Unusual presentation of propionic acidaemia as isolated cardiomyopathy.
Unusual presentation of propionic acidaemia as isolated cardiomyopathy.
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DOI：
10.1007/s10545-009-1084-1
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发表时间：
2009-12
影响因子：
4.2
通讯作者：
Chung, W. K.
中科院分区：
文献类型：
--
作者：
Lee, T. M.;Addonizio, L. J.;Barshop, B. A.;Chung, W. K.
丙酸血症(PA)是一种常染色体隐性遗传病，由丙酰辅酶A羧基酶(PCC)缺乏引起。在几乎所有报道的PA病例中，表型包括代谢性酸中毒和/或神经缺陷。我们报告一位14岁患有PA的亚洲男性患者，他表现为孤立性心肌病，没有任何代谢性酸中毒或任何神经认知缺陷的表现。在常规的代谢筛查中，患者被发现有提示PA的尿液有机酸。生化和遗传学特征证实PCCB存在两个新的突变：IVS7+2 T>；G(c.763+2 T>；G)和p.R410Q(c.1229 G>；A)。残留的酶活性可能解释了我们病人的轻微表型。剪接突变往往导致较温和的表型，因为这些突变仍然可能产生少量的正常酶。此外，类似的p.R410W突变已被证明具有部分残存活性。此外，此病例说明了作为PA的唯一临床表现的孤立性心肌病的重要但未被认识的表现。所有患有心肌病的儿科患者都应该进行彻底的代谢评估。这样的评估对临床管理和遗传咨询具有重要的意义。
Propionic acidemia (PA) is an autosomal recessive disease that results from deficiency of propionyl-CoA carboxylase (PCC). In virtually all reported cases of PA, the phenotype includes metabolic acidosis and/or neurological deficits. We report on a 14-year-old Asian male with PA who presented with isolated cardiomyopathy without any episodes of metabolic acidosis or evidence of any neurocognitive deficits. On routine metabolic screening, the patient was found to have urine organic acids suggestive of PA. Biochemical and genetic characterization confirmed a PCC deficiency with two novel mutations in PCCB: IVS7+2 T>G (c.763+2 T>G) and p.R410Q (c.1229 G>A). Residual enzyme activity likely explains our patient’s mild phenotype. Splicing mutations tend to result in a milder phenotype as these mutations may still produce small amounts of normal enzyme. In addition, the similar p.R410W mutation has been shown to have partial residual activity. Moreover, this case illustrates the important but under-recognized manifestation of isolated cardiomyopathy as the sole clinical presentation in PA. A thorough metabolic evaluation should be performed in all pediatric patients with cardiomyopathy. Such an evaluation has important implications for clinical management and genetic counseling.
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