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Emergency And Acute Medicine – Inborn Errors Of Metabolism
Basics
Description Inborn errors of metabolism are inherited defects in metabolic pathways that lead to abnormal accumulation or deficiency of metabolites. More than 400 disorders are described, most presenting in infancy or childhood with variable and often nonspecific findings. Incidence ranges from 1:10,000 to 1:200,000 births. Major categories include amino acid disorders, urea cycle defects, organic acidemias, fatty acid oxidation defects, mitochondrial disorders, carbohydrate disorders, lysosomal storage diseases, peroxisomal disorders, and disorders of protein glycosylation. Pathophysiology relates directly to enzymatic or transport defects within metabolic pathways.
Etiology Genetic deficiency of enzymes or membrane transport systems involved in intermediary metabolism.
Diagnosis
Signs and symptoms Presentation may be acute and catastrophic or chronic and indolent. Neonates may initially be asymptomatic or present with hypothermia (mitochondrial defects), hypotonia or hypertonia (peroxisomal disorders), apnea (urea cycle defects, organic acidemias), seizures, vomiting, poor feeding, jaundice, hypoglycemia, dysmorphic features, or coma. Older untreated children may present with failure to thrive, dehydration, recurrent vomiting or diarrhea, food intolerance, lethargy, ataxia, seizures, or developmental delay.
History Review newborn screening results, dietary history, family history, consanguinity, and intercurrent illness.
Physical exam May reveal abnormal odor, altered mental status, tachypnea, dysmorphic facies, cataracts, cardiomyopathy, hepatosplenomegaly, dermatitis, or jaundice.
Essential workup Consider in any child with unexplained neurologic deterioration, persistent vomiting, metabolic acidosis, hypoglycemia, shock unresponsive to resuscitation, or failure to thrive.
Diagnosis tests and interpretation
Lab Bedside glucose, electrolytes, BUN/creatinine, CBC, calcium, liver function tests, bilirubin, coagulation studies, blood gas, lactate, pyruvate, uric acid, urinalysis, ammonia, serum amino acids, urine organic acids, and cultures as indicated.
Imaging CT head for altered mental status; chest radiograph as indicated.
Procedures Lumbar puncture when infection is a concern.
Differential diagnosis Sepsis, meningitis, encephalitis, dehydration, toxic ingestion, nonaccidental trauma, Reye syndrome, hepatic encephalopathy, endocrine disorders, renal failure, renal tubular acidosis, CNS mass lesions.
Treatment
Prehospital Prioritize ABCs and bedside glucose. Start IV glucose immediately; do not delay for fluids unless in shock. Avoid lactated Ringer solution. Keep patient NPO.
Initial stabilization Administer glucose (after Accu-Chek and thiamine when appropriate) and naloxone for altered mental status.
Emergency department management Secure airway, breathing, and circulation. Use normal saline for fluid boluses and avoid hypotonic fluids and lactated Ringer. Initiate IV glucose at 8–10 mg/kg/min (D10 at 1.5× maintenance) to prevent catabolism. Treat severe hypoglycemia with D25 bolus. Correct dehydration and acid–base abnormalities; consider bicarbonate only if pH <7.0. initiate dialysis for refractory severe acidosis or hyperammonemia. stop all oral intake initially. treat hyperammonemia urgently with ammonia-scavenging agents (arginine, sodium benzoate, phenylacetate, phenylbutyrate) in consultation a metabolic specialist. identify and precipitating infections.< />pan>
Medication D25 2–4 mL/kg IV for hypoglycemia, sodium bicarbonate 1–2 mEq/kg IV for severe acidosis, disease-specific therapies such as levocarnitine or pyridoxine as indicated.
First line IV glucose infusion with normal saline as needed for shock.
Second line Bicarbonate therapy for pH <7.0 and hemodialysis when indicated.< />pan>
Follow-up and disposition
Admission criteria All infants and children with suspected inborn errors of metabolism, significant ketosis, inability to tolerate oral intake, altered mental status, severe or persistent acidosis, refractory hypoglycemia, or hyperammonemia; ICU care for severe presentations. Transfer to a specialized pediatric center is often required.
Discharge criteria Normal mental status, adequate hydration, reassuring laboratory results, no significant intercurrent illness, and close follow-up arranged.
Follow-up recommendations Ongoing care with a metabolic disease specialist and primary care physician.
Pearls and pitfalls Always consider metabolic disease in unexplained pediatric decompensation. Do not delay glucose infusion. Avoid lactated Ringer solution. Use bicarbonate cautiously and only for severe acidosis. Early dialysis can be lifesaving in hyperammonemia.
