Tyrosinemia Type 1: An Overview of Nursing Care

Elizabeth Barnby, DNP, ACNP-BC, RN

Disclosures

Pediatr Nurs. 2014;40(2):61-66. 

In This Article

Pathophysiology

TT1 is characterized by the child's inability to break down tyrosine. Tyrosine is an essential amino acid contained in protein that the body needs to perform cellular functions. Normally, the enzyme fumarylacetoacetate hydrolase (FAH) catalyzes tyrosine, but children with TT1 have a deficiency of this essential enzyme. The deficiency is caused by a mutation on chromosome 15q23–25 (Nyhan, Barshop, & Ozand, 2005; Paradis, 1996). The disease is an autosomal recessive disorder that is expressed when a child receives the trait or mutation from both parents. In the carrier state, the mutation is harmless but can be passed on to offspring.

An interruption in the tyrosine catabolic pathway causes a metabolic gridlock in the human body with toxic substances accumulating in tissues throughout the body. Treatment can prevent the accumulation of these toxic substances. The combination of improvements in newborn screening and pharmacotherapy has improved outcomes (Nobili et al., 2010).

The FAH enzyme at the terminal end of the tyrosine catabolic pathway is crucial to the breakdown of tyrosine. When it is absent, toxic metabolites higher up the pathway accumulate and cause disease (Scott, King, & Trahms, 2008). Occasionally, a spontaneous mutation can occur that produces pockets of normal enzyme activity, and this produces variable phenotypic expression (Nakamura, Tanaka, Mitsubuchi, & Endo, 2007). Because phenotypic expression varies, two children with the exact same chromosomal mutation can have varying degrees of disease severity.

FAH deficiency leads to an accumulation of fumarylacetoacetate, maleylacetoacetate, succinylacetoacetone, and succinylacetone. Maleylacetoacetate causes renal tubular dysfunction in a Fanconi-like syndrome of renal failure and vitamin D-resistant rickets (Jacobs, van Beurden, Klomp, Berger, & van den Berg, 2006). Fumarylacetoacetate and maleylacetoacetate cause hepatocyte injury that can result in end stage liver disease, bleeding, and hepatocellular carcinoma (Orejuela, Jorquera, Bergeron, Finegold, & Tanguay, 2008). Succinylacetone is an inhibitor of the heme synthesis pathway, causing neurotoxicity that is similar to lead poisoning or aminolevulinic acid dehydratase (ALAD) deficiency porphyria (Wyllie & Hyams, 2006). The neurotoxicity can cause muscle paralysis and respiratory arrest (Krous, 2010; Turgeon et al., 2008).

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