Communicated Johannes Zschocke
Genotype–phenotype correlation in primary carnitine deficiency†
Article first published online: 11 OCT 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 1, pages 118–123, January 2012
How to Cite
Rose, E. C., di San Filippo, C. A., Ndukwe Erlingsson, U. C., Ardon, O., Pasquali, M. and Longo, N. (2012), Genotype–phenotype correlation in primary carnitine deficiency. Hum. Mutat., 33: 118–123. doi: 10.1002/humu.21607
- Issue published online: 14 DEC 2011
- Article first published online: 11 OCT 2011
- Accepted manuscript online: 15 SEP 2011 01:53PM EST
- Manuscript Accepted: 25 AUG 2011
- Manuscript Received: 7 JUN 2011
- National Institutes of Health. Grant Number: R01 DK 53824
- carnitine deficiency;
Primary carnitine deficiency is caused by defective OCTN2 carnitine transporters encoded by the SLC22A5 gene. Lack of carnitine impairs fatty acid oxidation resulting in hypoketotic hypoglycemia, hepatic encephalopathy, skeletal and cardiac myopathy. Recently, asymptomatic mothers with primary carnitine deficiency were identified by low carnitine levels in their infant by newborn screening. Here, we evaluate mutations in the SLC22A5 gene and carnitine transport in fibroblasts from symptomatic patients and asymptomatic women. Carnitine transport was significantly reduced in fibroblasts obtained from all patients with primary carnitine deficiency, but was significantly higher in the asymptomatic women's than in the symptomatic patients' fibroblasts (P < 0.01). By contrast, ergothioneine transport (a selective substrate of the OCTN1 transporter, tested here as a control) was similar in cells from controls and patients with carnitine deficiency. DNA sequencing indicated an increased frequency of nonsense mutations in symptomatic patients (P < 0.001). Expression of the missense mutations in Chinese hamster ovary (CHO) cells indicated that many mutations retained residual carnitine transport activity, with no difference in the average activity of missense mutations identified in symptomatic versus asymptomatic patients. These results indicate that cells from asymptomatic women have on average higher levels of residual carnitine transport activity as compared to that of symptomatic patients due to the presence of at least one missense mutation. Hum Mutat 33:118–123, 2012. © 2011 Wiley Periodicals, Inc.