Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening.
Carnitine uptake defect (CUD) is an autosomal recessive fatty acid oxidation defect caused by a deficiency of the high-affinity carnitine transporter OCTN2. CUD patients may present with hypoketotic hypoglycemia, hepatic encephalopathy or dilated cardiomyopathy. Tandem mass spectrometry screening of newborns can detect CUD, although transplacental transport of free carnitine from the mother may cause a higher free carnitine level and cause false negatives during newborn screening. From Jan 2001 to July 2009, newborns were screened for low free carnitine levels at the National Taiwan University Hospital screening center. Confirmation tests included dried blood spot free acylcarnitine levels and mutation analyses for both babies and their mothers. Sixteen newborns had confirmation tests for persistent low free carnitine levels; four had CUD, six had mothers with CUD, and six cases were false positives. All babies born to mothers with CUD had transient carnitine deficiency. The six mothers with CUD were put on carnitine supplementation (50-100mg/kg/day). One mother had dilated cardiomyopathy at diagnosis and her cardiac function improved after treatment. Analysis of the SLC22A5 gene revealed that p.S467C was the most common mutation in mothers with CUD, while p.R254X was the most common mutation in newborns and children with CUD. Newborn screening allows for the detection of CUD both in newborns and mothers, with an incidence in newborns of one in 67,000 (95% CI: one in 31,600-512,000) and a prevalence in mothers of one in 33,000 (95% CI: one in 18,700-169,000). Detection of CUD in mothers may prevent them from developing dilated cardiomyopathy.
Lee
Ni-Chung
NC
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Tang
Nelson Leung-Sang
NL
Chien
Yin-Hsiu
YH
Chen
Chun-An
CA
Lin
Sho-Juan
SJ
Chiu
Pao-Chin
PC
Huang
Ai-Chu
AC
Hwu
Wuh-Liang
WL
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000209:etiology; D002331:Carnitine / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D005188:False Negative Reactions; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D009035:Mothers; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods; D027701:Organic Cation Transport Proteins / Q000172:deficiency / Q000235:genetics*; D000074058:Solute Carrier Family 22 Member 5; D013624:Taiwan / Q000453:epidemiology; D053719:Tandem Mass Spectrometry
D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine