Prietsch Viola, Mayatepek Ertan, Krastel Hermann, Haas Dorothea, Zundel Dorothee, Waterham Hans R, Wanders Ronald J A, Gibson K Michael, Hoffmann Georg F
General Pediatrics, University of Heidelberg, Federal Republic of Germany.
Pediatrics. 2003 Feb;111(2):258-61. doi: 10.1542/peds.111.2.258.
Mevalonic aciduria as a result of mevalonate kinase deficiency is an inborn error of cholesterol biosynthesis characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Pathogenic mutations in the mevalonate kinase gene in both disorders have demonstrated a common genetic basis. Our aim was to describe the clinical picture of adolescent patients with mevalonate kinase deficiency and to expand the clinical and biochemical spectrum of mevalonate kinase deficiency, particularly with regard to HIDS.
We report the clinical history and biochemical findings of 3 patients with mevalonic aciduria.
In 2 siblings with mevalonic aciduria, a 15-year-old girl and a 14-year-old boy, the phenotype shifted with age. Ataxia has become the predominant clinical manifestation, whereas the febrile attacks occur less frequently but as yet have not disappeared. Both of them show marked elevations of immunoglobulin D (IgD). Psychomotor development is retarded but not regressive. Short stature developed in both patients. Additional findings include the development of retinal dystrophy and cataracts in both of them. The third patient is a 6-year-old boy who presented at the age of 5 years with cerebellar ataxia and retinal dystrophy. He is different from all known patients with mevalonic aciduria because of the mild neurologic involvement and because he has never developed febrile crises. In addition, levels of IgD were repeatedly normal.
The clinical and biochemical spectrum of patients with mevalonic aciduria is heterogeneous. Manifestations of the disease seem to be age dependent, as evident from this first report of adolescent patients. In patients who survive infancy, short stature, ataxia caused by cerebellar atrophy, and ocular involvement with retinal dystrophy become predominant findings. Recurrent febrile crises seem to diminish with increasing age and may not even be an obligatory finding. Elevation of IgD is most likely a secondary phenomenon that seems to be linked to recurrent febrile crises.
由于甲羟戊酸激酶缺乏导致的甲羟戊酸尿症是一种胆固醇生物合成的先天性代谢缺陷病，其特征为畸形、精神运动发育迟缓、进行性小脑共济失调以及反复发热性危象，通常在婴儿早期出现，伴有肝脾肿大、淋巴结病、关节痛和皮疹。发热性危象与高免疫球蛋白D和周期性发热综合征（HIDS）中观察到的相似。这两种疾病中甲羟戊酸激酶基因的致病突变已显示出共同的遗传基础。我们的目的是描述青少年甲羟戊酸激酶缺乏患者的临床症状，并扩展甲羟戊酸激酶缺乏的临床和生化谱，特别是关于HIDS方面。
我们报告了3例甲羟戊酸尿症患者的临床病史和生化检查结果。
在2例患甲羟戊酸尿症的同胞中，一名15岁女孩和一名14岁男孩，其表型随年龄变化。共济失调已成为主要临床表现，而发热发作频率降低，但尚未消失。他们两人的免疫球蛋白D（IgD）均显著升高。精神运动发育迟缓但无倒退。两名患者均出现身材矮小。其他发现包括两人均出现视网膜营养不良和白内障。第三名患者是一名6岁男孩，5岁时出现小脑共济失调和视网膜营养不良。他与所有已知的甲羟戊酸尿症患者不同，因为神经系统受累较轻且从未出现发热性危象。此外，IgD水平多次正常。
甲羟戊酸尿症患者的临床和生化谱具有异质性。从这份关于青少年患者的首次报告可以明显看出，该疾病的表现似乎与年龄有关。在婴儿期存活下来的患者中，身材矮小、小脑萎缩引起的共济失调以及视网膜营养不良导致的眼部受累成为主要表现。反复发热性危象似乎随着年龄增长而减少，甚至可能并非必然出现。IgD升高很可能是一种继发现象，似乎与反复发热性危象有关。
