inborn errors of metabolism Flashcards
define hypoglycemia in adults, children and infants
adults: glucose <52mg/dl after fasting 24 hrs
symptoms of hypoglycemia
irritability, tremor, seizures, decreased level of consciousness or coma.
list disorders that cause hypoglycemia in 4-6 hrs
glucose-6-phosphatase deficiency, hyperinsulinism, cortisol/GH deficiency in infants
list disorders that cause hypoglycemia in 6-8hrs
cortisol/fatty acid oxidation disorders in infants, milder glycogen storage and gluconeogenic dz, cortisol and GH deficiency in children/adults
list disorders that cause hypoglycemia in 10-12hrs
Fatty acid oxidation disorders in older children and adults, Mild disorders of GSD in adults
list disorders that cause hypoglycemia in 12-24hrs
ketotic hypoglycemia, Fatty acid oxidation disorders in older children and adults
What causes glycogen storage diseases
disorders of glucose release, synthesis or degradation
Most severe glycogen storage disease
glucose-6-phosphatase deficiency (GSD1) aka von Gierke disease
describe glucose-6-phosphatase deficiency
impairment in glucose release from the liver from glycogenolysis and gluconeogenesis
G-6-phosphatase deficiency signs/labs
hepatomegaly, early and severe (<4hr) hypoglycemia, lactic acidosis, hypertriglyceridemia/ hypercholesterolemia, hyperuricemia, short stature, doll like face
GSD-1 treatment
constant glucose supply via frequent feeds, nasogastric drip or uncooked cornstarch.
List glycogen synthesis disorders
glycogen synthase deficiency (GSD0) or branching enzyme deficiency
presentation of glycogen synthase deficiency
•hyperglycemia after a meal, followed by low blood sugar later, increased lactate, and severe ketotic hypoglycemia. Liver is normal in size.
Glycogen synthase deficiency treatment
high protein diet to provide gluconeogenesis substrates and low glycemic index complex carbs to minimize post-prandial hyperglycemia and hyperlactacidemia
symptoms of branching enzyme deficiency
abnormal glycogen causes tissue damage: progressive liver cirrhosis, cardiomyopathy, hypotonia and muscle weakness, neuropathy.
Branching enzyme defiency diagnosis and treatment
pathology on biopsy and enzyme assay in liver. Treatment is supportive
List disorders in glycogen breakdown
disorders of Glycogen Phosphorylase (GSD VI), Glycogen Phosphorylase kinase (GSD IX) and debranching enzyme (GSD III)
debranching enzyme disorder types
GSD-IIIA: deficiency in liver and muscle (85%). GSD-IIIB: deficiency in liver only (15%)
debranching enzyme disorder presentation
initial: hypoglycemia, hepatomegaly, growth retardation, mildy cholesterol elevation. Late: cardiomyopathy, myopathy, polyneuropathy, cirrhosis, tissue damage
debranching enzyme deficiency treatment
Continuous glucose, raw cornstarch, to keep BG >70. High protein diet may help myopathy and growth failure
symptoms of fructose-1,6-bisphosphatase deficiency
late and mild hypoglycemia, severe lactic acidosis, mild liver enzyme elevation
F-1,6-BP defiency treatment
acute: glucose (corrects lactate). Prevention: avoid fasting, use uncooked cornstarch at night, treat hypoglycemia
Hereditary fructose intolerance
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
Hereditary fructose intolerance symptoms
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
Hereditary fructose intolerance treatment
avoid fructose, sucrose or sorbitol
causes of Galactosemia
galactokinase deficiency, aldose reductase deficiency or galactose-1-phosphate uridyltransferase deficiency
sypmtoms of galactosemia
hypoglycemia, failure to thrive, hepatomegaly/ cirrhosis, cataracts, mental retardation.
treatment of galactosemia
lactose free diet
List common inborn errors of fat metabolism
carnitine problems, Acyl CoA dehydrogenase deficits, HMG-CoA synthase/lyase deficits
Outcome of decreased fatty acid oxidation
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.
symptoms/labs of decreased fatty acid oxidation
fasting hypoglycemia with low ketones, liver failure, hypotonia. Labs: hypoglycemia, low ketones, elevated CK from exercise induced rhabdomyolysis
most common condition of impaired fat oxidation
medium chain acyl CoA dehydrogenase deficiency
Additional causes of hypoglycemia
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
role of counterregulatory hormones in glucose
maintain glucose levels duriing periods of fasting
features of hyperinsulinism in newborn
large for gestational age, excessive IV glucose infusion rate requirement, absence of ketones
ketotic hypoglycemia
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
labs for hypoglycemia
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)
