van Woerden C S, Groothof J W, Wanders R J A, Waterham H R, Wijburg F R
Academisch Medisch Centrum/Universiteit van Amsterdam, G8-205, Postbus 22.660, 1100 DD Amsterdam.
Ned Tijdschr Geneeskd. 2006 Jul 29;150(30):1669-72.
Primary hyperoxaluria type I (PH1) is a congenital defect in glyoxylate metabolism caused by a deficiency in the liver-specific peroxisomal enzyme known as alanine glyoxylate aminotransferase (AGT). The deficiency is due to mutations in the AGXT gene, located on chromosome 2q37.3, and results in the conversion of glyoxylate to oxalate. The crystallisation of oxalate with calcium results in symptoms varying from a solitary kidney stone to end-stage renal disease with systemic oxalosis. The diagnosis is based on increased oxalate and glycolate excretion in the urine, reduced AGT activity in liver tissue, and confirmed mutations in the AGXT gene. Over 50 disease-causing mutations have been identified in PH1, which are associated with a wide range of effects on the AGT enzyme. Homozygous Gly170Arg or Phei52Ile mutations are associated with a reduction in urinary oxalate excretion upon pyridoxine administration and long-term preservation of renal function when treatment is initiated in a timely manner. Homozygous 33insC and Gly82Arg mutations result in a much poorer prognosis. Mutational analysis of the AGXT gene in PH1 patients can be a useful tool for establishing the diagnosis and choosing an appropriate therapeutic strategy.
I型原发性高草酸尿症（PH1）是一种乙醛酸代谢的先天性缺陷，由肝脏特异性过氧化物酶体酶——丙氨酸乙醛酸转氨酶（AGT）缺乏所致。这种缺乏是由位于2q37.3染色体上的AGXT基因突变引起的，导致乙醛酸转化为草酸。草酸与钙结晶会引发各种症状，从孤立性肾结石到伴有全身性草酸沉着症的终末期肾病不等。诊断基于尿中草酸和乙醇酸排泄增加、肝组织中AGT活性降低以及AGXT基因的确诊突变。在PH1中已鉴定出50多种致病突变，这些突变对AGT酶有广泛影响。纯合子Gly170Arg或Phe152Ile突变与服用吡哆醇后尿草酸排泄减少以及及时开始治疗时肾功能的长期维持有关。纯合子33insC和Gly82Arg突变导致预后差得多。对PH1患者进行AGXT基因突变分析对于确立诊断和选择合适的治疗策略可能是一种有用的工具。
