Pediatric emergency medicine trisk 612

ORGANIC ACIDEMIAS
Goals of Treatment
Goals of treatment specific to organic acidemias are to decrease organic acid production (by preventing
catabolism), enhance elimination of organic acids, and treat precipitating causes of decompensation, such
as infection.


TABLE 95.8
LABORATORY ABNORMALITIES, EMERGENT TREATMENT OF KNOWN IEMS


IEM category

Laboratory abnormalities

Abnormalities to treat
emergently (see Table 95.7 for
specifics) a

Aminoacidopathies

Hypoglycemia
Metabolic acidosis
± Increased anion gap
± Elevated lactate
Elevated transaminases
Ketonuria
Neutropenia, anemia
thrombocytopenia
± Hypoglycemia
Metabolic acidosis

Increased anion gap
± Elevated lactate
± Hyperammonemia
Elevated transaminases
Ketosis, ketonuria
Myoglobinuria
Hyperammonemia with
respiratory alkalosis
Metabolic acidosis
Hypoketotic hypoglycemia
± Elevated transaminases
± Hyperammonemia
± Elevated transaminases

Hypoglycemia
Acidosis

Hypoglycemia
Hyperchloremic metabolic
acidosis
Direct hyperbilirubinemia
Urinary-reducing substances

Acidosis

Hypoglycemia
Metabolic acidosis
± Increased anion gap
± Increased lactate, pyruvate
± Hyperammonemia

± Elevated transaminases

Acidosis

Organic acidemias

Urea cycle defects, disorders of
ammonia detoxification
Fatty acid oxidation defects

—
Disorders of carbohydrate
intolerance

Disorders of carbohydrate
production/utilization

Hyperuricemia
Ketonuria

Hypoglycemia
Acidosis
Hyperammonemia

Hyperammonemia
Hypoglycemia
Acidosis

Hypoglycemia

Hypoglycemia


a Treatment

must also include management of airway, breathing, circulation, life-threatening organ failure, and intercurrent illness including
sepsis, which is associated with galactosemia, congenital adrenal hyperplasia, and certain organic acidemias and glycogen storage disorders.
IEM, inborn error of metabolism.

Current Understanding
Organic acids are intermediary products of protein, fat, and carbohydrate metabolism. Their accumulation
results in metabolic acidosis, which is often very severe and usually associated with elevated anion gap.
Hypoglycemia is common because metabolic stress increases metabolic demand, which induces
degradation of glucose, and because toxic accumulations of organic acids inhibit gluconeogenesis.
Increased metabolism of fatty acids results in ketosis in certain organic acidemias, while others are
characterized by hypoketotic hypoglycemia. Hyperammonemia results from inhibition of the urea cycle
by organic acids. Organic acids also cause bone marrow toxicity that inhibits leukocyte and platelet
maturation, resulting in neutropenia and thrombocytopenia. Organic acidemias most likely to be
associated with acute decompensation are glutaric acidemia type I, holocarboxylase synthetase
deficiency, biotinidase deficiency, HMG-CoA lyase deficiency, maple syrup urine disease,
methylmalonic acidemia, and propionic acidemia.

Clinical Considerations
Assessment
Neonatal onset forms of organic acidemias usually present within the first week with life-threatening
metabolic decompensation. Clinical features include lethargy and/or encephalopathy progressing to
obtundation, feeding problems, vomiting, hepatomegaly, metabolic acidosis, hyperammonemia, and
neutropenia. Several of the organic acidemias result in a characteristic urine or body odor ( Table 95.2 ).
Infantile, late-onset forms tend to have a more insidious presentation with failure to thrive, seizures,
spasticity, hypotonia, and developmental delay. Affected individuals may have episodic metabolic

decompensation with rapid progression to coma, particularly with physiologic stressors. Many of the
clinical features can be prevented by initiation of disease-specific formula free of offending metabolites,
and/or disease-specific vitamin therapy for vitamin-responsive disorders, as soon as the diagnosis is
made.
Evaluation of patients with organic acidemias should include assessment of vital signs, electrolytes,
glucose, calcium, ammonia, AST, ALT, alkaline phosphatase, PT, PTT, plasma amino acids, serum
carnitine, blood gas, lactate, CBC, differential, platelets, urine-specific gravity and ketones, urine organic
acids, and as clinically indicated, tests for infection. If considering a lumbar puncture, recognize that
patients may have cerebral edema due to toxic concentrations of organic acids and/or ammonia.
Management
All protein intake should be stopped for 48 to 72 hours in the acutely ill child, while maintaining enteral
or IV calories to prevent catabolism. To treat dehydration, normal saline bolus(es), 10 mL/kg for neonates
and 20 mL/kg for infants and children should be administered. If the patient is hypoglycemic, dextrose
should be administered separately as a bolus of 0.25 to 1 g/kg; D10 is given for neonates, and D10 or D25
for infants and children. Ringer lactate should not be used. After administration of bolus fluid, D10 in ½
normal saline should be continued at 1 to 1.5 times maintenance. Because of the potential for severe
metabolic acidosis in these patients due to accumulation of organic acids, treatment of acidosis needs to
be more aggressive than with many other types of IEMs. Treatment of acidosis and hypoglycemia usually
corrects hyperammonemia. Hemodialysis is indicated to hasten clearance of metabolic toxins in the
obtunded or comatose patient and to correct persistent metabolic acidosis, hyperammonemia, and/or
severe electrolyte abnormalities. L -carnitine (25 to 50 mg/kg over 2 to 3 minutes or as an infusion added
to the maintenance fluid, followed by 25 to 50 mg/kg over 24 hours, maximum 3 g/day) may benefit
some patients with an organic acidemia but only in consultation with an IEM specialist. Glycine (150 to