Neonatal screening for defects of the mitochondrial trifunctional protein

Long-chain l-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been included in the routine neonatal screening program by the German screening commission. As tandem mass spectrometry (TMS) does not discriminate between the different defects of the mitochondrial trifunctional protein (MTP) screening for isolated LCHAD deficiency includes the detection of long-chain 3-ketoacyl-CoA thiolase and complete MTP deficiencies as well. We identified 11 patients with abnormalities of the MTP out of 1.2 million newborns screened in our laboratory during the last 6 years. Treatment was started on the day the screening result was obtained (day 3 to day 9 of life). Seven of these newborns developed satisfactorily during an observation period of up to 64 months. They had isolated LCHAD deficiency, four of them caused by the typical mutation (1528 G>C), three others had no molecular genetic analysis done or were shown to have previously unknown mutations. Four children did not survive, two of them showing complete deficiency of MTP and two showing deficiency of long-chain 3-ketoacyl-CoA thiolase. We conclude that, despite the rarity of the disease, screening for MTP deficiencies is justified based on the following criteria: improved quality of life for patients with isolated LCHAD deficiency, absence of stigmatisation of babies showing mild variants without necessity of treatment, no significant increase of the total number of false positive screening results, no false negative results to our knowledge. Finally, extension of analysis to MTP deficiencies is achieved without additional costs for screening laboratories already using TMS.