Inborn Errors of Metabolism

Selected Disorders

Screening Facts

• Different screening procedures are used in various states; all states assay for hypothyroidism
• Samples are acquired by heel lancing
• If the initial sample is sent before 24 hours of age, a second should be collected before two weeks of age to avoid false negatives
• Samples should be taken prior to administration of antibiotics or transfusion of blood or blood products [note that some newer assays are not affected by antibiotics, check locally].  Other factors that may affect the test results include heat and foreign substances such as powder from gloves, diet soda, etc.  TPN may cause false positive results in MSUD, PKU and homocyteinuria.
• Confirmation of positive newborn screening test results is always necessary.
• Some disorders (e.g., galactosemia and MSUD) may become symptomatic before results of the newborn screening are back and may warrant testing when clinically suspected
• Infants that might not get tested (those born prematurely, those who have received blood transfusions, those born out of state or country, those who underwent improper testing) should be repeated

Approach to Diagnosis

• Inborn errors of metabolism causing clinical manifestations in the neonatal period are usually severe and are often lethal if proper therapy is not promptly initiated.  A history of consanguinity and/or death in the neonatal period in the immediate family should increase suspicion of this diagnosis.  Inborn errors of metabolism of a geiven pedigree run true to type although symptoms may vary among siblings.
• These infants are usually normal at birth.  Signs and symptoms such as lethargy, poor feeding, convulsions, and vomiting may develop as early as a few hours after birth.  These clinical findings are usually nonspecific and similar to those seen in infants with generalized infections.  In contrast, other genetic disorders or perinatal insults usually cause abnormalities from the time of birth.  Occasionally vomiting may be severe enough to suggest pyloric stenosis.  Lethargy, poor feeding, convulsions, and coma may also be seen in infants with hypoglycemia or hypocalcemia.  Response to intravenous injection of glucose or calcium usually establishes these diagnoses
• Hepatomegaly is also a common finding in a variety of inborn errors of metabolism
• A physician caring for a sick infant should smell the patient and his or her excretions

• Measuring serum concentrations of ammonia, bicarbonate, and pH is helpful.  Elevation of blood ammonia is usually due to defects in urea cycle enzymes.  These infants will have normal serum pH and bicarbonate.  Elevation of serum ammonia has also been observed in some infants with certain organic acidemias but these infants would have a low blood pH.
• Even if death is inevitable, diagnosis should be made for genetic counseling of the family

Children

• An inborn error of metabolism should be considered in any child with one or more of the following manifestations: 1) unexplained mental retardation, developmental delay, motor deficits or convulsions; 2) unusual odors, particularly during an acute illness; 3) intermittent episodes of unexplained acidosis, mental deterioration, or coma; 4) hepatomegaly; or 5) renal stones.
• There may be an episodic or intermittent pattern of symptoms.  The episodes are usually triggered by a stress or a nonspecific insult such as infection.  The child may die during one of these acute attacks

Sources

Champe, Harvey.  Lippincott's Illustrated Reviews: Biochemistry.  J.B. Lippincott Co., Philadelphia, 1994.

Committee on Genetics.  "Newborn Screening Fact Sheets".  Pediatrics 98(3), September 1996.

Stoddard, Farrell.  State-to-State variations in newborn screening policies.  Archives of Pediatric and Adolescent Medicine 151, June 1997

Acknowledgment