Presented By:

Valentina Rovelli1,2, MD, Krista Viau1,3, RD, Marzia Pasquali1,4, PhD, Nicola Longo1,4 , MD, PhD

1Division of Medical Genetics/Pediatrics, University of Utah, Salt Lake City, UT, USA; 2Clinical Department of Pediatrics, University of Milan, San Paolo Hospital, Milan, Italy; 3Boston Children’s Hospital, Boston MA, USA; 4Department of Pathology and ARUP Laboratories, University of Utah, Salt Lake City, UT, USA.

phone #: +393331762869

BACKGROUND: VLCAD deficiency is a FAO disorder included in the recommended NBS panel in

the USA. It can have variable severity and little is known on the natural history,

geno/phenotype correlation and effectiveness of NBS.

METHODS: Retrospective data were collected from VLCADD patients to evaluate biochemical and clinical outcomes. Descriptive stats was used for qualitative variables, linear regression to correlate quantitative.

RESULTS: VLCADD (screened by elevated C14:1-carnitine levels in DBS) was more frequent in Utah than the national average in the first 10 years of screening. DNA testing or functional studies confirmed the diagnosis in 26 patients. The ACADVL c.848T>C (p.V283A) variant was the most frequent, with novel variants of unknown significance identified in some patients. Plasma C14:1-carnitine decreased with age and correlated with most other long-chain ACs species. It also correlated with CK, AST and ALT, with CK driving secondary changes in ALT and AST. There were no cases of HELLP sdr nor liver disease during

pregnancies in the mothers of VLCADD pts. No pts developed cardiac involvement after birth and all

had normal growth parameters. Clinical manifestations were related to concomitant infections and

caused alterations of biochemical (ACs) and clinically relevant (CK) parameters.

DISCUSSION: VLCADD can be identified by NBS. Most pts compliant with therapy normalized

biochemical parameters and had no major clinical manifestations. Complications were completely

prevented with limited ER visits or admissions. C14:1-carnitine, CK, AST and ALT levels correlated

with decompensations, suggesting that the stress produced by increased FAO is the primary driver of

muscle involvement. It remains unclear whether NBS is identifying less severely affected patients

compared to the pre-NBS era or if complications will arise as subjects age. Longitudinal studies are

necessary to fully understand the spectrum of morbidity caused by VLCADD.

Share this post