Inborn Errors Metabolism Flashcards
At presentation, general way to distinguish between
metabolic disorders with intoxication affects vs
metabolic disorders with energy deficiencies
metabolic disorders with intoxication effects initially asymptomatic
metabolic deficiencies with energy deficiencies usually symptomatic at birth
Why might you see transient neonatal hyperammonemia in preterm infants?
immature N-acetylglutamate synthase activity.
If there is hyperammonemia, what do you assess for?
Acidosis and ketonuria
If acidosis and Ketonuria possible causes?
can be various acidemias, Pyruvate carboxylase deficiency, or B-methlcrtonyl glycinuria
If elevated ammonia with no acidosis, no ketonuria, what do you assess for next?
Plasma citrulline levels
(urea cycle defect?)
If elevated ammonia, with acidosis and ketonuria, what is it?
Fatty acid oxidation abnormality.
In unexplained hypoglycemia what’s next laboratory assessment
Assess for non-gluose reducing substances
If non-glucose reducing substances are absent in hypoglycemia, what is next lab assessment?
check for urine ketones
What lab abnormality will you see in Fatty acid oxidation defect?
increased free fatty acids
(there will be no acidosis)
hypoketotic, hypoglycemia
Galactose-1-phosphate-uridyl transferase (GALT) absent what is disorder?
Classic Galactosemia
Why are there cataracts in galactosemia?
fetal exposure to galactose, excess galacititol in eyes
Laboratory findings in galactosemia?
elevated LFTS, low glucose, decrease coagulation factors, hyperchloremic metabolic acidosis
Two types of Neonatal Glycogen Storage Diseases?
Type 1 (Von Gierke)
Type II (Pompe)
What are organs are effected in Glucose 6-phosphatase deficiency?
(von Gierke)
Liver, Kidney GI
(you will see lactic acidosis)
What are organs are effected in lysosomal glucosidase deficiency?
(Pompe)
All organs, especially muscles and nerves
also see cardiomegaly and CHF
Laboratory findings urea cycle defects?
hyperammonia, respiratory alkalosis, normal glucose
What is most common urea cycle defect?
Ornithine carbamyl transferase
Laboratory abnormalities seen in OCT defiency?
Hyperammonemia, elevated urine orotic acid, decreased citrulline, decreased arginine.
All urea cycle defects have what laboratory abnormalities in common?
high glutamine and alanine.
Which urea cycle defect presents with spastic diplegia?
arginase deficiency
Why would you consider lactulose diet in urea cycle defect?
intestinal bacteria changes lactulose to lactic acid and low ph inhibits absoprtion of ammonia
Treatment of urea cycle defects and hyperammonemia
goal to remove nitrogen via medications
sodium benzoate, sodium phenylacetate
these meds create pathways to excrete nitrogen precursors
In urea cycle disorders supplent with what amino acid?
Arginine
(with lone exception of arginase deficiency) as arginine will become essential amino acid in these disorders
How do organic acidemias present? How does that differ than urea cycle defects?
ogranic acidimeas:
hypoglycemia, severe acidosis, ketosis
urea cycle
normal or slightly increased glycemia, mild acidosis (lactate), absent ketonuria
What are symptoms of Galctosemia Type II (galactokinase deficiency)
bilateral cataracts, developmental disability, pseudotumor cerebri
How do sodium benzoate and phenylbutarate work?
combine with glycine and glutamate respectively which leads to excretion of amino acids (involved in urea cycle) and allows for nitrogen excretion
when do you see elevated succinylacetone?
seen in transient tyrosinemia
or Hereditary Tyrosenimia type 1
what causes PKU
defect in enzyme phenylane hydroxylase leading to accumulation of phenylanaline derivatives.
Signs of PKU
delayed milestones, microcephaly, hypopigemntation, hyperactivity, seizrues, and musty order to skin
How does Nitisinone work?
works by inhibiting enzyme 4-hydroxyphenylpyruvate dioxygenase.
This enzyme is involved in degrading tyrosine to other toxic metabolites, which are responsible for disease-related symptoms.
Features of OTCD deficiency
elevated plasma alanine and glutamine levels
elevated urine orotic acid levels
plasma citrulline, arginine, and BUN levels decreased
The presence of lactic acidosis distinguishes these disorders from the organic acidemias?
Disorders of pyruvate metabolism
(carboxylase or dehydrogenase deficiency)
how do urea cycle defects present?
hyperammonia without acidosis
How/why is carnitine used?
fatty acid oxidation defects
not urea cycle disorders
how quickly do urea cycle defects present
24 hours
Where does metabolism of branch chain amino acids occur?
in the muscle
If there is hyperammonia and no acidosis, what is likely disorder?
probably urea cycle defect/ specific amino acid disorder
Important clues for fatty oxidation disorders in infancy?
elevated CPK and uric acid
with hypoketotic hypoglycemia
Other than diet restriction what can be helpful supplement in non-classical PKU?
5-Hydroxytryptophan
(bypasses block in serotonin synthesis)
serotonin requires tetrahydrobiopetrin
What is defect in branched chain amino acid disease (MSUD)?
BCKAD responsible for decarboxylation of respective alpha ketoacids, in MSUD their is defect in this and abnormal accumulation of alpha ketoacids, leading to symptoms
