Diagnosis of Hereditary tyrosinemia type 1

Diagnosis of Hereditary tyrosinemia type 1
Zahra Beyzaei,^1,* Pardis Askarizadeh,² Farzaneh Farazi,³
1. Zand Institute of higher education, Shiraz, Iran
2. Zand Institute of higher education, Shiraz, Iran
3. Zand Institute of higher education, Shiraz, Iran
Introduction: Tyrosinemia type 1 (HT1) also known as fumarylacetoacetase deficiency (EC: 3.7.1.2), is a rare inherited autosomal recessive disease that results from a disturbance in the metabolism of an amino acid. The disease is caused by defective activity of the enzyme fumarylacetoacetate hydrolase (FAH), which catalyzes the final stage of tyrosine catabolism; Leads to the accumulation of toxic metabolites. Early diagnosis is essential because early medical management, which includes restricting the diet rich in phenylalanine and tyrosine, prevents the accumulation of toxic metabolites, and prevents the development of chronic liver disease, tubular kidney damage, and liver cancer. Symptoms occur at different times depending on the type of disease. It may occur in the acute form of the disease during the first few months, in the semi-acute form in the second half of the first year, or in the chronic form in later years to adulthood.
Methods: We conducted searches in the following electronic databases: Pubmed, Embase, Web of Science, and google scholar. We searched using text word and MeSH terms relating to “Tyrosinemia type 1 OR inborn errors of metabolism”, AND “succinylacetone OR DBS”. The search was conducted on 26th January 2019 without any restriction in time and language. We examined reference lists of included studies and previous reviews.
Results: Although there are many causes of tyrosinemia, hereditary tyrosinemia can be diagnosed from clinical symptoms and biochemical analysis. Diagnosis of tyrosinemia type I would be based on examination of urinary organic acids. The level of succinylacetone in the serum of infected people is excreted in the urine, which is the basis for the diagnosis of hereditary tyrosinemia type I. Excretion of succinyl acetone in the urine causes the urine to smell like cooked cabbage or rotten mushrooms. Other way to diagnosis is plasma amino acids measurement which detected by high/or normal tyrosine level and increased methionine. In addition, Urine porphyrins is other diagnosis method. Delta aminolevulinic acid (due to inhibition of delta aminolevulinic hydrate by enzyme succinyl acetone) was increased in the patients. The best method to detect tyrosinemia is measuring of Succinylaceton (SA) in blood and urine. Succinyl acetone enters the mitochondria of renal lymph nodes and inhibits the Krebs cycle of aminolevulinic acid hydrate (which is also a precursor to synthesis) and increases tubular damage.Screening for tyrosinemia type1 using burst mass spectrometry measurements of SA from dry bloodstains seems promising. NBS using MS/MS detection of SA in bloodstains is the best current method for early detection of HT-1. After a positive NBS result, it is best to repeat the SA test with a new urine sample as soon as possible; Also perform tests such as liver function tests (PT, aPTT, aspartate transaminase or alanine transaminase), AFP, PAA, electrolyte and glucose. If HT-1 is highly suspected, plasma amino acids (PAA) and liver function tests such as prothrombin time (PT),(INR), partial thromboplastin time (PTT), and α-fetoprotein(AFP) should be evaluated at the first examination. Nowadays, molecular tests is one of the best method to diagnose genetic disorders. Analysis of FAH gene mutation is one of the best choice for patients. More than 100 mutations in the gene encoding fumaryl acetate hydrolase (FAH) cause type 1 hereditary tyrosinemia (HT-1). Some known mutations reduce the catalytic activity of FAH. The use of blood SA as an NBS marker is expected to detect all infants with HT-1. Most of these babies with HT-1 can live a life without liver or kidney disease if they are properly diagnosed and medically treated. After confirmation of the diagnosis, NTBC and diet treatment should be started immediately.
Conclusion: Tyrosinemia type 1 is an autosomal recessive disease; diagnosis of this disease can be done before or after birth by genetic testing and amniotic fluid testing, neonatal screening tests, plasma SA levels, plasma amino acid levels and liver tests. Early diagnosis with medical management can reduce the symptoms and complications of the disease. Readily available diagnostic tests are too insensitive to distinguish between these variants, and more definitive but technically difficult tests can be performed rapidly in only a few centers. Therefore, effective management may be compromised, due to the inability of obtaining a working diagnosis quickly.
Keywords: Tyrosinemia; inborn errors; Diagnosis; Newborn screening