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 1 st 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