Neonatal Hypoglycemia and Neonatal Diabetes Flashcards
(40 cards)
1
Q
Elevated lactate + hypoglycemia =
A
FEG1
- F-1,6-phosphatase deficiency
- EtOH
- GSD1 (Von Gierke’s)
2
Q
Elevated ketones + hypoglycemia =
A
KAGG
- Ketotic hypoglycemia
- AI
- GH deficiency
- GSD 0,3,6,9
3
Q
Low ketones + high FFAs =
A
FAO
4
Q
Low ketones + low FFAs =
A
HHIM
- HI
- Hypopit
- Insulinoma
- Meds
5
Q
Summarize GCK-related hypoglycemia.
A
- Genetics: ACTivating mutation in GCK on chromosome 7
- Labs: BG usually never <50
- Tx: Diazoxide
6
Q
Summarize HIHA.
A
- Genetics: Activating AD mutation in GLUD1 (glutamate dehydrogenase) on chromosome 10
- Labs: Elevated ammonia + hypoglycemia.
- Phenotype: Hypoglycemia after eating protein.
- Tx: Diazoxide.
7
Q
**Hypoglycemia after eating protein = **
A
HIHA (activating AD mutation in GLUD1 on chromosome 10)
8
Q
Summarize HNF1a and HNF4a mutations as a cause of neonatal hyperinsulinism.
A
- Genetics: Inactivating mutations of HNF1a on 12q24 or HNF4a on chromosome 20.
- Causes diabetes in adolescence.
- Tx = diazoxide.
9
Q
Summarize the K+ channel mutations that lead to neonatal hypoglycemia.
A
- Genetics: AR or AD inactivating mutations in ABCC8 on 11p15 (most common) or KCNJ11 on 11p15 (least common). This cause excessive flow of K+ through the K+ channels until they eventually CLOSE –> hypersecretion of insulin –> hypoglycemia.
- Phenotype: If maternally imprinted (expression of father’s allele), you get focal disease. If paternally imprinted (expression of mother’s allele), you get diffuse disease.
- Tx: Most do not respond to diazoxide. Exception is AD diffuse HI.
10
Q
How does diazoxide work and how is it dosed?
A
- Opens K+ channels on pancreatic B-cells by blocking SUR1/outer domain. This leads to hyperpolarization and less insulin is secreted.
- 5-15 mg/kg/d divided bid
11
Q
How does octreotide work?
A
- Somatostatin analogue that works by doing 3 things: 1. inhibiting adenyl cyclase and thus lowering production of cAMP, 2. turns off calcium channels, and 3. stimulates K+ channels.
- In pancreatic B-cells, it will stop calcium from entering cells and thus limit insulin secretion.
- Summary: Inhibits TAIGG release = TSH, ACTH, Insulin, GH, Glucagon
12
Q
What is Wolfram Syndrome?
A
- Genetics: AR mutation in WSF1 on 4p16.
- Phenotype: DIDMOAD = Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, Deafness (sensorineural)
13
Q
What is RCAD?
A
- Genetics: AD activating mutation in HNF1B on chromosome 17. Also associated w/ MODY5. Remember that the D in RCAD looks like B for beta.
- Phenotype: Renal cysts and diabetes mellitus. Also can cause pancreatic insufficiency.
- Tx: Replace pancreatic enzymes.
14
Q
What is IPEX syndrome?
A
- Immunodysregulation polyendocrinopathy enteropathy X-lined.
- Genetics: mutation in FOXP3 on the X-chromosome (thus X-linked).
- Phenotype: T-cell autoimmunity with diabetes mellitus, diarrhea, and eczema.
15
Q
Summarize GATA4 mutations.
A
- Genetics: AR mutation in GATA4.
- Phenotype: Neonatal and childhood onset DM, pancreatic hypoplasia, cardiac defects.
16
Q
Summarize GATA6 mutations.
A
Neonatal diabetes mellitus due to lack of pancreas plus presence of congenital heart disease.
17
Q
neonatal diabetes mellitus due to lack of pancreas =
A
GATA6 mutation
18
Q
Summarize GLIS3 mutations.
A
- Genetics: AR mutation in GLIS3.
- Phenotype: Neonatal diabetes mellitus, congenital hypothyroidism, and glaucoma.
19
Q
neonatal diabetes mellitus + glaucoma =
A
GLIS3 mutation
20
Q
Summarize 6q24 mutations.
A
- Genetics: AD overexpression of paternal PLAG1 or HYMAI from 6q24 most often due to paternal UPD.
- Phenotype: DUMS = Diabetes mellitus, Umbilical hernia, Macroglossia, SGA.
