Clinical approach the the child with a
suspected IEM:
Labs: First thought should be Infection vs. Metabolic
disorder. CBC, VBG (plasma pH and CO2), serum ammonia, electrolytes and glucose,
plasma amino acids, urine organic acids, plasma lactate and pyruvate, plasma
total and free carnitine (if FAO defect is suspected, and then further workup
would include sending for plasma acylcarnitine profile to look for elevation).
Urine should be fresh frozen. In the setting of refusal to feed and lethargy,
the workup for metabolic disease should be conducted concurrently with other
investigations (infectious, etc), because delay in diagnosing an inborn error of
metabolism can lead to substantial neurologic damage that may be permanent.
- Etiology:
- nearly all are recessive
- most are autosomal
- Variable, non-specific presentations:
- sepsis-like clinical appearance
- vomiting and/or FTT, poor feeding
- episodic changes in consciousness; lethargy
- seizures
- metabolic acidosis
- mental retardation / developmental delay
- coma
- 'the deterioriation of a previously well neonate suggests an
intoxication type of metabolic disorder. These problems typically present
with poor suck and feeding followed by increasing lethargy and coma. The
most common ones are the organic acidemias, maple syrup urine disease, urea
cycle defects, and nonketotic hyperglycinemia
Categories
- Urea cycle defects
- No acidosis, High ammonia
- the profoundly ill neonate with neurologic symptoms, or profound hypotonia
and coma in a previously well infant
- Aminoacidopathies
- No acidosis, normal ammonia
- ie PKU, MSUD, Hereditary tyrosinemia, Nonketotic hyperglycinemia
- may present similarly to organic acidemias,
but are a very heterogeneous group
- Organic acidemias
- Metabolic acidosis (ammonia may be high or normal)
- the most common are Proprionic acidemia, Methylmalonic acidemia,
isovaleric acidemia. Also MSUD
- Fatty acid oxidation defects:
- very low glucose, nml/slightly elevated ammonia, gap acidosis, no ketones,
tachypnea
- lysosomal storage diseases
- (incl lipidoses, glycoproteinoses, mucopolysaccharidoses)
- do not present with acidosis in the newborn
- accumulation of glycoproteins, glycolipids, or glycosaminoglycans within
lysosomes in various tissues.
- present later in life with organomegaly,
facial coarseness, and neurodegeneration
- peroxisomal disorders
- present with dysmorphia and profound hypotonia; send for plasma long chain
fatty acids (most common adrenoleukodystrophy. also Zellweger)
- carbohydrate metabolism disorders
Most are Autosomal Recessive (except OTC
deficiency: X-linked)
(Chief Resident Weekly Pearl 9/04)
Emergency Department Care: Initial ED treatment does not
require knowledge of the specific metabolic disease or even disease category
In any critically ill child, airway, breathing, and circulation must be
established first. Consider antibiotics in any child who may be septic.
Initial treatment of IEMs is aimed at correcting metabolic abnormalities.
Even the apparently stable patient with mild symptoms may deteriorate rapidly
with progression to death within hours. With appropriate therapy, patients may
completely recover without sequelae. Start empirical treatment for a potential
IEM as soon as the diagnosis is considered.
- Eliminate potentially harmful protein or sugars.
All oral intake should be stopped.
- Treat hypoglycemia and prevent
catabolism.
Restrict
protein intake
- Correct hypoglycemia, if present, by
IV dextrose bolus, 25%, 1-2 mg/kg
and followed by continuous
administration of dextrose.
- For all patients in whom an IEM cannot be ruled out, give
dextrose 10-15% IV at a rate high
enough to prevent catabolism (8-10 mg/kg/min). (D10 = 10 g glucose/100mL)
- Dextrose will improve most conditions.
- Add insulin, 0.2-0.3 IU/kg, as
needed to maintain normoglycemia.
- Add electrolytes at
maintenance concentrations with appropriate adjustments to correct
electrolyte disturbances if present.
- Treat acute acidosis. The
pH and dose at which bicarbonate
should be administered are controversial; pH <7.0-7.2, dose
0.35-0.5 mEq/kg/h up to 1-2 mEq/kg/h.
When patients are symptomatic or severely hypokalemic,
potassium acetate is a useful
replacement fluid (1 mEq/kg/h). Rapid correction or overcorrection may
have paradoxical effects on the CNS. For intractable acidosis, consider
hemodialysis.
- Definitive treatment of IEM
requires removal of abnormal metabolites by restricting intake of the
offending substrate, by promoting renal excretion of toxic metabolites, or, in
severe cases, by dialysis (preferably hemodialysis).
- Significant hyperammonemia is life threatening and must be treated
immediately upon diagnosis.
- To reduce ammonia,
sodium phenylacetate and sodium
benzoate can be administered
to augment nitrogen
excretion.
- Arginine is an essential
amino acid in patients with some
urea cycle defects.
- For ammonia greater than 500-600
mcg/dL, hemodialysis should be initiated.
- If hemodialysis is not readily
available, peritoneal dialysis (<10% as effective as hemodialysis) or
double volume exchange transfusion (even less effective) can be performed
while arrangements are made to transport to a center where hemodialysis is
possible, as long as this does not delay transfer.
- Two to 3 days of therapy is usually necessary.
- L-carnitine may be administered
empirically in life-threatening situations associated with primary metabolic
acidosis or hyperammonemia.
- Administration of carnitine to patients with fatty acid oxidation
defects is controversial.
- Pyridoxine should be
given to neonates with seizures unresponsive to conventional
anticonvulsants.
http://www.emedicine.com/emerg/topic768.htm
Pediatrics, Inborn Errors of Metabolism
Last Updated: February 22, 2005