Term
Newborn presents with jaundice that will not resolve.
Labs show elevated indirect bilirubin, but no measurable direct bilirubin in blood and bile.
You order a biopsy and fine near-normal histology.
What is the pathophysiology of this condition and how to you confirm your diagnosis? |
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Definition
Crigler Najjar type 1
1) Absent Uridine DIphosphate Glucuronyltransferase (UDGT): enzyme critical for bilirubin conjugation
- Buildup up initial substrate can cause brain damage (kernicterus)
2) Can confirm with genotyping or LFTs + direct bilirubin measurment. |
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Term
| How do you treat Crigler Najjar type 1? |
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Definition
Inborn error of metabolism where absent UDGT prevents bilirubin conjugation and leads to hyperbilirubinemia due to indirect bilirubin and risk of irreversible brain damage (Kernicterus)
1) Phototherapy (10-16 hours per day!) to photo-isomerize bilirubin to excreted form.
2) Avoid medications like Bactrim, which displace bilirubin from albumin
3) Gene therapy and hepatocyte transplant are attractive options because of low level of UDGT |
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Term
Newborn child presents with RUQ pain and low birth weight.
Labs reveals elevated succinylacetone, AFP, prolonged PTT/INR, elevated bilirubin and ALT.
What would you expect on histology? How could you further confirm your diagnosis? |
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Definition
Biochemical evidence of liver failure/HCC, along with elevated succinylacetone (tyrosine catabolism metabolite) suggests Tyrosinemia (Deficiency in Fumarylacetoacetate hydrolase)
1) Histology
- Micronodular cirrhosis
- Nonspecific "neonatal" hepatitis
- Dysplasia and/or HCC
2) Diagnosis
- Measure ffumarylacetoacetate hydrolase in skin fibroblasts
- Can genotype and measure organic acids in urine (succinylacetone= diagnostic) |
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Term
| How can you treat the inborn error of metabolism that presents with biochemical evidence of liver failure and/or HCC and low levels of fumarylacetoacetate hydrolase measured in skin fibroblasts? |
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Definition
Tyrosinemia
1) NTBC- plock pathway proximal to accumulation of toxic intermediate metabolites
2) Monitor for HCC
3) Avoid high protein diet (tyrosine accumulation)
4) Liver t/x successful |
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Term
Newborn presents with evidence of cholestasis and chronic hepatitis.
Labs come back and you fine elevated AST/ALT (chronic hepatitis) and conjugated bilirubin. You also notice low WBC count and platelet counts.
What serum test(s) should you run to diagnose this condition and what is its pathophysiology? |
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Definition
Sounds like a-1 Anti-trypsin deficiency.
Histology should show hepatitis, and positive diastase-resistant globules in hepatocytes on PAS.
1) Should find low serum enzyme levels and run serum electrophoresis to demonstrate ZZ phenotype (produces liver disease).
2) Liver disease is not a common manifestation, but can be seen in ZZ phenotype where abnormal protein accumulates in hepatocytes. |
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Term
| How do you treat the inborn error of metabolism that exhibits a characteristic PAS positive, diastase-restistant globule pattern in hepatocytes on histology, with polymerized protein in the ER on EM? |
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Definition
Alpha 1-antitrypsin Deficiency with neonatal cholestasis and chronic hepatitis.
No current treatment for liver disease
- Avoid cigarettes
- Monitor for HCC
- Liver t/x (watch out for MZ phenotype) |
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Term
Newborn presents in a irritated stage, exhibiting poor feeding and asterixis.
His ear-wax exhibits a sweet odor, which is also found in his urine.
What is the pathophysiology/complications of this condition? |
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Definition
Maple Syrup Urine Disease- Must restrict protein intake and monitor serum AA with intercurrent illness
1) Error in BCAA catabolism due to deficiency of BC alpha-ketoacid dehydrogenase (BCKAD) that can lead to irreversible neurological injury via leucine and alpha-keoisocaproic acid accumulation, as well as BCAA load.
2)
- Coma due to cerebral edema
- Progressive neuropsychiatric issues
- Iatrogenic dietary deficiency (protein restriction diet) |
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Term
Newborn presents in irritated state with evidence of apnea and movement disorder.
Labs come back with elevated branched chain AA levels (leucine, isoleucine and valine) in serum and urine.
Liver histology appears normal.
How do you definitively diagnose/treat this condition? |
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Definition
MSUD due to deficiency in BCKAD enzyme for BCAA metabolism.
1) Diagnose with plasmaBCAA and allo-isoleucine
- can measure enzyme in skin fibroblasts or lymphocytes and genotyping.
2) Protein restriction with essential AA supplementation
- Carefully monitor AA levels with intercurrent disease
- Liver transplant successful (Domino transplant form MSUD kid to normal kid after MSUD kid receives liver). |
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Term
Newborn presents with jaundice and coagulopathy. They have developed night blindness and neurological symptoms as well.
Labs reveals elevation in AST/ALT and billirubin with low levels of BA.
How do you diagnose/treat this condition? |
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Definition
Bile acid synthesis defect with accumulation of intermediate metabolites (hepatocyte injury) and absence of end-product (cholestasis)
- See jaundice b/c of bilirubin, coagulopathy because of lack of vitamin K and night blindness because of lack of vitamin A (you might see rickets with lack of vitamin D as well).
1) Diagnose with mass spec for urine bile acid metabolites
- genotyping works for some disorders
2) Treat with primary BA replacement, EADK replacement
- liver t/x if no neural involvement or systemic disease. |
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Term
| Why do newborn patients with bile acid synthesis defects get cirrhosis? |
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Definition
Lack of bile acids prevents absorption of fat soluble vitamins
Hepatocyte injury (intermediate metabolite accumulation) and Cholestasis (no end-product) cause chronic liver injury and poor bile flow, leading to Cirrhosis. |
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Term
| What are the 3 forms of Tyrosinemia and their different clinical presentations? |
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Definition
1) Acute Form: Liver failure prior to 6 months of life
2) Subacute Form: Failure to thrive, hepatomegaly, rickets, renal tubular disease
3) Chronic Form:
- Rickets and hepatomegaly
- Hepatocellular carcinoma
- Porphyria - paresthesias, autonomic dysfunction, paralysis |
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Term
| When is liver transplant indicated in newborns with Tyrosinemia? |
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Definition
1) Acute liver failure
2) Suspicion for HCC
- Growing liver lesion
- AFP that does not normalize or rises |
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Term
| Which kids with liver disease from a1at deficiency should get a t/x? |
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Definition
1) Indicated for decompensated liver disease
- Abnormal coagulation, low albumin levels, elevated bilirubin
- Need to monitor for HCC
**Controversy about MZ phenotype and liver disease - implications for living donor transplantation** |
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