■细胞内钴胺素代谢途径最常见的疾病是联合甲基丙二酸血症和高半胱氨酸血症,cblC类型(cblC)。其临床范围存在差异,从高度致命的严重新生儿发作形式到较温和的晚期发作形式。在这项研究中,发现了首例无症状的中国妇女,由于同型半胱氨酸水平升高,在产前诊断时先天性钴胺素(cblC型)代谢缺陷。
■先证者,一个29岁的G1P0母亲所生的男孩,因喂养障碍入院当地医院,智力残疾,癫痫发作,小头畸形,以及异眼。尿甲基丙二酸的水平升高。同样发现的是血液丙酰肉碱(C3)和丙酰肉碱/游离肉碱比率(C3/C0)增加,蛋氨酸水平降低。血浆总同型半胱氨酸水平升高至101.04μmol/L(正常<15μmol/L)。支持联合甲基丙二酸血症和同型半胱氨酸血症的临床诊断。四年后,男孩的母亲再次结婚,并在她最后一次月经期后正好15周来到我们这里进行产前诊断。随后,羊水丙二酸甲酯增加。羊水总同型半胱氨酸水平略高。同样观察到相当高的羊水C3。此外,在31.96和39.35μmol/L时,血浆和尿液中的总同型半胱氨酸分别显着增加。MMACHC基因测序后,发现那个男孩,先证者在c.658_660delAAG处携带MMACHC的纯合突变。而男孩的母亲,她在MMACHC中携带两个突变:c.658_660delAAG和c.617G>A。胎儿是MMACHC基因的携带者。常规治疗后,母亲在怀孕过程中没有症状,她生下了一个健康的男孩。
■可变且非特异性的症状表现为cblC型甲基丙二酸血症合并同型半胱氨酸血症。建议将生化测定和突变分析作为关键的补充技术。
UNASSIGNED: The most common disorder of the intracellular cobalamin metabolism pathway is the combined methylmalonic acidemia and
homocysteinemia, cblC type (cblC). There is a variation in its clinical spectrum ranging from severe neonatal-onset forms that are highly fatal to later-onset forms which are milder. In this study, the first case of an asymptomatic Chinese woman with a defect in congenital cobalamin (cblC type) metabolism at prenatal diagnosis due to elevated homocysteine level is identified.
UNASSIGNED: The proband, a male child born to a 29-year-old G1P0 mother, admitted to local hospital with feeding disorder, intellectual disability, seizures, microcephaly, as well as heterophthalmos. The level of the urine methylmalonic was elevated. Equally found were increased blood propionylcarnitine (C3) and propionylcarnitine/free carnitine ratio (C3/C0) and decreased methionine levels. The plasma total homocysteine level was elevated at 101.04 μmol/L (normal < 15 μmol/L). The clinical diagnosis of combined methylmalonic acidemia and
homocysteinemia was supported. Four years later, the mother of the boy married again and came to us for prenatal diagnosis exactly 15 weeks after her last menstrual period. Subsequently, there is an increase in the amniotic fluid methylmalonate. The level of the amniotic fluid total homocysteine was marginally high. A considerably elevated amniotic fluid C3 was equally observed. In addition, there is a respective significant increase in the plasma and urine total homocysteine at 31.96 and 39.35 μmol/L. After the sequencing of MMACHC genes, it is found that the boy, a proband carried a homozygous mutation of the MMACHC at c.658_660delAAG. While the boy\'s mother, she carries two mutations in MMACHC: c.658_660delAAG and c.617G>A. The fetus is a carrier of the MMACHC gene. Following the administration of routine treatment, the mother remained symptom-free in the course of pregnancy, and she gave birth to a healthy boy.
UNASSIGNED: Variable and nonspecific symptoms characterized the cblC type of methylmalonic acidemia combined with
homocysteinemia. Both biochemical assays and mutation analysis are recommended as crucial complementary techniques.