aTreatment must also include management of airway, breathing, circulation, life-threatening organ failure, and intercurrent illness including sepsis, which is associated with galactosemi
Trang 1aTreatment 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