Hépatologie Pédiatrique et Maladies Métaboliques, Hôpital des Enfants-CHU Toulouse, Toulouse, France.
J Inherit Metab Dis. 2013 Sep;36(5):795-803. doi: 10.1007/s10545-012-9542-6. Epub 2012 Oct 3.
Mitochondrial fatty acid β-oxidation defects (FAODs) are a group of severe inherited metabolic diseases, most of which can be treated with favorable prognosis following diagnosis. A description of the broad range of phenotypes resulting from these defects remains incomplete, and for this study, we sought to investigate the semiology at diagnosis in a country without a newborn screening program for FAODs.
Using a retrospective French multicentre study, we analyzed 187 children aged <6 years at diagnosis with FAOD confirmed by enzymatic and/or molecular analyses. Clinical and biological parameters at diagnosis were assessed to screen liver, heart, neurological, and muscle symptoms. Information concerning the long-term prognosis was also collected.
Predominant hepatic symptoms were observed in 89 % of patients regardless of the underlying defect. The most frequent symptoms observed were hepatomegaly (92 %), increased blood alanine aminotransferase (ALAT) level (82 %), and steatosis (88 %). Other frequent features included Reye syndrome (49 %), increased gamma-glutamyltranspeptidase (GGT) (37 %), and liver failure (27 %). Extrahepatic features were often associated in the foreground. Hypoglycemia (75 %), neurological (64 %), muscle (61 %), or cardiac features (55 %) [as either cardiomyopathy (47 %) or arrhythmias (31 %)] were frequently documented. Hemodynamic events (41 %) were represented by shock (31 %) or sudden death (35 %). Hyperammonemia (73 %) and hyperlactacidemia (57 %) were the two main biochemical features. Total, very-long-chain acyl-CoA dehydrogenase (VLCADD), long-chain 3-hydroxyacylCoA dehydrogenase (LCHADD), and medium-chain acyl-CoA dehydrogenase (MCADD) deficiency mortality rates were 48 %, 60 %, 63 %, and 20 % respectively.
This study presents clinical features of a large cohort of patients with FAODs in a country without neonatal screening for FAODs. Our results highlight liver as the main organ involved at diagnosis regardless of age at diagnosis, classical phenotype (i.e., cardiac, hepatic, or muscular), or enzyme deficiency. Although steatosis may be observed in various inherited metabolic defects, it is a reliable indicator of FAOD and should prompt systematic screening when the diagnosis is suspected. The poor long-term prognoses reported are a strong argument for inclusion of FAODs in newborn screening programs.
线粒体脂肪酸β氧化缺陷（FAODs）是一组严重的遗传性代谢疾病，大多数在诊断后通过有利的治疗可获得良好的预后。由于这些缺陷导致的广泛表型仍不完全清楚，因此本研究旨在调查一个没有 FAOD 新生儿筛查计划的国家的诊断时的首发症状。
采用回顾性法国多中心研究，分析了 187 例年龄<6 岁的 FAOD 确诊患儿，这些患儿的酶和/或分子分析均证实存在 FAOD。对诊断时的临床和生物学参数进行评估，以筛查肝脏、心脏、神经和肌肉症状。还收集了有关长期预后的信息。
无论潜在缺陷如何，89%的患者均以明显的肝脏症状为首发表现。最常见的症状包括肝肿大（92%）、丙氨酸氨基转移酶（ALAT）水平升高（82%）和脂肪变性（88%）。其他常见的表现包括瑞氏综合征（49%）、γ-谷氨酰转肽酶（GGT）升高（37%）和肝衰竭（27%）。肝外表现常同时出现。低血糖（75%）、神经（64%）、肌肉（61%）或心脏（55%）表现[如心肌病（47%）或心律失常（31%）]常被记录在案。血液动力学事件（41%）表现为休克（31%）或猝死（35%）。高血氨症（73%）和高乳酸血症（57%）是两种主要的生化特征。总酰基辅酶 A 脱氢酶（VLCADD）、长链 3-羟酰基辅酶 A 脱氢酶（LCHADD）和中链酰基辅酶 A 脱氢酶（MCADD）缺陷的死亡率分别为 48%、60%、63%和 20%。
本研究在一个没有 FAOD 新生儿筛查的国家，对大量 FAOD 患儿的临床特征进行了描述。我们的结果强调了肝脏是诊断时主要受累的器官，无论诊断时的年龄、经典表型（即心脏、肝脏或肌肉）或酶缺乏如何。虽然脂肪变性可能在各种遗传性代谢缺陷中观察到，但它是 FAOD 的一个可靠指标，当怀疑诊断时应进行系统筛查。报道的不良长期预后强烈支持将 FAOD 纳入新生儿筛查计划。
