GLUTARIC ACIDURIA TYPE-I - A COMMON CAUSE OF EPISODIC ENCEPHALOPATHY AND SPASTIC PARALYSIS IN THE AMISH OF LANCASTER COUNTY, PENNSYLVANIA
GLUTARIC ACIDURIA TYPE-I - A COMMON CAUSE OF EPISODIC ENCEPHALOPATHY AND SPASTIC PARALYSIS IN THE AMISH OF LANCASTER COUNTY, PENNSYLVANIA
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DOI：
10.1002/ajmg.1320410122
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发表时间：
1991-10-01
期刊：
影响因子：
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通讯作者：
KELLEY, RI
中科院分区：
文献类型：
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作者：
MORTON, DH;BENNETT, MJ;KELLEY, RI
我们诊断I型谷氨酸尿症（GA-I）在14名儿童从7个旧秩序阿米什家庭在兰开斯特县，宾夕法尼亚州。GA-I是一种罕见的疾病，似乎是阿米什人急性脑病和脑瘫的常见原因。该疾病的自然史，这是以前未认识到在这一人群中，是显着的变化和范围从急性婴儿脑病和猝死静态锥体外系脑瘫正常成人。10名患者在急性传染病发作时在3至18个月之间首次表现出疾病。其中4名儿童在幼儿期死亡，也是死于急性疾病。然而，在存活的儿童中，5岁后神经系统疾病几乎没有进展，并且智力通常得到保留，即使在患有严重痉挛性瘫痪的儿童中也是如此。患者的血浆谷氨酸浓度范围为4.8 - 14.2 μ mol/L（NL 0-5.6 μ mol/L）和尿谷氨酸浓度为12.5 - 196 mg/g肌酸酐（NL 0.5-8.4 mg/g肌酸酐）。我们已经发现，GA-I可以诊断在阿米什人尿谷氨酸浓度的测量，使用同位素稀释气相色谱/质谱法，而诊断很容易错过常规尿有机酸气相色谱法。根据我们对阿米什人GA-Ⅰ自然史的观察，我们预计，通过GC/MS筛查高危个体进行早期诊断，疾病期间限制饮食蛋白和限制蛋白质代谢、脱水和酸中毒的组合将预防患有GA-Ⅰ变体的阿米什人神经系统疾病的发作或进展。
We have diagnosed type I glutaric aciduria (GA-I) in 14 children from 7 Old Order Amish families in Lancaster County, Pennsylvania. An otherwise rare disorder, GA-I appears to be a common cause of acute encephalopathy and cerebral palsy among the Amish. The natural history of the disease, which was previously unreconnized in this population, is remarkably variable and ranges from acute infantile encephalopathy and sudden death to static extrapyramidal cerebral palsy to normal adult. Ten patients first manifested the disease between 3 and 18 months at the time of an acute infectious illness. Four of these children died in early childhood, also during acute illnesses. However, there has been little progression of the neurological disease after age 5 years in the surviving children and intellect usually has been preserved, even in children with severe spastic paralysis.When well, patients have plasma glutaric acid concentrations ranging from 4.8 to 14.2-mu-mol/liter (nl 0-5.6-mu-mol/liter) and urinary glutaric acid concentrations from 12.5 to 196 mg/g creatinine (nl 0.5-8.4 mg/g creatinine). We have found that GA-I can be diagnosed in the Amish by measurement of urinary glutaric acid concentrations using isotope-dilution gas chromatography/mass spectrometry, whereas the diagnosis can easily be missed by routine urine organic acid gas chromatography. Based on our observations about the natural history of GA-I in the Amish, we anticipate that, with early diagnosis afforded by GC/MS screening of individuals at risk, the combination of restriction of dietary protein and limitation of protein catabolism, dehydration, and acidosis during illnesses will prevent the onset or progression of neurological disease in Amish patients with this variant of GA-I.