- Most common cause of transient neonatal diabetes mellitus that comes back in adolescence.
- Tx: SU.
21
Q
Summarize mutations in PDX1.
A
- Genetics: AD or AR inactivating mutation of PDX1. Loss of 1 copy of gene (heterozygotes) = MODY4. Loss of both copies (homozygotes) = pancreatic agenesis.
- Phenotype: neonatal diabetes mellitus.
22
Q
Summarize KCNJ and ABCC8 mutations as the cause of diabetes mellitus.
A
- Genetics: 1. AD activating mutation of KCNJ11 (Kir6.2) on 11p15 or 2. AD activating mutation of ABCC8 (SUR1) on 11p15. KCNJ11 mutation is more common. In both cases, K+ channel is always open leading to B-cell hyperpolarization and less insulin secretion.
- Phenotype: DEND = Developmental delay, Epilepsy, Neonatal Diabetes = for patients w/ KCNJ11 mutations.
- KCNJ11 is the most common cause of permanent neonatal diabetes mellitus and the second most common cause of transient neonatal diabetes that can come back in adolescence. When looking at neonatal diabetes overall (transient and permanent), KCNJ11 is the most common cause.
- Tx: SU.
23
Q
Summarize INS mutations.
A
- Genetics: Inactivating mutation in INS gene for insulin on chromosome 11 –> diabetes.
- Can cause transient neonatal diabetes mellitus that comes back in adolescence. Also most second most common cause of permanent neonatal diabetes mellitus.
24
Q
What is Wolcott-Rallison Syndrome?
A
- Genetics: AR mutation in EIF2.
- Phenotype: Neonatal diabetes mellitus, skeletal dysplasia, neutropenia, pancreatic exocrine insufficiency.
- Most common cause of neonatal diabetes mellitus among consanguineous families.
25
neonatal diabetes mellitus in a consanguineous family =
Wolcott-Rallison Syndrome (mutation in EIF2)
26
At what age does neonatal diabetes mellitus present?
<6 mos of life
27
**What are the most common causes of transient neonatal diabetes mellitus in order of incidence?**
"6 Dead Acrobats In Reno"
1. AD paternal overexpression of PLAG1 or HYMAI on 6q24.
2. DEND = AD activating mutation of KCNJ11.
3. AD activating mutation of ABCC8.
4. Inactivating mutation of INS.
5. RCAD (MODY 5) = AD mutation in HNF1B.
28
**What are the most common causes of permanent neonatal diabetes mellitus in order of incidence?**
Dead In Acrobats
1. DEND = AD activating mutation of KCNJ11.
2. Inactivating mutation of INS on chromosome 11
3. AD activating mutation of ABCC8.
29
**What types of neonatal diabetes mellitus respond to sulfonylureas?**
6 Dead Acrobats
- AD paternal overexpression of PLAG1 or HYMAI on 6q24.
- DEND = AD activating mutation of KCNJ11.
- AD activating mutation of ABCC8.
30
What is the abnormal IGF in HI?
Low IGF-BP1
31
When should you start to investigate etiology of hypoglycemia in newborns?
If the newborn continues to have hypoglycemia beyond 48 HOL
32
elevated lipids + elevated uric acid =
GSD1 (Von Gerke's)
33
How can you differentiate GSD1a vs b?
GSD1b patients also present with neutropenia with frequent bacterial infections as a result.
34
What are insulin and C-peptide levels like in exogenous insulin use?
- High insulin levels
- Low C-peptide levels
35
Mutations in which genes cause neonatal hyperinsulinism/hypoglycemia followed by DIABETES in adolescence?
1. HNF1a
2. HNF4a
3. ABCC8
36
For this stupid test, a positive glucagon stimulation test always indicates?
HYPERINSULINISM
37
Regarding age, when do patients with ABCC8 or KCNJ11 mutations causing hyperinsulinism occur?
In the neonatal period (<3 mos of life). Diagnosing these in toddler- or childhood would be very unusual.
38
What is considered a positive glucagon stimulation test?
Rise in BG by at least 30 pts
39
What is hereditary fructose intolerance?
- Genetics: AR mutation in aldolase B, so you cannot metabolize fructose.
- Phenotype: Hypoglycemia, abdominal pain, and vomiting after having sweet foods.
- Tx: Avoid fructose.
40
**What are the BG targets for neonates per PES?**
- < 48 HOL = maintain > 50 mg/dL
- > 48 HOL w/out a BG disorder = maintain > 60 mg/dL
- > 48 HOL + a BG disorder or suspicion for one = maintain > 70 mg/dL
