approach to inborn error of metabolism in a neonate

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

approach to inborn error of metabolism in a neonate

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