Approach to Inborn Error of Metabolism in a Neonate

Objectives
To recognize IEM in a neonate with nonspecific signs and symptoms To make use of simple lab tests in the diagnosis of IEM To know the initial management of life threatening conditions associated with IEM

 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

 Mostly due to defect in or absence of an enzyme, cofactor or transport protein resulting a block 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

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, CNS hemorrhage, other congenital/acquired conditions

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

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

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 80100kcal/kg/day Eliminate protein acutely (24-48h) IV lipids maybe contraindicated in certain FAO defect

 Hemodialysis
Eg. Hyperammonemia

Vitamin treatment
Useful for several types of IEMs

Medication to treat hyperammonemia

Sodium phenylactate, sodium phenylbutyrate, sodium benzoate

 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

Methylmalonic acidemia

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

Bring home message

Early recognition of IEM and prompt management are essential to prevent death or neurodisability IEM should be considered in the differential diagnosis of any sick neonate along with common acquired causes such as sepsis, hypoxic-ischemic encephalopathy, ductdependant cardiac lesions, congenital adrenal hyperplasia and congenital infections

References
Paediatric Protocols for Malaysian Hospital, 3rd edition Gomella TL. Neonatology. Lange 6th edition, 2009. 510 534 Burton BK. Inborn Errors of Metabolism in Infancy: A Guide to Diagnosis. Pediatrics 1998;102;e69 Sharma S et al. Approach to Inborn Errors of Metabolism Presenting in the Neonate. AIIMSNICU protocols 2010