Term
| Newborn vulnerability to inborn errors of metabolism |
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Definition
1. Increased catabolism during first few weeks of life
2. Down regulation of metabolic function (liver enzymes)
3. Just came off 9 months of "life support" |
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Term
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Definition
1. Excess substrate (can go into alternate pathways) and low/no product
2. Vulnerability of newborns
3. Vulnerability of the brain (very metabolically active)
4. Many processes are involved (production of ATP and protein, toxin clearance, conversion, and degradation)
5. Toxic biomolecules |
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Term
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Definition
Ammonia
Glycine
Lactic acid
Organic acids - intermediates in AA breakdown
Galactose |
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Term
| Progression of symptoms of IEM |
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Definition
Patients are initially stable at birth and then problems can arise anywhere from 24 hours to a few weeks later
Initial symptoms include sleepiness, vomiting, lack of eating (similar to SEPSIS!)
Then progresses to coma, seizures, cerebral edema, respiratory distress, and immune suppression |
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Term
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Definition
Heart diseases
Seizures
Starvation
Liver disease
Valproate
TPN
Penicillins |
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Term
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Definition
UC is a pathway for nitrogen disposal
Ammonia --> urea (gets excreted) |
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Term
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Definition
Newborn period with hyperammonemia (neurotoxicity) and respiratory alkalosis
Hyperammonemia leads to vomiting, lethargy, and then coma/death within 48 hours |
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Term
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Definition
Hyperammonemia is crucial
Plasma AAs - increased glutamine, decreased arginine |
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Term
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Definition
Environmental factors can trigger UCD symptoms
Liver damage, drugs (valproic acid), too much protein |
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Term
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Definition
Focuses on reduction of nitrogen accumulation (dialysis if necessary)
Diet modification
Eventually will need liver transplant |
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Term
| Branched chain AA disorders |
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Definition
Leucine, isoleucine, and valine
Typical presentation: A few days after birth develop poor feeding, drowsiness, coma, cerebral edema, with bulging fontanelle, hypertonia, seizures, respiratory failure |
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Term
| Maple syrup urine disease |
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Definition
Branched chain AA disorder
Defect of branched chain keto-acid dehydrogenase (thiamine dependent)
Leads to accumulation of abnormal 2 oxo-acids in plasma, urine, CSF which leads to characteristic smell
Isoleucine gets tautomerized to alloisoleucine which is a diagnostic compound for this disease!
No/mild hyperammonemia because UC is mostly uninvolved |
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Term
| Characteristic abnormalities of MSUD on labs |
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Definition
Plasma AAs - show massive elevation of BCAAs
Disturbed ratio of BCAAs
Large ketones on urinalysis |
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Term
| Why is MSUD so dangerous? |
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Definition
| Elevated leucine is an emergency - must be removed with dialysis |
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Term
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Definition
Remove leucine with dialysis
Start high energy/low protein diet - restrict leucine, supplement thiamine |
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Term
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Definition
Episodic decompensations with high risk of sudden death from herniation
Pancreatitis
Epidermolysis
Long term disability that is inversely correlated with length of leucine elevation |
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Term
| Methylmalonic acidemia/Propionic acidemia |
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Definition
Toxic encephalopathy, hyperammonemia, hypoglycemia
Diagnosis confirmed with urine organic acid labs
Variability in presentation: can present in newborns or adolescents. Symptoms normally include poor feeding, respiratory distress, vomiting, seizures |
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Term
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Definition
Rehydration and promotion of anabolism
Dialysis for hyperammonemia
Special diet
Carnitine, biotin, and cobalamin supplementation
Metronidazole |
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Term
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Definition
Severe, recurrent decompensations
Severe neurologic outcome - basal ganglia particularly sensitive
Chronic renal failure
Cardiomyopathy
Pancreatitis
Epidermolysis |
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Term
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Definition
IVA leads to isovaleric acid accumulation (highly toxic)
Presentation is similar to MMA/PA - sweaty feet odor |
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Term
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Definition
Deficiency in phenylalanine hydroxylase (PAH) which converts Phe to Tyr
AR inheritance
1/16000
MR and autism
Dietary therapy is important
Mothers with PKU can give birth to children with MR, microcephaly, low birth weight |
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