Hereditary Tyrosinemia Type 1 (HT-1) is an autosomal recessive genetic metabolic condition, one of the rare amino acid disorders typically detected through newborn screening. Affected patients lack the enzyme fumarylacetoacetate hydrolase (FAH), which is necessary to break down the amino acid tyrosine. Failure to properly break down tyrosine leads to abnormal accumulation of tyrosine and its metabolites in the body, without treatment this leads to severe liver disease, amongst other conditions affecting the kidneys and central nervous system.
Early diagnosis, patient counseling and disease management are essential to minimize the risk of potential adverse outcomes.
A positive newborn screen for HT-1 requires confirmatory blood and urine testing. Early symptoms of HT-1, often present in the first month of life, include fever, diarrhea, vomiting, enlarged liver, jaundice and a tendency to bruise easily. Some babies have a distant, cabbage-like odor to their skin and urine. Left untreated, HT-1 can also lead to developmental delays, an enlarged spleen, abdominal edema, and blood clotting abnormalities.
Once the diagnosis is confirmed, extensive counseling and education of parents and caregivers is warranted. Often a multidisciplinary team that includes a pediatrician or other healthcare professional, a metabolic dietician, geneticist and/or social worker provides parents/caregivers with guidance and support.
In addition to a restricted tyrosine and phenylalanine diet, immediate initiation of the patient in nitisinone, such as NITYR tablets, is required without further delay. Nitisinone will help to prevent buildup of dangerous levels of succinylacetone (SA) in the body.
In August 2017, a group of 11 clinical experts in HT-1 including biochemical genetic physicians, metabolic dietitians and clinical psychologists from the US and Canada, came together and published the Diagnosis and treatment of tyrosinemia type 1: a US and Canadian consensus group review and recommendations1. This is a free open-access publication which has become a go-to read for all healthcare professionals involved in the diagnosis and management of patients with HT-1. Access the publication here.
Informing parents/caregivers of an HT-1 diagnosis can be an emotional time. Many will express guilt, shock, disbelief and/or confusion. In our experience, explaining the basics and answering any initial questions is a useful strategy. For example, inform parents/caregivers that HT-1 is a rare genetic disorder that requires a genetic mutation from each parent, and that although it’s a condition that requires a lifelong special diet and medication, their child can still lead a full life.
For more information parents and caregivers can be referred to www.nityr.us as well as relevant patient advocacy groups such as the Tyrosinemia Society www.tyrosinemia.org and the National Organization for Rare Diseases (NORD) www.rarediseases.org.
1 Chinsky, J. et al, Genet Med. 2017 Dec; 19(12).