目的 探讨迟发型非典型异戊酸尿症患儿的临床、治疗及IVD基因突变特点。方法 3例非典型异戊酸尿症患儿,经尿液有机酸、血液酯酰肉碱谱分析发现异戊酸尿症,并经IVD基因突变检测确诊。患儿给予左卡尼汀、甘氨酸补充治疗及限亮氨酸饮食干预并进行随访。结果 3例患儿于1~2岁间发病,有不明原因呕吐、嗜睡,伴汗脚样体臭及代谢性酸中毒。3例患儿智力正常,均伴随显著的白细胞减少症,其中1例伴红细胞减少症。3例患儿血液异戊酰肉碱水平显著增高(4.6~8.2 μmol/L),尿液异戊酰甘氨酸水平显著增高(36.1~ 1 783.56 mmol/mmol 肌酐)。3例患儿IVD基因共检出6种突变,其中已知突变4种(c.157C>T,c.214 G>A,c.1183C>G,c.1208A>G),新突变2种(c.1039G>A,c.1076A>G)。经治疗后患儿顺利康复,目前1岁7个月~14岁,智力、运动及体格发育正常。结论 迟发性异戊酸尿症临床表现复杂,于婴幼儿期发病,可有反复呕吐、酸中毒,通过血液酰基肉碱谱、尿液有机酸分析及基因分析确诊,左卡尼汀及饮食干预,疗效显著。
华瑛
,
丁圆
,
刘玉鹏
,
王峤
,
秦亚萍
,
杨艳玲
,
吴桐菲
,
张尧
,
李溪远
,
宋金青
,
李梦秋
. 3 例非典型异戊酸尿症患儿临床及基因型研究[J]. 临床儿科杂志, 2014
, 32(12)
: 1107
.
DOI: 10.3969 j.issn.1000-3606.2014.12.002
Objective To explore the clinical, therapeutic and genetic features of IVD gene in late-onset non-classical isovaleric aciduria. Methods One boy and two girls presented with intractable vomiting were admitted. Urine organic acids and blood acylcarnitines profiles were analyzed. Isovaleric aciduria was diagnosed and confirmed by IVD gene analysis. The patients were treated with leucine-restricted diet and the supplements of L-carnitine and glycine. Results Three patients had recurrent vomiting, drowsiness, odor of sweaty feet and metabolic acidosis from the age of 1 to 2 years. All of them had normal intelligence and leukopenia. One had oligocythemia. The blood isovalerylcarnitines (4.6 to 8.2 μmol/L) and urine isovalerylglycines (36.1 to 1783.56 mmol/mmol creatinine) were elevated. Six mutations were found in their IVD gene. Four mutations (c.157C>T, c.214G>A, c.1183C>G and c.1208A>G) were reported. Two (c.1039G>A and c.1076A>G) were novel. The patients completely recovered after treatment with protein-restricted diet and the supplements of L-carnitine and glycine. Currently, they were aged 19 months to 14 years with normal physical and psychomotor development. Conclusions The clinical features of late-onset non-classical isovaleric aciduria are complex. It is onset in infants and young children and characteristic of recurrent vomiting and metabolic acidosis, which can be diagnosed by the blood acylcarnitine spectrum, urine organic acid analysis, and confirmed by genetic analysis. L-carnitine supplement and diet intervention has significant effects.