Clinical and Biochemical Outcome of Patients with Medium‐Chain Acyl‐CoA Dehydrogenase Deficiency

Daniela Anderson, Krista Viau, Marzia Pasquali, Nicola Longo

Division of Medical Genetics, Departments of Pediatrics and Pathology, University of Utah School of Medicine

Medium‐Chain Acyl‐CoA Dehydrogenase (MCAD) deficiency has been part of the Utah newborn screening (NBS) since 2006 and has a variable severity. Retrospective data were collected from 90 patients (n=44 female) with MCAD deficiency to compare biochemical and clinical outcomes of patients homozygous or not for the common c.985G>A mutation and patients diagnosed clinically or by NBS. The frequency of adverse events (number of hypoglycemia‐related ER, urgent care visits, and admissions) was compared by genotype and NBS status using student’s t‐test. MCAD deficiency in Utah was more frequent than the national average (1:7,738 versus 1:17,759). Overall, children with MCAD deficiency had normal growth. Homozygotes had higher NBS C8‐carnitine (23.4±19.6 versus 6.6±3.0 mmol/L) and lifetime plasma C8‐carnitine levels (6.2±5 versus 3.6±1.9 mmol/L) compared to compound heterozygotes (p<0.001 for both). The level of C8‐carnitine did not change significantly with age while C2‐carnitine decreased (p<0.001), possibly reflecting the reduction of carnitine supplementation typically seen with age. Homozygotes had significantly higher liver transaminases than compound heterozygotes (ALT 41.9±6.2 versus 31.5±3.7 U/L, AST 63.9±5.8 versus 45.7±1.8 U/L, p<0.05 for both), the clinical significance of which is unknown. On average, there were more hypoglycemia‐related adverse events observed in homozygotes compared to compound heterozygotes (1.4 versus 0.5 events/patient), and in patients diagnosed clinically compared to those diagnosed by NBS (1.9 versus 0.8 events/patient), though not statistically significant. In conclusion, homozygosity for the common mutation was associated with increased levels of C8‐carnitin and transaminases. NBS provides opportunity to reduce morbidity in all patients with MCAD deficiency.

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