Current Strategies for the Treatment of Hereditary Tyrosinemia Type I

Abstract

Hereditary tyrosinemia type I (HT-I) is the most common of the three known diseases caused by defects in tyrosine metabolism. This type of tyrosinemia is caused by a mutation in the gene coding for fumarylacetoacetate hydrolase; several mutations in this gene have been identified. The main clinical features of HT-I are caused by hepatic involvement and renal tubular dysfunction. Dietary intervention with restriction of phenylalanine and tyrosine together with supportive measures can ameliorate the symptoms, but given the high risk for hepatocellular carcinoma, a cure for these patients has so far been possible only with liver transplantation. Pharmacologic treatment with nitisinone, a peroral inhibitor of the tyrosine catabolic pathway, offers an improved means of treatment for patients with HT-I. However, longer follow-up periods are needed to establish the role of this drug in ultimately protecting patients from end-stage organ involvement and hepatocellular carcinoma. Experimental work in mice has provided some promise for the future management of tyrosinemia with gene therapy.

Hereditary tyrosinemia type 1 from a single center in Egypt: clinical study of 22 cases

“…Increase of AFP may be a reflection of insufficient metabolic control; however, further examination to exclude hepatocellular carcinoma (HCC) is usually warranted. [20,21] Patients with persistently high levels of AFP are probably at risk of developing cancer as already reported. [22] Another long-term hepatic complication of HT1 is cirrhosis.…”

Neonatal liver failure: aetiologies and management—state of the art

“…This results in accumulation of succinyl acetone, a toxin that damages the liver and kidneys. Dietary intervention with restriction of phenylalanine and tyrosine, together with medication (nitrisinone), helps in biochemical improvement [4]. Long-term surveillance, however, is required as they have a high risk for hepatocellular carcinoma.…”

Recent insights on risk factors of hepatocellular carcinoma

“…Thus, dietary or pharmacological management of hereditary tyrosinemia might offer a strategy for prevention of HCC in these cases [40] . On the other hand, alpha-1-antitrypsin is an acute-phase protein that is produced by liver cells.…”