inborn errors of metabolism

Question 1

define hypoglycemia in adults, children and infants

Answer 1

adults: glucose <52mg/dl after fasting 24 hrs

Question 2

symptoms of hypoglycemia

Answer 2

irritability, tremor, seizures, decreased level of consciousness or coma.

Question 3

list disorders that cause hypoglycemia in 4-6 hrs

Answer 3

glucose-6-phosphatase deficiency, hyperinsulinism, cortisol/GH deficiency in infants

Question 4

list disorders that cause hypoglycemia in 6-8hrs

Answer 4

cortisol/fatty acid oxidation disorders in infants, milder glycogen storage and gluconeogenic dz, cortisol and GH deficiency in children/adults

Question 5

list disorders that cause hypoglycemia in 10-12hrs

Answer 5

Fatty acid oxidation disorders in older children and adults, Mild disorders of GSD in adults

Question 6

list disorders that cause hypoglycemia in 12-24hrs

Answer 6

ketotic hypoglycemia, Fatty acid oxidation disorders in older children and adults

Question 7

What causes glycogen storage diseases

Answer 7

disorders of glucose release, synthesis or degradation

Question 8

Most severe glycogen storage disease

Answer 8

glucose-6-phosphatase deficiency (GSD1) aka von Gierke disease

Question 9

describe glucose-6-phosphatase deficiency

Answer 9

impairment in glucose release from the liver from glycogenolysis and gluconeogenesis

Question 10

G-6-phosphatase deficiency signs/labs

Answer 10

hepatomegaly, early and severe (<4hr) hypoglycemia, lactic acidosis, hypertriglyceridemia/ hypercholesterolemia, hyperuricemia, short stature, doll like face

Question 11

GSD-1 treatment

Answer 11

constant glucose supply via frequent feeds, nasogastric drip or uncooked cornstarch.

Question 12

List glycogen synthesis disorders

Answer 12

glycogen synthase deficiency (GSD0) or branching enzyme deficiency

Question 13

presentation of glycogen synthase deficiency

Answer 13

•hyperglycemia after a meal, followed by low blood sugar later, increased lactate, and severe ketotic hypoglycemia. Liver is normal in size.

Question 14

Glycogen synthase deficiency treatment

Answer 14

high protein diet to provide gluconeogenesis substrates and low glycemic index complex carbs to minimize post-prandial hyperglycemia and hyperlactacidemia

Question 15

symptoms of branching enzyme deficiency

Answer 15

abnormal glycogen causes tissue damage: progressive liver cirrhosis, cardiomyopathy, hypotonia and muscle weakness, neuropathy.

Question 16

Branching enzyme defiency diagnosis and treatment

Answer 16

pathology on biopsy and enzyme assay in liver. Treatment is supportive

Question 17

List disorders in glycogen breakdown

Answer 17

disorders of Glycogen Phosphorylase (GSD VI), Glycogen Phosphorylase kinase (GSD IX) and debranching enzyme (GSD III)

Question 18

debranching enzyme disorder types

Answer 18

GSD-IIIA: deficiency in liver and muscle (85%). GSD-IIIB: deficiency in liver only (15%)

Question 19

debranching enzyme disorder presentation

Answer 19

initial: hypoglycemia, hepatomegaly, growth retardation, mildy cholesterol elevation. Late: cardiomyopathy, myopathy, polyneuropathy, cirrhosis, tissue damage

Question 20

debranching enzyme deficiency treatment

Answer 20

Continuous glucose, raw cornstarch, to keep BG >70. High protein diet may help myopathy and growth failure

Question 21

symptoms of fructose-1,6-bisphosphatase deficiency

Answer 21

late and mild hypoglycemia, severe lactic acidosis, mild liver enzyme elevation

Question 22

F-1,6-BP defiency treatment

Answer 22

acute: glucose (corrects lactate). Prevention: avoid fasting, use uncooked cornstarch at night, treat hypoglycemia

Question 23

Hereditary fructose intolerance

Answer 23

Due to deficiency in Aldolase B which splits Fructose 1 P into 3 carbon intermediates that can enter glycolysis. Effect is accumulation of fructose 1P which has toxic effects on liver, kidney and brain

Question 24

Hereditary fructose intolerance symptoms

Answer 24

occur with introduction of fruits and other fructose soures in diet in first year of life, but not at birth or in first few months- nausea, vomiting, sweating, lethargy, hypoglycemia, elevated LFTs, liver injury

Question 25

Hereditary fructose intolerance treatment

Answer 25

avoid fructose, sucrose or sorbitol

Question 26

causes of Galactosemia

Answer 26

galactokinase deficiency, aldose reductase deficiency or galactose-1-phosphate uridyltransferase deficiency

Question 27

sypmtoms of galactosemia

Answer 27

hypoglycemia, failure to thrive, hepatomegaly/ cirrhosis, cataracts, mental retardation.

Question 28

treatment of galactosemia

Answer 28

lactose free diet

Question 29

List common inborn errors of fat metabolism

Answer 29

carnitine problems, Acyl CoA dehydrogenase deficits, HMG-CoA synthase/lyase deficits

Question 30

Outcome of decreased fatty acid oxidation

Answer 30

Decreased fat oxidation in liver deprives gluconeogenesis of a source of fuel. Decreased availability of acetyl CoA from fatty acid oxidation and/or ketones makes most tissues obligate glucose utilizers, therefore greatly increasing glucose utilization and predisposing to hypoglycemia.

Question 31

symptoms/labs of decreased fatty acid oxidation

Answer 31

fasting hypoglycemia with low ketones, liver failure, hypotonia. Labs: hypoglycemia, low ketones, elevated CK from exercise induced rhabdomyolysis

Question 32

most common condition of impaired fat oxidation

Answer 32

medium chain acyl CoA dehydrogenase deficiency

Question 33

Additional causes of hypoglycemia

Answer 33

counterregulatory hormone defects: hypopituitarism, GH deficiency, ACTH or cortisol defieicny, beta blockers (decreased epi). Defects in insulin suppression: congenital hyperinsulinism, infant of diabetic mother, latrogenic, insulinoma

Question 34

role of counterregulatory hormones in glucose

Answer 34

maintain glucose levels duriing periods of fasting

Question 35

features of hyperinsulinism in newborn

Answer 35

large for gestational age, excessive IV glucose infusion rate requirement, absence of ketones

Question 36

ketotic hypoglycemia

Answer 36

One of the most common causes of hypoglycemia in childhood. Diagnosis of exclusion. Lack of substrates for gluconeogenesis . Hypoglycemia after fasting 14-24 hours. Presents at 1-5 years old. Spontaneously remits at 8-9 years old

Question 37

labs for hypoglycemia

Answer 37

check blood glucose > if acidotic look for ketones (normal ketotic hypoglycemia, panhypopituitarism, GH/ACTH/cortisol deficiency, GSD 3,6,9,10) or lactate (GSD0, F-D-Pase defieicny, pruvate carboxylase deficiency). If not acidotic check for high FFA (hyperinsulisim or hypopituitarism) or low free fatty acids (fatty acid oxidation disorder or defect in ketogenesis)