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155 Copyright © 2004 The Regents of the University of California : Inborn Errors of Metabolism infancy, not with a specific laboratory abnormality, but with organomegaly, facial Peroxisomal disorders, Zellweger syndrome and neonatal adrenoleukodystrophy) result from failure of the peroxisomal enzymes. They may present with features similar to the lysosomal storage disorders. Commger syndrome include large fontanel, organomegaly, Down-like faciesdisordered steroidogenesishyperplasia or Smith-Lemli-Opitz), disorders of metal metabolism (Menkes syndrome, neonatal hemochromatosis). T is more prevalent in slightly premature infants receiving mechanical usually within the first 24 hours of life. The ammonia level may be markedly elevated and dialysis may be evidence of impaired ammonia metabolism. CLINICAL FINDINGS -History of consanguinity, mental retardation, or SIDS; symptom onset with institution of feedings or formula change; history ofemesis, poor feeding, rashes, seizurhepatosplenomegaly, ambiguous genitalia, jaundice, dysmorphic or coarse facial or pigmentary retinopathy), intracranial hemorrhage, unusual odors. metabolic acidosis with increased anion gap, primary respiratory alkalosis, hyperammonemia, hypoglycemiahyperbilirubinemia, lactic acidosis, high lacton tests including PT and PTT, neutropenia and thrombocytopenia. non-metabolic causes of symptoms such as infectionconsult from Genetic/Metabolic Service • Blooduric acid, ammonia. Other studies may be indicated as described in algorithm • Urinegalactosemia, fructose intolerance, tyrosinemia and others), ferric chloride reaction acids). Amino and organic acids as described in algorithm below. • CSF: glycine (for nonketotic hyperglycinemia) are adapted from Burton BK: Inborn errors of metabolism in infancy: A guide to diagnosis. Pediatrics 102:E69, 1998. metabolic acidosis (Figure gorithm is in Rudolph’s Pediatrics, 20Not all inborn errors of metabolism will present with acidosis, hyperammonemia, Inborn Errors of Metabolism , seizures, obtundation) may be the predominant feature in several IEMs (, nonketotic hyperglycinemia, molybdenum cofactor deficiency, peroxisomal disorders). Figure 1. Flow chart for differentiarginosuccinic acid; CPS, carbamyl phosphate synthetase; OTC, ornithine transcarbamylase; PC, pyruvate carboxylase). Chart is adapted from Burton BK: FURTHER MANAGEMENT Although treatment differs for each specific disorder, each should be managed by considering the potential disease category and by following the following steps, along with consultation with a metabolic specialist-Hydration/nutrition/acid-base management: eliminate protein, galactose and fructose. mg/kg/min (even if insulin is required to keep the blood glucose level normal). Give IV lipids only after ruling Withhold all protein for 48 to 72 hours, while the patient is acutely ill, and until an aminoacidopathy, organic acidurspecial enteral formulas and parenteral amino acid solutions are available for many disorders. Treat significant Symptoms after age 24h Acidosis ORGANIC ACIDEMIAS Noacidosis DEFECTS PLASMA AMINO ACIDS AbsentCitrulline Urine Orotic Acid Low Citrulline moderatelyelevated, ASA present Arginosuccinic Citrulline markedly no ASA Citrullinemia NEONATAL HYPERAMMONEMIA Symptoms in 1 t 24h Hyperammonemia of Newborn Full Ter m INBORN ERROR OF METABOLISM , organic acidemiaor PC deficiency) Inborn Errors of Metabolism -Elimination of toxic metabolites: Treatment of severity of neurological impairment in induration of the hyperammonemic coma. For severe hyperammonemiaindicated. Dialysis may also be indicated for intractable anion gap metabolic acidosis. Figure 2. Flowchart for evaluation of metabolic acidosis in the young infant.se; GSD, glycogen storage disease; L:P ratio, lactate to Chart is adapted from Burton BK: Pediatrics 102: E69, 1998. -Treatment of coexisting/precipitating factors , infection, thrombocytopenia). : Certain enzyme deficiencies are vitamin-responsive, including: The vitamin-responsive form of propionic acidemia, beta-methylcrotonyl biotin (5 mg daily, oral or parenteral). Vitamin-responsive methylmalonic acidemia: Vitamin B12 (1 mg daily, IM). Vitamin-responsive maple syrup urine disease: thiamine (50 mg daily, oral). o hypoglycemia PYRUVATE DEHYDROGENASE DEFICIENCY; PYRUVATE CARBOXYLASE DEFICIENCY N ormal or low pyruvate;elevated L:P ratio RESPIRATORY CHAIN DEFECTS; PYRUVATECARBOXYLASE DEFICIENCY ormalorganic acids METHYLMALONIC ACIDEMIA;PROPIONIC ACIDEMIA; MULTIPLE CARBOXYLASE DEFICIENCY; OTHERS Dicarboxylic aciduria TTY ACIDOXIDATION DEFECTS Abnormalorganic acids Abnormalorganic acids ORGANICACIDEMIA METABOLIC ACIDOSIS WITH INCREASED ANION GAP ormal lactate Elevated lactate GSD TYPE 1; FRUCTOSE 1,6DP DEFICIENCY; PEP CARBOXYKINASE DEFICIENCY Elevated pyruvate;normal L:P ratio Hypoglycemia Inborn Errors of Metabolism It is important to make a specific diagnosisinformation that might affect future is not permitted, request consent for pre-mortem or immediately post-mortem specimens. should be centrifuged and the plasma should be frozen. should be refrigerated. sterile skin biopsymed within 1-2 hours inhibit cell growth. Place skin sample in sterile saline at room temperature and send to Other tissue samples (, liver, skeletal muscle, cardiac muscle, brain, kidney) may be If there are dysmorphic features, consider a full skeletal radiological series. At present, for most IEMs, prognosisoutcome is guarded, despite appropriate and aggressive therapy. It is likely that the outcomes will improve with (a) presymptomatic diagnosis (i.e.) identification of genes and other factors which impact on phenotype, response to treatment, and outcoto therapy.