Carnitine transporter and holocarboxylase synthetase deficiencies in the Faroe Islands
Carnitine transporter and holocarboxylase synthetase deficiencies in the Faroe Islands
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DOI：
10.1007/s10545-007-0527-9
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Skovby, F.
中科院分区：
文献类型：
--
作者：
Lund, A. M.;Joensen, F.;Skovby, F.
肉毒碱转运蛋白缺乏症（CTD）和全羧化酶合成酶缺乏症（HLCSD）在法罗群岛与其他地区相比是常见的，并且可以治疗这两种疾病。为了评估新生儿筛查的可行性在法罗群岛，我们研究了检测在新生儿期的串联质谱，载波频率，临床表现，CTD和HLCSD的治疗效果。我们发现了来自5个家庭的11例CTD患者和来自5个家庭的8例HLSD患者。这两种疾病的自然史在患者中差异很大，从可能死于疾病的患者到无症状个体。所有有症状的患者对补充左旋肉碱（CTD病例）或生物素（HLCSD病例）反应良好，但仅在早期治疗时。估计这两种疾病的携带者频率约为1：20，表明一些酶缺乏的个体仍未被诊断出来。前瞻性和回顾性串联质谱法（MS/MS）分析的肉毒碱从atally获得的滤纸干血斑样本（DBSS）发现8的10个CTD的个人时，使用C-0和C-2作为标记（当前算法）和10的10时，仅使用C-0作为标记。MS/MS分析发现6例HLCSD中5例。这是第一个研究报告成功的新生儿MS/MS分析诊断HLCSD。我们的结论是，CTD和HLCSD是相对频繁的法罗群岛，并与变量的临床表现，并通过新生儿筛查早期治疗的诊断将确保一个良好的结果。
Carnitine transporter deficiency (CTD) and holocarboxylase synthetase deficiency (HLCSD) are frequent in The Faroe Islands compared to other areas, and treatment is available for both disorders. In order to evaluate the feasibility of neonatal screening in The Faroe Islands we studied detection in the neonatal period by tandem mass spectrometry, carrier frequencies, clinical manifestations, and effect of treatment of CTD and HLCSD. We found I I patients with CTD from five families and 8 patients with HLCSD from five families. The natural history of both disorders varied extensively among patients, ranging from patients who presumably had died from their disease to asymptomatic individuals. All symptomatic patients responded favourably to supplementation with L-carnitine (in case of CTD) or biotin (in case of HLCSD), but only if treated early. Estimates of carrier frequency of about 1:20 for both disorders indicate that some enzyme-deficient individuals remain undiagnosed. Prospective and retrospective tandem mass spectrometry (MS/MS)analyses of carnitines from neonatally obtained filter-paper dried blood-spot samples (DBSS) uncovered 8 of 10 individuals with CTD when using both C-0 and C-2 as markers (current algorithm) and 10 of 10 when using only C-0 as marker. MS/MS analysis uncovered 5 of 6 patient with HLCSD. This is the first study to report successful neonatal MS/MS analysis for the diagnosis of HLCSD. We conclude that CTD and HLCSD are relatively frequent in The Faroe Islands and are associated with variable clinical manifestations, and that diagnosis by neonatal screening followed by early therapy will secure a good outcome.