Importance of enzyme activity measurement for MCAD deffiency classification in patients with inconclusive results. Case report.

BACKGROUND

Medium-chain fatty acid acyl-CoA dehydrogenase (MCAD) is a mitochondrial enzyme that converts medium-chain (MC) fatty acids into short-chain fatty acids and acetyl-CoA for its use during fasting periods. MCAD deficiency is one of the most common fatty acids b-oxidation disorders. Clinical symptoms include hypoketotic hypoglycemia, vomiting, lethargy, seizures and coma, and may appear since first weeks of life. It has a good prognosis if an early diagnosis is established since it has an easy management. The diagnosis is made by neonatal screening of the MC acylcarnitine concentrations and confirmation by biochemical and genetic analysis. Determination of enzyme activity (EA) can also be performed if necessary.

CLINICAL CASE

Newborn in which an increase in acylcarnitines in blood in neonatal screening is observed (C6: 0,31umol/L, VR<0,13; C8: 0,77umol/L, VR<0,13; C10: 0,20umol/L, VR<0,13; C8/C10: 3,94umol/L VR:<2,1; C8/C10: 0,05umol/L VR:<0,006).

RESULTS

Urinary organic acids revealed an increase in suberic acid, hexanoylglycine and suberylglycine. The genetic study classified the patient as compound heterozygous for two variants, c.430A>T, and C.709-13A>G. His parents were both classified as heterozygous carriers of a MCAD deficiency variant. The determination of EA revealed an activity of 16%, consistent with MCAD deficiency.

DISCUSSION/CONCLUSION

Neonatal screening together with genetic diagnosis allow characterizing most MCAD patients. However, in those patients in whom the genetics and biochemical results are doubtful, the measurement of EA can be an useful determination for the final classification of the patient. In this case, C8 concentrations corresponded to a typical heterozygous profile while C8/C10 ratio was more indicative of an homozygous patient. Measurement of EA revealed that, although the patient was heterozygous, the presence of these particular mutations elevated the C8/C10 ratio to typical concentrations of an homozygous patient.