Metabolic Disorders Flashcards
General characteristics of inborn errors of metabolism
Infants generally normal at birth (protected by maternal circulation)
Congenital malformations are NOT typical (exceptions)
Usually autosomal recessive (single gene mutations)
CLINICAL VARIABILITY!!!!!
—>broad range of severity within disease
—>many show variability within a family
Many have CNS impairment associated
Ex of neurologic abnormalities
Hypotonia
Hypertonia
Seizures
Retardation
Growth failture ex
Abnormal growth…
Feeding intolerance presents as
Vomiting
Diarrhea
Metabolic derangement
Acidosis
Hyperammonemia
***these are the hallmark presentations of metabolic errors
Clinical effects of metabolic errors
All organ systems can be affected
Any combination of organs can be affected
Clinical variability is very important
Age of onset
Infancy = most severe and most typical
The later the onset…the less severe the disease will be
There is alot of variability with onset with each known mutation though…like in Gaucher Disease
Therefore…cannot predict onset with mutation!!
Methods of diagnosing
- Clinical pattern (phenotype)
—>specific pattern (fetal alcohol syndrome, only way to diagnose this) - Biochemical marker (by specific biochemical test)
—> substrate/analyate abnormality (PKU)
—>enzyme analysis (galactosemia)
—> histopathologic (mitochondria) - DNA-based diagnosis (known disease-associated mutation) (very long chain acyl-CoA dehydrogenase)
Typical symptoms of metabolism error (things you look for while sepsis test is underway…)
Unusual odor
Metabolic acidosis
CNS involvement
Hyperammonemia
Match these tests with the interpretation
- Capillary blood gas
- Serum bicarbonate
- Serum glucose
- Serum ammonia
- Serum lactate
- Urine reducing substrate
- Urine ketones
- Acidosis/alkalosis
- Acidosis/alkalosis
- Gluconeogenesis
- Urea cycle, liver disease
- Gluconeogenesis, energy metabolism (mitochondria)
- Carbohydrate metabolism
- Fatty acid metabolism/gluconeogenesis
What does an excess anion (organic acid or lactic acid) mean probably?
Build up of certain substrate due to malfunctioning enzyme
What test should be done to establish diagnosis and start of specific therapy…once blood test came back with metabolic errors characteristics?
Urine organic test
Isovaleric acidemia
Huge amounts of isovalerylglycine in urine
—> problem with isovalerylCoA dehydrongenase
(Leucine metabolic pathway
Build up with isovalerylCoA will cause an increase in isovalerylcarnitine and isovalerylglycine
Will be carnitine deficient - give supplement
Clinical features of IVA
- First 2 weeks after birth
Early: lethargy, feeding problems, foul odor (sweaty socks)
late: metabolic acidosis, coma, twitching
Lab findings of IVA
Metabolic acidosis with increased anion gap (+/- respiratory alkalosis)
Thrombocytopenia (deficiency of platelets)
Neurtopenia (low levels of neutrophils)
Pancytopenia (deficiency of RBCs, WBCs, and platelets)
Urine organic acids: —> isovalerylglycine —>isovaleric acid —> isovalerylcarnitine Secondary = carnitine deficiency (increased acyl:free carnitine ratio)
Treatment during IVA (acute phase)
Discontinue all protein products
High glucose infusion
IV carnitine
Intubations of profound acidosis (rare)
Bicarbonate administration if necessary
IVA treatment during recovery period
Continue high caloric input (nonprotein) to prevent catabolism
Slowly introduce protein
I-valex formula: leucine free, contains glycine - pt will have enough to grow
Enteral carnitine
Lab findings in recovery period of IVA
Normal ammonia, pH, glucose, ketons, mild neutropenia, thrombocytopenia
Significant elevation in urine of isovalerylglycine - normal for patient
—>increased acyl:free carnitine in urine
—> normal plasma leucine
Bone marrow suppression
Treatment of inborn errors of metabolism
Avoid the offending agent (Decrease amount of substrate for deficient enzyme)
Supply missing cofactor or enzymes
Gene therapy has not been successful
