Laine J, Salo M K, Krogerus L, Kärkkäinen J, Wahlroos O, Holmberg C
Children's Hospital, Helsinki, Finland.
Pediatr Res. 1995 May;37(5):640-5. doi: 10.1203/00006450-199505000-00015.
Type I tyrosinemia (HTI) is an autosomally recessively inherited disease caused by deficiency of fumarylacetoacetate hydrolase. The disease manifests with liver failure, renal tubular defects, and neurologic crises. Currently orthotopic liver transplantation (OLT) enables patients to survive. However, renal fumarylacetoacetate hydrolase deficiency is not corrected by OLT, and the long-term prognosis of the nephropathy is not known. We investigated tyrosine metabolism, GFR, renal tubular function, and histopathology before and 18-36 mo after OLT in eight patients with HTI. Progressive renal dysfunction was not documented despite continuing, although diminished, urinary succinylacetone excretion in all patients. The mean GFR was 82 mL/min/1.73 m2 before and 102 mL at 18 mo and 93 mL at 36 mo after OLT. All patients showed tubular dysfunction before OLT. At 18 mo, glucosuria occurred in one, amino aciduria and phosphaturia in three, and hypercalciuria in six patients. Only hypercalciuria was seen at 36 mo. Renal biopsies showed mild nonspecific changes caused either by minimal progression of the renal disease or by mild cyclosporine nephrotoxicity. In conclusion, patients with HTI had normal GFR, but showed signs of tubular dysfunction 18-36 mo after OLT. Renal function and histopathology should be monitored after OLT for HTI.
I型酪氨酸血症（HTI）是一种常染色体隐性遗传疾病，由富马酰乙酰乙酸水解酶缺乏引起。该疾病表现为肝功能衰竭、肾小管缺陷和神经危机。目前，原位肝移植（OLT）可使患者存活。然而，OLT并不能纠正肾脏富马酰乙酰乙酸水解酶缺乏，且肾病的长期预后尚不清楚。我们对8例HTI患者在OLT术前及术后18 - 36个月进行了酪氨酸代谢、肾小球滤过率（GFR）、肾小管功能和组织病理学研究。尽管所有患者尿中琥珀酰丙酮排泄持续存在（尽管有所减少），但未记录到进行性肾功能不全。OLT术前平均GFR为82 mL/min/1.73 m²，术后18个月为102 mL，36个月为93 mL。所有患者在OLT术前均表现出肾小管功能障碍。18个月时，1例出现糖尿，3例出现氨基酸尿和磷尿，6例出现高钙尿。36个月时仅见高钙尿。肾活检显示，肾病进展轻微或环孢素肾毒性轻微导致轻度非特异性改变。总之，HTI患者GFR正常，但在OLT术后18 - 36个月表现出肾小管功能障碍迹象。OLT术后应对HTI患者的肾功能和组织病理学进行监测。
