Typical cMRI Pattern as Diagnostic Clue for D-Bifunctional Protein Deficiency Without Apparent Biochemical Abnormalities in Plasma
Typical cMRI Pattern as Diagnostic Clue for D-Bifunctional Protein Deficiency Without Apparent Biochemical Abnormalities in Plasma
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DOI：
10.1002/ajmg.a.33677
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发表时间：
2010-11-01
影响因子：
2
通讯作者：
Gaertner, Jutta
中科院分区：
文献类型：
--
作者：
Gronborg, Sabine;Kraetzner, Ralph;Gaertner, Jutta
D-双功能蛋白缺乏症(DBPD)是一种常染色体隐性遗传病，由过氧化物酶-β氧化缺陷引起。大多数患者患有严重的神经系统疾病，伴有新生儿低眼压和癫痫发作，并在生命的头两年内死亡。很少有患者表现出较轻的临床表型和较长的生存期。诊断依赖于临床表现、包括血浆中极长链脂肪酸(VLCFA)在内的过氧化体标志物的测量，然后是成纤维细胞的酶研究和基因测试。在较轻的病例中很难确定诊断，特别是如果血浆中VLCFA浓度不是或只是轻微升高。我们报告了最初对血浆VLCFA的测量没有提示过氧素体疾病的兄弟姐妹。然而，CMRI显示了一种典型的先天过氧化病伴大脑和小脑白质脑病、坐骨神经周围多小脑回和额顶顶粗回的模式。在CMRI发现的提示下，反复测量血浆中的过氧化物体代谢物，结果显示数值处于正常上限或轻度升高范围，并导致进一步的诊断步骤。编码D-双功能蛋白(DBP)的HSD17B4基因错义突变(T15A)可确诊为III型DBPD。我们的结论是，CMRI中典型的“过氧化物型模式”，包括大脑和小脑白质脑病、坐骨神经周围多小脑回和厚脑回，是诊断DBPD的有价值的线索，特别是在没有或仅有非常轻微的血浆异常的情况下。
D-bifunctional protein deficiency (DBPD) is an autosomal recessive disease caused by a defect in peroxisomal beta-oxidation. The majority of patients suffer from a severe neurological disease with neonatal hypotonia and seizures and die within the first 2 years of life. Few patients show milder clinical phenotypes with prolonged survival. The diagnosis relies on the clinical presentation, measurement of peroxisomal markers, including very long chain fatty acids (VLCFA) in plasma, followed by enzymatic studies in fibroblasts and genetic testing. Diagnosis can be difficult to establish in milder cases, especially if VLCFA concentration in plasma is not or only mildly elevated. We report on siblings in which initial measurement of plasma VLCFA did not indicate a peroxisomal disease. Nevertheless, cMRI showed a pattern typical for an inborn peroxisomal disease with cerebral and cerebellar leukencephalopathy, perisylvic polymicrogyria, and frontoparietal pachygyria. Repeated measurements of peroxisomal metabolites in plasma prompted by the cMRI findings showed values in the upper normal or mildly elevated range and led to further diagnostic steps. The diagnosis of a type III DBPD with a missense mutation (T15A) in the HSD17B4 gene, coding for D-bifunctional protein (DBP), could be established. We conclude that a typical "peroxisomal pattern'' in cMRI including cerebral and cerebellar leukencephalopathy, perisylvic polymicrogyria and pachygyria is a valuable clue to the diagnosis of DBPD, especially in cases with no or only very mild abnormalities in plasma. (C) 2010 Wiley-Liss, Inc.