GI,Hepatobiliary,Pancreas

Question 1

Hirschsprung disease structural chromosomal abnormality.

Answer 1

Trisomy 21 (10% of cases)

Question 2

Syndromes ass. w/ Hirschsprung.

Answer 2

• NF1
• MEN2A
• Waardenburg syndrome
• Congenital Central Hypoventilation (Haddad)
• Familial Dysautonomia (Riley-Day)
• Smith-Lemli-Opitz syndrome

Question 3

Osler-Weber-Rendu syndrome inheritance/mutation.

Answer 3

• Autosomal Dominant

- ENG gene or ACVRL1 gene

Question 4

Osler-Weber-Rendu syndrome features.

Answer 4

• Epistaxis (Children)
• Skin lesions (Adolescence)
• GI bleeding (Adults)

Question 5

MCC of malabsorption in neonatal period.

Answer 5

Microvillus Inclusion Disease (MDD)

Question 6

Microvillus Inclusion Disease (MDD) features.

Answer 6

• Autosomal Recessive
• Wall of sm. bowel is “paper thin” with villous blunting
• Intracellular inclusions (PAS, CEA, CD10 Positive)

Question 7

MC location of Intestinal Atresia.

Answer 7

Ileum

Question 8

Intestinal Atresia inheritance.

Answer 8

• 30% ass. w/ Down Syndrome.

- Most are isolated defects.

Question 9

Gastroschisis is strongly associated with what?

Answer 9

DECREASED maternal age

Question 10

Gastroschisis has very high levels of what?

Answer 10

Maternal Serum AFP

Question 11

Gastroschisis vs. Omphalocele:

-Located midline, essentially within the umbilicus

Answer 11

Omphalocele

Gastroschisis is to the Right of the umbilicus

Question 12

Gastroschisis vs. Omphalocele:

-Typically an Isolated Defect

Answer 12

Gastroschisis

(Omphalocele is associated with major cardiac defects, chromosomal abnormalities (trisomies 21, 18, 13), or Beckwith-Wiedman syndrome

Question 13

Which HLA allele is associated with Celiac Sprue?

Answer 13

-HLA-DQ2 (~95%) (30% of general population)

Question 14

Caroli disease mutation.

Answer 14

PKHD1 gene on chr6p (same as ARPKD)

Question 15

Caroli disease features.

Answer 15

• Segmental dilation of the intrahepatic bile ducts
• Recurrent stone formation
• Bacterial cholangitis

Question 16

Alagille syndrome inheritance/mutation.

Answer 16

• Autosomal Dominant

- JAG1 gene

Question 17

Alagille syndrome features.

Answer 17

• Dysmorphic features
• Noninflammatory LOSS of interlobular BILE DUCTS
• Cholestasis (neonatal period)

Question 18

Hereditary Hemochromatosis (HH) inheritance/ mutation.

Answer 18

• Autosomal Recessive

- HFE gene located within the MHC region on chr6p

Question 19

MC clinically significant mutation in HH.

Answer 19

-C282Y

2nd MC is H63D; found in 25% of whites

Question 20

T/F: Men are 2X more likely to develop complications of HH.

Answer 20

True

-Example of Autosomal Recessive condition with variable penetrance

Question 21

Pathophysiology of Hereditary Hemochromatosis.

Answer 21

• Enhanced Intestinal Iron Absorption
• Low HEPCIDIN levels
• Iron deposition within hepatocytes, pancreas, pituitary, etc.
• Cirrhosis
• Pancreatic Fibrosis (DM)
• Hypogonadotrophic Hypogonadism
• Infertility
• Osteoarthritis
• Cardiomyopathy
• BRONZE SKIN

Question 22

Wilson Disease (Hepatolenticular Degeneration) inheritance/mutation.

Answer 22

• Autosomal Recessive

- ATP7B gene (encodes an ATPase utilized in copper binding to ceruloplasmin)

Question 23

Wilson disease presentation.

Answer 23

• Liver disease
• Neuropsychiatric (Kayser-Fleischer rings)
• Hemolysis

Question 24

Wilson disease Liver Biopsy findings:

Answer 24

• Glycogenated nuclei
• Steatosis
• Inflammation (similar to chronic viral hepatitis)
• Ultimately Cirrhosis

Question 25

Wilson disease Lab findings.

Answer 25

-LOW Ceruloplasmin - HIGH urinary Copper excretion * Serum Copper is UNRELIABLE

Question 26

Alpha1-Antitrypsin (AAT) deficiency inheritance/gene/chr.

Answer 26

- Autosomal Recessive - SERPINA1 (P1) gene on chr14 (Polymorphic)

Question 27

Most healthy adults are homozygous for which SERPINA1 gene allele?

Answer 27

M allele (Pi-MM)

Question 28

AAT deficiency is usually caused by what SERPINA1 genotype?

Answer 28

-Z allele (Pi-ZZ) or Pi-ZS

Question 29

Bilirubin Excretion disorder subclasses.

Answer 29

- Conjugation disorders | - Secretion disorders

Question 30

What are the two Bilirubin Conjugation disorders?

Answer 30

- Gilbert syndrome | - Crigler-Najjar syndrome

Question 31

What are the two Bilirubin Secretion disorders?

Answer 31

- Dubin-Johnson syndrome | - Rotar syndrome

Question 32

Gene involved in Bilirubin Conjugation disorders?

Answer 32

-UGT1A1 gene

Question 33

What enzyme is deficient in the Bilirubin Conjugation disorders (Gilbert and Crigler-Najjar)? What does this lead to?

Answer 33

- Bilirubin Glucoronosyltransferase | - Increased Unconjugated bilirubin

Question 34

Gilbert syndrome mutation.

Answer 34

5' TATA box in UGT1A1 promoter (5% of pop.) Mildly deficient bilirubin conjugation

Question 35

Type I Vs. Type II Crigler-Najjar: | -NO glucoronosyltransferase activity.

Answer 35

Type I | Type II has <10% of normal

Question 36

Pathophysiology of Dubin-Johnson and Rotor syndromes.

Answer 36

- Defective secretion of conjugated bilirubin into the canaliculus. - Mild Conjugated hyperbilirubinemia

Question 37

Dubin-Johnson mutation.

Answer 37

MRP2 (multidrug resistance protein 2) gene

Question 38

Main difference between Dubin-Johnson and Rotar syndrome.

Answer 38

Rotar syndrome does NOT have Pigmentated Hepatic Parenchyma

Question 39

Cystic Fibrosis gene/mutation.

Answer 39

-CFTR gene on chr7 | chloride channel expressed in respiratory, GI, Skin, Hepatobiliary, Pancreas, Vas Deferens

Question 40

T/F: CF is the most common Autosomal Recessive condition in Whites.

Answer 40

True | -carrier frequency is 1 in 25 (affects 1 in 2,000 births)

Question 41

What syndrome is ass. w/ Autosomal Dominant Pancreatitis and Bone Marrow failure.

Answer 41

Pearson syndrome

Question 42

Pearson syndrome genetics.

Answer 42

Chromosomal breakage syndrome affecting the Mitochondrial DNA (microdeletion within the mtDNA)

Question 43

Syndrome characterized by marrow failure and pancreatic insufficiency. The pancreas shows fatty metamorphosis with preservation of pancreatic islets.

Answer 43

Shwachman-Diamond Syndrome | SBDS gene

Question 44

Syndrome characterized by hypoplasia of the nasal alae, pancreatic exocrine insufficiency with pancreatic lipomatosis, hypothyroidism, and deafness.

Answer 44

Johnason-Blizzard syndrome