Different genotypes in a large Italian family with recurrent hereditary fructose intolerance
Different genotypes in a large Italian family with recurrent hereditary fructose intolerance
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DOI：
10.1097/meg.0b013e3282f172e6
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发表时间：
2008-02-01
影响因子：
2.1
通讯作者：
Morrone, Amelia
中科院分区：
文献类型：
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作者：
Caciotti, Anna;Donati, Maria Alice;Morrone, Amelia
目的遗传性果糖不耐受是由肝脏、小肠和肾脏中表达的醛缩酶B酶缺乏所致。患者通常表现出对水果和糖果的明显厌恶；然而，如果没有诊断出来，持续或偶然摄入果糖可能是致命的。本文旨在改善这些患者的临床和分子特征，以避免危险的误诊。方法我们报道了一个意大利队列中的分子结果：aidolase B突变的发生，特别是一个反复遗传性果糖耐量异常大家族的临床和分子特征。结果我们队列中的患者显示了三种最常见的突变(p.A150P、p.A175D和p.N335K)。这种分子检测足以覆盖在我们的患者中发现的遗传性果糖不耐受的所有突变等位基因。遗传性果糖不耐受突变的等位基因频率分别为：p.A150P为69.2%，p.A175D为23.1%，p.N335K为77%。复发家系的先证者是已知的醛缩酶B基因p.A150P和p.A175D突变等位基因的杂合子。高危家庭成员的分子特征也发现了p.N335K突变。此外，年龄最大的患者表现出轻微的临床损害。结论我们的结果表明，遗传性果糖不耐受的诊断可能会因临床和遗传家庭内变异而复杂化。因此，了解每个家庭成员的临床和地理病史对于减少潜在的致命误诊和便利这类患者接受适当的遗传咨询至关重要。
Objectives Hereditary fructose intolerance is caused by a deficiency of the aldolase B enzyme, which is expressed in the liver, small intestine and kidneys. Patients usually show a marked aversion to fruits and sweets; if, however, it is not diagnosed, persistent or incidental ingestion of fructose might be lethal. Our paper aims at improving the clinical and molecular characterizations of these patients, to avoid dangerous misdiagnoses.Methods Here we report the molecular results in an Italian cohort: on the occurrence of aidolase B mutations and, in particular, on the clinical and molecular characterization of a large family with recurrent hereditary fructose intolerance.Results Patients included in our cohort showed the three most common mutations (p.A150P, p.A175D and p.N335K). Such molecular tests were enough to cover all the mutated alleles of hereditary fructose intolerance found in our patients. The allele frequencies of hereditary fructose intolerance mutations detected were 69.2% for p.A150P, 23.1% for p.A175D and 77% for p.N335K. The proband of the family with recurrence of the disease was heterozygous for the known p.A150P and p.A175D mutated alleles of the aldolase B gene. Molecular characterization of at-risk family members also identified the p.N335K mutation. In addition, the oldest affected patients exhibited mild clinical impairment.Conclusions Our results indicate that the diagnosis of hereditary fructose intolerance can be complicated by clinical and genetic intrafamilial variability. A knowledge of the clinical and geographical history of each family member is thus essential, to reduce potentially lethal misdiagnoses and to facilitate such patients to receive appropriate genetic counselling.