Newborn screening for MCADD：对于MCADD新生儿筛查.pptVIP

Newborn screening for MCADD Dr Jean Kirk RHSC Edinburgh MCADD What is MCADD? How does it affect individuals who have it? What is known about long term effects? Feedback from newborn screening programmes in other countries Why is it being added to newborn screening in Scotland? What is MCADD? What is MCADD? Inherited disorder of one of the enzymes needed to break down fatty acids Medium Chain AcylCoA Dehydrogenase Deficiency What is MCADD? It is an autosomal recessive disorder, first identified in 1976 Carriers (parents) are not affected Two carriers have a 1 in 4 chance of having an affected child It is most common in people of North European origin Normal Fatty Acid Oxidation When is fatty acid breakdown activated? Just after a feed Fasted for a short time Fasted for a longer time, glucose and insulin levels beginning to fall Accelerated if unwell, vomiting, catabolic. Fatty acids become the energy source for the body brain Lack of insulin in diabetic ketoacidosis Fatty acid oxidation in MCADD MCAD deficiency Relative lack of ketones produced for the amount of fatty acids broken down Large quantities of toxic fatty acid intermediates produced that are encephalopathic Infant becomes drowsy, comatose and increasingly hypoglycaemic Rapid recovery when glucose given replenishes circulating glucose raises insulin levels. This switches off fatty acid oxidation stops toxic intermediate production Diagnosis in children/adultswho have not been newborn screened Investigations carried out in selected individuals only Older technology - urine organic acids More recent - tandem mass spectrometry Both detect compounds that are present in everyone in tiny amounts during normal fatty acid oxidation But are increased due to the block in the main fatty acid oxidation pathway in MCAD deficiency. Some markers are slightly increased even when person is well More markers are abnormally increased when unwell DNA mut