Newborn screening in England and Northem Ireland includes screening for medium chain acylcoenzyme A dehydrogenase (MCAD) deficiency within the entire newborn population. M CAD deficiency is the most common inherited disorder of mitochondrial fatty acid oxidation in people from northern Europe. This autosomal recessive metabolic disease affects about one in 10000 people in the United Kingdom. Homozygosity for this mutation has not been found in black or Asian ethnic groups that have been screened in England, which suggests that MCAD deficiency caused by the 985A>G mutation is a disease of white ethnic origin.
Individuals with undiagnosed MCAD deficiency typically present clinically with failure of fatty acid oxidation after fasting and an inability to generate energy during periods of increased energy demand. With symptomatic hypoglycaemia through hepatic encephalopathy (similar to that seen in Reye’s syndrome) to sudden unexpected infant death, which may be classified as sudden infant death syndrome. Most cases present before 2 years of age (mean age 13 months), although a variable spectrum of disease is increasingly recognised, with both neonatal and adult presentation being reported
About a third of affected individuals will remain asymptomatic throughout life but may be at risk of metabolic decompensation in periods of critical energy supply-for example, during infection or prolonged fasting.
About 25% of patients with undiagnosed MCAD deficiency die at or shortly after the first presentation.” A further large group of undiagnosed patients presents too late to prevent long term neurological disability. However, if the diagnosis is made early, children with this deficiency can expect to lead a full and normal life, with simple dietary treatment aimed mainly at the avoidance of fasting.
Since the first descriptions of MCAD deficiency in the early 1980s, laboratory methods for diagnosis have improved greatly. During the past decade, measurement of newborn bloodspot concentrations of octanoylcarnitine by tandem mass spectrometry has emerged as a primary screen for MCAD deficiency that has high sensitivity and specificity. Multiple analytes are now possible , phenylalanine, the screening marker for phenylketonuria, can be measured at the same time as octanoylcarnitine.
Newborn screening for MCAD deficiency is now used in many countries.
To date, in the UK more than 1.5 million newborn babies have been screened using the heelprick sample collected at 5-8 days of age and measuring octanoylcarnitine as a single biomarker. Predictive value is high-194 babies screened positive, and 152 (78%) were confirmed to have MCAD deficiency .
Editorial BMJ Screening for MCAD deficiency in newborns BMJ vol 338 p 843
- Martin Eastwood