MODY

Question 1

MODY 1

Answer 1

• Genetics: AD inactivating mutation in HNF4a on chromosome 20, which is a hepatic transcription factor.
• Tx: Start w/ SU, but will eventually need insulin.

Question 2

MODY 2

Answer 2

• Genetics: AD INactivating mutation in GCK on chromosome 7 (lucky number 7), which is the enzyme that phosphorylates glucose. For MODY2, GCK won’t work until BG is ~135 mg/dL.
• Tx: None.

Question 3

MODY 3

Answer 3

• Genetics: AD mutation in HNF1a or TCF1 on chromosome 12q24, both of which are hepatic transcription factors.
• Tx: Start w/ SUs, but will eventually need insulin.

Question 4

MODY 4

Answer 4

• Genetics: AD INactivating mutation in PDX1 (the number 4 looks like an X when turned sideways) or IPF1 (insulin promoter) on chromosome 13. Loss of 1 copy of gene (heterozygotes) = MODY. Loss of both copies (homozygotes) = pancreatic agenesis.
• Tx = SU.

Question 5

MODY 5

Answer 5

• Genetics: AD mutation in HNF1B or TCF2 on chromosome 17, which are hepatic transcription factors.
• Phenotype: RCAD (renal cysts and diabetes) +/- pancreatic exocrine insufficiency (diarrhea)
• Tx: Insulin.

Question 6

Which MODYs can be treated w/ sulfonylureas?

Answer 6

MODY 1, 3, 4

Question 7

Order the different MODYs in terms of incidence.

Answer 7

1. MODY 3. 50-60%. AD mutation in HNF1a or TCF1.
2. MODY 2. 30%. AD mutation in GCK.
3. MODY 1. <10%. AD mutation in HNF4a.

Question 8

mutation in HNF4a =

Answer 8

MODY1

Question 9

mutation in GCK =

Answer 9

MODY 2

Question 10

mutation in HNF1a or TCF1 =

Answer 10

MODY 3

Question 11

mutation in PDX1 or IPF1 =

Answer 11

MODY 4

Question 12

mutation in HNF1B or TCF2 =

Answer 12

MODY 5

Question 13

What percentage of diabetes mellitus is due to MODY?

Answer 13

2-5%

Question 14

MODY6

Answer 14

• Genetics: AD mutation in NEUROD1
• Phenotype: Diabetes mellitus + neurologic abnormalities
• Tx: Insulin