Southern Illinois University, Springfield, IL, USA.
J Investig Med High Impact Case Rep. 2021 Jan-Dec;9:23247096211019543. doi: 10.1177/23247096211019543.
Primary carnitine deficiency (PCD) is a rare autosomal recessive disorder caused by loss of function mutations in the solute carrier family 22 member 5 () gene that encodes a high-affinity sodium-ion-dependent organic cation transporter protein (OCTN2). Reduced carnitine transport results in diminished fatty acid oxidation in heart and skeletal muscle and carnitine wasting in urine. We present a case of PCD diagnosed in an adult female after a positive newborn screen (NBS) for PCD that was not confirmed on follow-up testing. The mother was referred for evaluation of persistent fatigue and possible hypothyroidism even though all measurements of thyroid-stimulating hormone were well within the range of 0.4 to 2.5 mIU/L expected for reproductive-age women. She was found to have unequivocally low levels of both total carnitine and carnitine esters, and genetic testing revealed compound heterozygosity for 2 SLC22A5 mutations. One mutation (c.34G>A [p.Gly12Ser]) is a known missense mutation with partial OCTN2 activity, but the other mutation (c.41G>A [p.Trp14Ter]) is previously unreported and results in a premature stop codon and truncated OCTN2. This case illustrates that some maternal inborn errors of metabolism can be identified by NBS and that maternal carnitine levels should be checked after a positive NBS test for PCD.
原发性肉碱缺乏症（PCD）是一种罕见的常染色体隐性遗传疾病，由溶质载体家族 22 成员 5（SLC22A5）基因突变引起，该基因突变导致编码高亲和力钠离子依赖性有机阳离子转运蛋白（OCTN2）的功能丧失。肉碱转运减少导致心脏和骨骼肌脂肪酸氧化减少和尿中肉碱丢失。我们报告了一例成年女性 PCD 病例，该患者在新生儿筛查（NBS）中呈阳性，但在后续检测中未得到确认。该患者的母亲因持续性疲劳和可能的甲状腺功能减退而被转介评估，尽管所有促甲状腺激素测量值均在预期生育年龄女性 0.4 至 2.5 mIU/L 范围内。她被发现总肉碱和肉碱酯水平均明显降低，基因检测显示 2 种 SLC22A5 突变的复合杂合性。一种突变（c.34G>A [p.Gly12Ser]）是一种已知的错义突变，具有部分 OCTN2 活性，但另一种突变（c.41G>A [p.Trp14Ter]）以前未报道过，导致提前终止密码子和截断的 OCTN2。该病例表明，一些母体先天性代谢错误可以通过 NBS 识别，并且在 PCD 的 NBS 检测阳性后应检查母体肉碱水平。
