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7/30/2019 Approach to Inborn Error of Metabolism in a Neonate
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Approach to Inborn Error of
Metabolism in a Neonate
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Objectives
To recognize IEM in a neonate with non-specific signs and symptoms
To make use of simple lab tests in thediagnosis of IEM
To know the initial management of lifethreatening conditions associated with IEM
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IEMs may account for as much as 20% of
disease among full term infants not known
to have been born at risk.
>1 in 500 live births
*IEM should be considered in any sick
newborn
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Mostly due to defect in or absence of anenzyme, cofactor or transport protein resulting ablock in a specific metabolic pathway
Generally single gene defects Involve all inheritance patterns, however, most
common is autosomal recessive
Common defects on a biochemical level
Transport defects Accumulation of substrate
Deficiency of product
Secondary inhibition
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Special consideration
Family history of mental retardation, syndromic baby,sudden infant death syndrome, known metabolic disease
Parental consanguinity
Onset of signs and symptoms after a period of good
health Introduction and progression of enteral feelings maybe
related to symptoms
Failure of usual therapies to alleviate symptoms or
inability to prove a suggested diagnosis eg. Sepsis, CNShemorrhage, other congenital/acquired conditions
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Signs and Symptoms
Variable; May be
Gradual
Sudden
Catastrophic
Seizures and abnormal muscle tone
Poor feeding difficulty, vomiting, diarrhea,
Tachypnea, dyspnea, tachycardia Odour
Dysmorphic features
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Initial investigations
Full blood count
Urinalysis
Blood gases
Serum electrolytes
Blood glucose
Plasma ammonia
Urine reducing substances
Urine ketones (if acidosis or hypoglycemia present)
Plasma and urine amino acids
Urine organic acids
Plasma lactate
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Management
Acute care Supportive care
Secure airway, respiration and circulation
Correction of acid-base balance, electrolyte abnormalities,
hydration status Antibiotic therapy
Nutritional measure Nil by mouth
Supply of sufficient glucose with caloric intake 80-100kcal/kg/day
Eliminate protein acutely (24-48h)
IV lipids maybe contraindicated in certain FAO defect
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Hemodialysis
Eg. Hyperammonemia
Vitamin treatment
Useful for several types of IEMs
Medication to treat hyperammonemia
Sodium phenylactate, sodium phenylbutyrate,
sodium benzoate
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Specific management depends on diagnosis Consult team
Diet modification and provision of deficient
substance Genetic counselling
Neonatal screening Tandem mass spectrometry
Highly sensitive, specificity is relatively low difficulties in interpretation of abnormal test results in
apparently healthy infants.
Expensive
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Methylmalonic acidemia
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Autosomal recessive
A type of organic acid disorder
Commonly present in neonatal period
Nearly indistinguishable with pronionic acidemia and
isovaleric acidemia Accumulation of methylmalonic acid in body
Features metabolic acidosis with anion gap
Hyperammonemia
Encephalopathy with seizures Hyperglycinemia, hypoglycemia
Neutropenia, thrombocytopenia
ketonuria
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Bring home message
Early recognition of IEM and promptmanagement are essential to prevent death or
neurodisability IEM should be considered in the differential
diagnosis of any sick neonate along withcommon acquired causes such as sepsis,
hypoxic-ischemic encephalopathy, duct-dependant cardiac lesions, congenital adrenalhyperplasia and congenital infections
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References
Paediatric Protocols for Malaysian Hospital, 3rdedition
Gomella TL. Neonatology. Lange 6th edition,
2009. 510
534 Burton BK. Inborn Errors of Metabolism in
Infancy: A Guide to Diagnosis. Pediatrics1998;102;e69
Sharma S et al. Approach to Inborn Errors ofMetabolism Presenting in the Neonate. AIIMS-NICU protocols 2010