Doyle Samantha, O'Byrne James J, Nesbitt Mandy, Murphy Daniel N, Abidin Zaza, Byrne Niall, Pastores Gregory, Kirk Richard, Treacy Eileen P
National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital Dublin Ireland.
School of Medicine and Medical Sciences, University College Dublin Dublin Ireland.
JIMD Rep. 2019 Mar 25;47(1):35-40. doi: 10.1002/jmd2.12028. eCollection 2019 May.
Inherited trimethylaminuria (TMAU), a rare genetic disorder of hepatic metabolism of trimethylamine (TMA) causing excessive accumulation of malodorous trimethylamine (TMA), is a socially distressing disorder. Diagnosis is made by biochemical analysis of urine, with the calculation of flavin monooxygenase trimethylamine conversion capacity. Genetic testing, sequencing the entire coding region of the gene has been recommended for affected individuals who convert less than 90% of the total TMA load to TMAO.
Genetic analysis was undertaken for 13 Irish patients with TMAU of varying phenotypic severity (three severe, six moderate, and four mild).
A genetic diagnosis was made for seven patients, including for five of the nine moderate to severely affected cases. We noted the c.913G>T;p.(Glu305*) and c.458C>T;p.(Pro153Leu) mutations in this Irish population with severe TMAU which is consistent with our earlier findings in Australian and North American families of Irish and British descent.Three individuals were noted to be homozygous for the common variant haplotype c.472G>A;923A>G;p.(Glu158Lys);(Glu308Gly). We also identified three novel variants in this population, which are likely to be pathogenic: c.682G>A;p(Gly228Ser), c.694G>T:p(Asp232Tyr), and c.989G>A;p.(Gly330Glu).
Urinary biochemical analysis probably remains the first line diagnostic approach to classify the various types of TMAU. gene analysis is likely only to be informative for certain presentations of TMAU.
遗传性三甲胺尿症（TMAU）是一种罕见的肝脏三甲胺（TMA）代谢遗传疾病，可导致有恶臭的三甲胺（TMA）过度蓄积，是一种令人困扰的疾病。通过对尿液进行生化分析并计算黄素单加氧酶三甲胺转化能力来进行诊断。对于将总TMA负荷转化为氧化三甲胺（TMAO）少于90%的受影响个体，建议进行基因检测，即对该基因的整个编码区进行测序。
对13名爱尔兰TMAU患者进行了基因分析，这些患者具有不同的表型严重程度（3例严重，6例中度，4例轻度）。
7名患者得到了基因诊断，其中包括9例中度至重度受影响病例中的5例。我们在这个患有严重TMAU的爱尔兰人群中发现了c.913G>T;p.(Glu305*)和c.458C>T;p.(Pro153Leu)突变，这与我们之前在澳大利亚以及北美爱尔兰和英国后裔家族中的发现一致。有3个人被发现是常见变异单倍型c.472G>A;923A>G;p.(Glu158Lys);(Glu308Gly)的纯合子。我们还在这个人群中鉴定出了3个可能致病的新变异：c.682G>A;p(Gly228Ser)、c.694G>T:p(Asp232Tyr)和c.989G>A;p.(Gly330Glu)。
尿液生化分析可能仍然是对各种类型TMAU进行分类的一线诊断方法。基因分析可能仅对TMAU的某些表现有参考价值。
