Multiple acyl-CoA-dehydrogenase deficiency (MADD): Use of acylcarnitines and fatty acids to monitor the response to dietary treatment

The treatment of multiple acyl-CoA-dehydrogenase deficiency (MADD) includes a low-fat, low-protein, high-carbohydrate diet, avoiding long fasting peri ods. However, there is no useful biochemical marker to determine the respon se to different diets or fasting periods. The aims of this study are to rep ort a patient with MADD, diagnosed through a newborn screening program usin g tandem mass spectrometry, to assess her response to different feedings, a nd to evaluate the usefulness of acylcarnitines and FFA to monitor the resp onse to dietary changes. The patient was diagnosed at 6 d. Family history r evealed three dead siblings. Five tests were performed, one with breast mil k and the subsequent four after giving the patient a bottle of a low-fat, l ow-protein formula (F), F with glucose polymers (GP), F+GP plus uncooked co rn starch (CS), or F+GP+CS preceded by amylase. The results showed that acy lcarnitines, FFA, and total nonesterified fatty acids levels were greatly i mproved at 2 and 4 h on F+GP compared with breast milk. At 6 mo of age, the test with F+CS was repeated to assess the response to a longer fast. The r esults were similar at 2 and 4 h, but showed a marked increase of acylcarni tines, FFA, and total nonesterified fatty acids at 6 h. The increase of the se metabolites could not be avoided by the use of F+GP+CS, but was prevente d when amylase was used simultaneously. The patient is currently 3.9 y old and has normal growth and development. We conclude that diagnosis of MADD t hrough a newborn screening program using tandem mass spectrometry is suitab le; acylcarnitines and FFA are useful to monitor the response to treatment; and exogenous amylase allows the use of CS in small children with MADD. Th is therapeutic approach may be an alternative to the use of continuous over night feedings used for young children with severe fatty acid oxidation def ects. Early diagnosis and treatment may change the natural history of MADD.