic, hepatomegaly Bilirubin total 14, direct 8
AST: 320, ALT: 280
INR: 2.1
BCx EColi
What disease do they have and what do you do?
Galactossemia
Clues: E. coli sepsis, jaundice, vomiting after milk feeding. Eliminate lactose/galactose from diet immediately (soy formula)
Lactose ingestion
Send urine reducing substances
Newborn screen later returns + deficient GALT enzyme activity
Toxic accumulation of Gal-1-P and galactitol
Can have cataracts in first two weeks of life
A 5-month-old infant with biliary atresia underwent deceased donor liver transplantation 4 days ago. The immediate post-op course was initially stable with good graft function:
On postoperative day 4, the infant develops:
Physical exam: lethargic infant with abdominal tenderness. No obvious bile leak from drains
What study to get and what is main concern?
What is the definition of MASLD?
Hepatic steatosis plus evidence of metabolic dysfunction (overweight/obesity, T2DM, or metabolic risk factors) without significant alcohol or secondary causes
Define pediatric acute liver failure (PALF).
elevated INR ≥ 1.5 with encephalopathy OR INR ≥ 2.0 regardless of encephalopathy in a patient without known chronic liver disease.
What is the key defect/biochemical abnormality in Wilson disease?
Impaired copper excretion due to ATP7B mutation → copper accumulation in liver, brain, cornea
What is the major hepatic complication of untreated tyrosinemia type I and what is the treatment?
Hepatocellular carcinoma and acute liver failure. Nitisinone (NTBC) + dietary restriction of tyrosine/phenylalanine
A 15-year-old boy is evaluated for elevated liver enzymes. Labs:
Proceed with hepatic copper quantification via liver biopsy OR confirmatory ATP7B genetic testing (do not exclude Wilson disease based on absence of KF rings).
Most accurate noninvasive imaging modality for hepatic fat quantification?
MRI-PDFF
What is the most important treatable infectious cause of PALF in children?
Herpes simplex virus (HSV), especially in neonates.
Gene in Wilson disease?
Impaired copper excretion due to ATP7B mutation → copper accumulation in liver, brain, cornea
What is the genetic inheritance pattern of alpha-1 antitrypsin deficiency (and name of the gene)?
SERPINA1 gene. Codominant
A 10-year-old with known cirrhosis due to biliary atresia presents with hematemesis. Endoscopy shows large esophageal varices, which are banded successfully.
What is the most appropriate long-term secondary prophylaxis?
Nonselective beta-blocker therapy + repeat endoscopic variceal ligation.
What patients should be screened for MASLD and how?
Screen with ALT starting at age 9–11 years in children with obesity or overweight plus additional risk factors (e.g., insulin resistance, dyslipidemia, family history of T2DM/MASLD).
What is the most common identifiable cause of PALF in developed countries?
Indeterminate (idiopathic) acute liver failure.
What is a key clue for Wilson disease presenting as PALF?
Low alkaline phosphatase relative to bilirubin, Coombs-negative hemolytic anemia, low ceruloplasmin.
What liver finding is typical of glycogen storage disease type I?
What enzyme is deficient in glycogen storage disease type I?
What is the hallmark metabolic abnormality in glycogen storage disease type I?
Hepatomegaly, hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia
Glucose-6-phosphatase
Severe fasting hypoglycemia
A 7-year-old has splenomegaly and thrombocytopenia but normal liver synthetic function. Ultrasound shows patent portal vein with cavernous transformation. Liver enzymes are normal.'=
AND what to do?
Extrahepatic portal vein obstruction (EHPVO)
12-year-old boy with BMI 99th percentile has persistent ALT 110–130 U/L for 12 months. He has negative workup for viral hepatitis, Wilson disease, and autoimmune hepatitis. Platelets and albumin are normal. Elastography suggests increased stiffness.
According to pediatric guideline principles, what is the most appropriate next step?
Consider liver biopsy to assess severity and stage fibrosis.
Biopsy is considered when:
What is the hallmark lab pattern of acetaminophen toxicity in PALF?
Very high AST/ALT (>1000–10,000), relatively low bilirubin early
What is first-line treatment for Wilson disease?
Chelation therapy (D-penicillamine or trientine) + zinc
What is the diagnostic test of choice for suspected fatty acid oxidation disorders?
What fasting-related risk is most dangerous in fatty acid oxidation disorders?
What is the long-term management principle in fatty acid oxidation disorders?
Plasma acylcarnitine profile + urine organic acids
Hypoglycemia without ketones (hypoketotic hypoglycemia)
Avoid fasting, high carbohydrate intake, carnitine supplementation (selected cases)
A 12-year-old with portal hypertension due to congenital hepatic fibrosis has:
A surgeon recommends splenectomy to improve platelet count prior to elective orthopedic surgery.
What is the most appropriate concern with this plan?
Most common genetic variant associated with increased MASLD risk?
PNPLA3 polymorphism
A 3-year-old boy presents with fever, vomiting, and lethargy for 2 days. Labs show:
Viral hepatitis studies are pending. He has no prior history of liver disease.
You notice marked hypoglycemia and lactic acidosis out of proportion to transaminase elevation pattern.
What is the most likely diagnosis, and what is the most important immediate management step?
Mitochondrial fatty acid oxidation disorder (or other inborn error of metabolism) → immediate high-rate dextrose infusion and avoidance of fasting/catabolism.
A 14-year-old boy presents with 5 days of jaundice, confusion, and dark urine. He is otherwise healthy with no prior liver disease. Labs show: AST 980 U/L, ALT 620 U/L, total bilirubin 26 mg/dL (direct 12), INR 3.0, and hemoglobin 7.8 g/dL with Coombs-negative hemolytic anemia. Serum ceruloplasmin is 9 mg/dL. ALP is 48 U/L (low-normal). The ALP:total bilirubin ratio is 1.8. You strongly suspect Wilson disease–associated acute liver failure.
He is started on penicillamine and transferred for transplant evaluation. Over the next 24 hours, his mental status worsens and INR rises to 3.8.
The team asks: Should we continue aggressive chelation and wait for response before listing for transplant?
Transplant
Reason chelation slow, mental status, INR worsening