Homocystinuria, Newborn Bloodspot Screening


 Homocystinuria is an autosomal recessive condition resulting from the accumulation in blood of the essential amino acid methionine and one of its metabolic products homocysteine.  Homocysteine accumulates due to a deficiency of the enzyme cystathionine b -synthase.  Homocysteine is toxic to the lining of the blood vessels and predisposes the individual to thrombus formation and blood clots and a number of other complications including osteoporosis (thinning of the bones) and eye complication.  The treatment is similar to that for PKU; for those individuals who adhere to the diet for life, the risk of developing any of the complications is greatly reduced. Approximately one in every 65,000 infants born in Ireland may have the condition or one case every year.

The screening programme detects high blood levels of methionine.  This is one of the more difficult conditions to screen for as methionine is low in most baby foods, particularly in breast milk.  The screening programme may not detect approximately one in every five infants born with this condition.  There are a variety of reasons why this may occur. These include:

  • breast fed infants as there may be an inadequate intake of methionine in the feed to enable detection;
  • a milder vitamin B6 responsive form of the disorder.

Consequently all infants who present clinically in later life with signs and symptoms suggestive of homocystinuria, such as dislocation of lenses, osteoporosis and inappropriate tall stature should have the disorder excluded formally by measuring plasma levels of total homocysteine.

 Action following detection of raised result

Initially the bloodspot methionine level may be only slightly raised; the NNBSL may request a further newborn screening sample.  If the bloodspot methionine level is raised, HCU is suspected; the following clinical procedure is implemented:

1.      The Clinical Liaison Officer (NNBSL) will:

  • Contact the Maternity Unit in which the baby was born.  Clear verbal instructions are given to the Maternity Unit Contact to include the child’s demographic details, the condition suspected and the arrangements for further examination locally.  The Maternity Unit Contact is asked to give the mobile telephone number of the Director of the NNBSL to the parents; the parents are invited to contact the Director to obtain more information should they so wish.
  • Contact the Metabolic Laboratory to inform them to expect a sample for plasma LFTs,  methionine and total homocystine analysis
  • Inform the Registrar or Consultant Metabolic Paediatrician on duty of the possibility of a new case of HCU

2.      On admission to the local hospital, the child should be examined clinically and blood taken for plasma bilirubin and LFTs

  • Sent 2mL blood in lithium Heparin for quantitative amino acids analysis.  Separate the plasma and deproteinise an aliquot immediately as follows: 1 vol 35% Sulphosalicylic Acid to 10 vol of plasma ie 20 or 50µL plus 200 or 500µL as appropriate.  Neat plasma is also required for total homocystine. Send the plasma samples immediately to the Metabolic Laboratory at Temple Street.
  • If the plasma methionine and total/free homocystine levels are raised, arrangements should be made to review the child in the metabolic outpatient clinic at the Children’s University Hospital, Temple Street, following consultation with the Consultant Metabolic Paediatrician on duty

Once the diagnosis has been confirmed the screening process is complete