Inborn Error of metabolism - WordPress.com · •Inborn errors of metabolism (IEM) are a...
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Inborn Error of metabolism
Dr. Dafalla A. Babiker
Dr. Mohamed Waheed
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definition
• Inborn errors of metabolism (IEM) are a
heterogeneous group of diseases that may or
may not be detected by newborn screening.
• Early recognition of these disorders is
important to institute therapy and to prevent
neurologic damage.
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• IEM may present with an acute crisis—often with encephalopathy the neonatal period—or with a more indolent, chronic course. In addition to the common presenting symptoms of IEM (listed below), a family history of mental retardation, neonatal death in siblings, or parental consanguinity may increase the suspicion of IEM.
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• Findings suggestive of an acute IEM crisis (often confused with sepsis)
• poor feeding
• persistent vomiting
• lethargy
• convulsions resistant to IV glucose or calcium
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• hypotonia or spasticity
• tachypnea/Kussmaul breathing/apnea
• failure to thrive
• coma
• lack of improvement to any of the above with standard therapy
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• Findings suggestive of a chronic IEM course
• developmental delay (especially regression)
• seizures resistant to anticonvulsant therapy
• movement disorder
• peripheral muscle weakness
• cardiomyopathy
• hepatosplenomegaly
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• hypoglycemia • renal failure
• cataracts
• retinal abnormalities
• macrocephaly
• dysmorphic features
• unusual body odors
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Workup for suspected IEM
• CBC, differential, and platelets
• serum electrolytes
• arterial blood gas
• serum glucose
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workup
• plasma ammonia level
• urine for reducing substances
• urine for organic acids
• urine and blood for amino acids
• urine for ketones if the neonate is hypoglycemic or acidotic
• liver function tests if the child has encephalopathy
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Hypoglycemia
• Associated acidosis suggests organic acidemias
• Associated hepatomegaly or liver failure suggest glycogen storage disorders, galactosemia, or tyrosinemia
• Normal anion gaps and lactic acid levels suggest hyperinsulinemia or fatty acid oxidation defects
• Associated hyponatremia and hypotension suggest adrenal insufficiency
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Emergency treatment
• Remove accumulating metabolites with hemodialysis
• Stop all protein ingestion
• Glucose if patient is hypoglycemic
• Arginine infusion if you suspect a urea cycle defect
• B12 and biotin administration if you suspect an organic acidemia
• Send appropriate labs
• Consultation with geneticist or metabolic specialist
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Dying patient
• If the patient is dying, it is important to obtain appropriate materials for diagnosis. Urine and separated plasma should be frozen, a tissue sample must be obtained and placed in special medium, and a needle biopsy of the liver should be obtained.
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IEM categories with examples
Defects in amino acid metabolism
• Phenylketonuria
• Homocystinuria
• Alcaptonuria
• Hereditary tyrosinemia
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Defects in carbohydrate metabolism
• Galactosemia
• Glycogen storage diseases (von Gierke, Pompe)
• Defects in fatty acid oxidation
• Short/medium/long-chain acyl-CoA dehydrogenase deficiency
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Urea cycle defects
• Ornithine transcarbamylase deficiency
• Carbamyl phosphate synthetase deficiency
Lysosomal Storage Diseases
• Gangliosidoses (Tay-Sachs, Gaucher, Nieman-Pick)
• Mucopolysacharidoses (Hurler, Hunter)
Defects in heme pigment biosynthesis
• Acute intermittent porphyria
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Disorders of metal metabolism
• Wilson’s disease
• Hemochromatosis
• Mitochondrial disorders
• MERRF
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Interesting associations between body/urine odor and IEM
• Musty/mousy = phenylketonuria
• Boiled cabbage = tyrosinemia, hypermethioninemia
• Maple syrup = maple syrup urine disease
• Rotting fish = trimethylaminuria
• Sweaty feet = isovaleric academia, glutaric academia (type II)