Pregnancy & Newborn Screening Developments

Medium Chain Acyl CoA Dehydrogenase Deficiency

(MCADD)

What is MCADD

• Medium Chain Acyl-CoA Dehydrogenase Deficiency

• Caused by the lack of an enzyme (‘catalyst’) required to convert stored fat to energy

• Affects 1 in 10,000 babies born in the UK

• In Scotland screening should identify 5 – 10 cases a year

What is MCADD

• Fatty acids are an important energy reserve (fuel) during periods of poor calorie intake, fasting or during infections

• Patients with MCADD have a deficiency of an enzyme necessary for the breakdown of medium chain fatty acids

• Medium chain fats accumulate and make toxic substances which cause serious symptoms.

Why screen for MCADD

• Early identification results in early treatment reducing risk of acute life threatening episodes

• Early detection of MCADD allows crisis/sudden death to be avoided

• Adherence to dietary management - normal life can be expected

Complications of MCADD

• Because fat fuels cannot be used, these patients quickly use up glucose and may develop hypoglycaemia

• High levels of partially broken down fatty acids and low blood glucose concentrations causes the patient to become drowsy, comatosed and eventually stop breathing

• Short term effects: seizures, cardiac arrest, coma, sudden death

• Long term effects: developmental and behavioural disabilities, failure to thrive, cerebral palsy and attention deficit disorder

• 1 in 4 infants die at 1st presentation before diagnosis made

Diagnosing MCADD

• Tandem Mass Spectrometry (TMS)

• Acyl carntine (C8) raised

• Diagnosis confirmed by repeat blood test at follow up visit

• DNA test for common mutations (Dundee laboratory)

• Carriers are not intentionally identified

How is MCADD managed?

• Scottish National Screening Laboratory notify Regional Metabolic Team (RMT) in Glasgow or Edinburgh

• RMT contacts family by telephone to give screening result and follow up plan

• RMT informs MCADD Designated Team (MDT)*• Provide MDT and/or GP, HV or midwife with MCADD resource pack• Arrange face-to-face consultation by member of MCADD

Designated Team and/or GP, HV or midwife as per local protocol• Arrange follow up visit with MCADD Designated Team within 24

hours or as soon as practically possible

*MDT may be same as the RMT for some NHS Boards

How is MCADD managed?

• Fasting should be avoided• Parents need to know how to manage a ‘metabolic crisis’• Regular ‘safe’ time between feeds/meals• Treat if vomiting/drowsy with glucose polymer feeds• Emergency – IV dextrose• Refer urgently to clinician who understands condition – metabolic

specialist• On going care shared between RMT and MDT

How is MCADD managed?

MCADD Resource Pack:

• MCADD is suspected leaflet• Contact details for MCADD Designated Team and the Regional

Team• A & E information • GP information

Genetic facts about MCADD

• A child that has MCADD has inherited two altered genes, one from each parent, both of whom are carriers

• It is thought that between 1 in 40 and 1 in 80 healthy people are carriers and do not have any symptoms

• MCADD gene found on chromosome 1

• Most common mutation,985A>G found in 85-90% of those with symptoms, but over 25 other variants found

Genetic facts about MCADD

• For each pregnancy where both parents are carriers, there is:

– 25% chance that the child will be born with MCADD

– 50% chance the child will be carrier of the MCADD gene

– 25% chance that the child will not be a carrier nor have the disease

Additional Management of MCADD

• Babies must complete a full immunisation programme

• Influenza vaccine is recommended annually

• Some children may require a supplement of a vitamin-like substance called carnitine to prevent carnitine deficiency

• Anaesthetic procedures require an infusion of dextrose before, during and following procedure

Family Issues

• Families will require genetic counselling

• Older siblings born before newborn screening started will need to be tested – arranged by metabolic clinician

• Next child: early testing as well as routine testing