Basics
Description Inborn errors of metabolism are inherited defects in metabolic pathways that lead to abnormal accumulation or deficiency of metabolites. More than 400 disorders are described, most presenting in infancy or childhood with variable and often nonspecific findings. Incidence ranges from 1:10,000 to 1:200,000 births. Major categories include amino acid disorders, urea cycle defects, organic acidemias, fatty acid oxidation defects, mitochondrial disorders, carbohydrate disorders, lysosomal storage diseases, peroxisomal disorders, and disorders of protein glycosylation. Pathophysiology relates directly to enzymatic or transport defects within metabolic pathways.
Etiology Genetic deficiency of enzymes or membrane transport systems involved in intermediary metabolism.
Diagnosis
Signs and symptoms Presentation may be acute and catastrophic or chronic and indolent. Neonates may initially be asymptomatic or present with hypothermia (mitochondrial defects), hypotonia or hypertonia (peroxisomal disorders), apnea (urea cycle defects, organic acidemias), seizures, vomiting, poor feeding, jaundice, hypoglycemia, dysmorphic features, or coma. Older untreated children may present with failure to thrive, dehydration, recurrent vomiting or diarrhea, food intolerance, lethargy, ataxia, seizures, or developmental delay.
History Review newborn screening results, dietary history, family history, consanguinity, and intercurrent illness.
Physical exam May reveal abnormal odor, altered mental status, tachypnea, dysmorphic facies, cataracts, cardiomyopathy, hepatosplenomegaly, dermatitis, or jaundice.
Essential workup Consider in any child with unexplained neurologic deterioration, persistent vomiting, metabolic acidosis, hypoglycemia, shock unresponsive to resuscitation, or failure to thrive.
Diagnosis tests and interpretation
Lab Bedside glucose, electrolytes, BUN/creatinine, CBC, calcium, liver function tests, bilirubin, coagulation studies, blood gas, lactate, pyruvate, uric acid, urinalysis, ammonia, serum amino acids, urine organic acids, and cultures as indicated.
Imaging CT head for altered mental status; chest radiograph as indicated.
Procedures Lumbar puncture when infection is a concern.
Differential diagnosis Sepsis, meningitis, encephalitis, dehydration, toxic ingestion, nonaccidental trauma, Reye syndrome, hepatic encephalopathy, endocrine disorders, renal failure, renal tubular acidosis, CNS mass lesions.
Treatment
Prehospital Prioritize ABCs and bedside glucose. Start IV glucose immediately; do not delay for fluids unless in shock. Avoid lactated Ringer solution. Keep patient NPO.
Initial stabilization Administer glucose (after Accu-Chek and thiamine when appropriate) and naloxone for altered mental status.
Emergency department management Secure airway, breathing, and circulation. Use normal saline for fluid boluses and avoid hypotonic fluids and lactated Ringer. Initiate IV glucose at 8–10 mg/kg/min (D10 at 1.5× maintenance) to prevent catabolism. Treat severe hypoglycemia with D25 bolus. Correct dehydration and acid–base abnormalities; consider bicarbonate only if pH <7.0. initiate dialysis for refractory severe acidosis or hyperammonemia. stop all oral intake initially. treat hyperammonemia urgently with ammonia-scavenging agents (arginine, sodium benzoate, phenylacetate, phenylbutyrate) in consultation a metabolic specialist. identify and precipitating infections.< />pan>
Medication D25 2–4 mL/kg IV for hypoglycemia, sodium bicarbonate 1–2 mEq/kg IV for severe acidosis, disease-specific therapies such as levocarnitine or pyridoxine as indicated.
First line IV glucose infusion with normal saline as needed for shock.
Second line Bicarbonate therapy for pH <7.0 and hemodialysis when indicated.< />pan>
Follow-up and disposition
Admission criteria All infants and children with suspected inborn errors of metabolism, significant ketosis, inability to tolerate oral intake, altered mental status, severe or persistent acidosis, refractory hypoglycemia, or hyperammonemia; ICU care for severe presentations. Transfer to a specialized pediatric center is often required.
Discharge criteria Normal mental status, adequate hydration, reassuring laboratory results, no significant intercurrent illness, and close follow-up arranged.
Follow-up recommendations Ongoing care with a metabolic disease specialist and primary care physician.
Pearls and pitfalls Always consider metabolic disease in unexplained pediatric decompensation. Do not delay glucose infusion. Avoid lactated Ringer solution. Use bicarbonate cautiously and only for severe acidosis. Early dialysis can be lifesaving in hyperammonemia.
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