Ozand P T, Rashed M, Millington D S, Sakati N, Hazzaa S, Rahbeeni Z, al Odaib A, Youssef N, Mazrou A, Gascon G G
Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Brain Dev. 1994 Nov;16 Suppl:12-22. doi: 10.1016/0387-7604(94)90092-2.
Five infants from 3 families, one Egyptian, two Yemeni, are described with a progressive encephalopathy, four of whom have been studied in detail. All patients showed vascular lesions of the skin, characterized by waxing and waning petechiae and ecchymoses. Acrocyanosis was present in three patients. All patients showed retinal lesions characterized by tortuous veins. Protracted diarrhea was not a consistent finding, although they had metabolic crisis in association with diarrhea. They did not show failure to thrive. The neurologic symptoms were indicative of a progressive pyramidal tract disease. Three patients died following sudden emergence of severe basal ganglia, putaminal and head of caudate lesions. In one patient the CT changes in brain were suggestive of infarction. The patients who died manifested pulmonary congestion, or wet lung, and respiratory difficulties during the terminal stage of the disease. In all patients before and during the terminal event, mild-to-moderate hematuria, and in two RBC in CSF, was observed. In one patient there was mild hemoperitoneum at the terminal event. The urine organic acids indicated increased excretion of ethylmalonic, methylsuccinic, glutaric, and adipic acids. The patients invariably showed lactic acidosis, but no ketosis, during and in between the acidotic attacks of the disease. The acylcarnitine profile in blood of two patients showed a pronounced increase in C4 and C5 carnitine esters. In three patients, biopsies from petechiae indicated absence of an immune event, showing only fresh hemorrhage. An immunologic study in one patient was normal for the suppressor:cytotoxic lymphocyte ratio and concentration of interleukin-2 receptor during and in between hemorrhagic attacks. The cytochrome c oxidase activity in fibroblasts was normal. The rate of oxidation of glucose, leucine, isoleucine, valine, propionate and butyrate by fibroblasts was normal. The disease is not responsive to treatment with riboflavin, ascorbic acid, vitamin E, glycine, or carnitine. One patient remained stable on prolonged large doses of methylprednisolone. The biochemical defect leading to ethylmalonic aciduria in this disease remains unknown.
本文描述了来自3个家庭的5名婴儿，其中1名埃及人，2名也门人，患有进行性脑病，对其中4名患者进行了详细研究。所有患者均表现出皮肤血管病变，其特征为瘀点和瘀斑反复出现。3名患者出现肢端青紫症。所有患者均表现出以迂曲静脉为特征的视网膜病变。尽管患者在腹泻时会出现代谢危机，但持续性腹泻并非常见症状。他们没有出现生长发育迟缓。神经系统症状提示为进行性锥体束疾病。3名患者在突然出现严重的基底神经节、壳核和尾状核头部病变后死亡。1名患者脑部的CT变化提示梗死。死亡患者在疾病末期出现肺充血或湿肺以及呼吸困难。在所有患者终末期事件之前及期间，均观察到轻度至中度血尿，2名患者脑脊液中出现红细胞。1名患者在终末期事件时出现轻度腹腔积血。尿有机酸显示乙基丙二酸、甲基琥珀酸、戊二酸和己二酸排泄增加。在疾病的酸中毒发作期间及发作间期，患者始终表现为乳酸酸中毒，但无酮症。2名患者血液中的酰基肉碱谱显示C4和C5肉碱酯显著增加。3名患者瘀点活检显示无免疫反应，仅见新鲜出血。1名患者在出血发作期间及发作间期的免疫抑制细胞毒性淋巴细胞比率和白细胞介素-2受体浓度的免疫学研究结果正常。成纤维细胞中的细胞色素c氧化酶活性正常。成纤维细胞对葡萄糖、亮氨酸、异亮氨酸、缬氨酸、丙酸盐和丁酸盐的氧化速率正常。该疾病对核黄素、抗坏血酸、维生素E、甘氨酸或肉碱治疗无反应。1名患者长期大剂量使用甲基泼尼松龙后病情稳定。导致该疾病出现乙基丙二酸尿症的生化缺陷仍不清楚。
