Hereditary Tyrosinemia Type 1 (Hepatorenal Type):
It is autosomal recessive. Fumaryl acetoacetate hydrolase enzyme activity is deficient.
Clinical findings
1. Liver findings: Findings of liver failure, cirrhosis and hepatocellular carcinoma in the later stage (the most common cause of hepatocellular carcinoma from metabolic diseases)
2. Renal findings: Renal tubular dysfunction (Fanconi syndrome) and rickets resistant to vitamin D are seen in the kidney.
3. Polyneuropathy: The increase in succinylacetoacetate causes a defect in porphyrin biosynthesis and acute polyneuropathy mimicking acute intermittent porphyria is seen in 40% of patients. Pain in the legs, extensor hypertonicity in the neck and trunk, paralytic ileus or paralysis leading to respiratory failure in 30% of cases can be seen.
4. Odor: A "rotten cabbage smell" due to methionine metabolites can be heard.
Diagnosis:
• Plasma tyrosine levels and methionine are moderately increased.
• The most important finding of the clinical picture is liver failure, and since tyrosine is one of the amino acids that increase in liver failure, it is not a definitive diagnostic criterion.
• Serum alpha-fetoprotein levels are elevated.
• Definitive diagnosis is made by demonstrating increased succinylacetone in serum and urine.
Treatment:
• Restriction of dietary tyrosine, phenylalanine or methionine is beneficial in some patients and ineffective in others.
• NTBC (nitisinone) is used as medical treatment. The use of nitisinone reduced the need for liver transplantation.
• In cases unresponsive to nitisinone, the treatment is liver transplantation.
Tyrosinemia Type 2 (Richner Hanhart Syndrome)
(Oculocutaneous Tyrosinemia)
• There is liver cytosolic tyrosine aminotransferase deficiency.
• Serum and urine tyrosine levels are very high.
• Eye signs are the first symptom.
• Liver, kidney functions and serum concentrations of other amino acids are normal.
Clinic
• Corneal ulcer: Bilateral herpetic keratitis-like lesions occur.
• Palmar and plantar hyperkeratosis (painful)
• Mild to moderate mental retardation (50%)
• Self mutilation can be seen. This finding is seen together with intermittent ataxia, convulsions and growth retardation in tyrosinemia type 3, which is very rare.
• A diet restricted from tyrosine and phenylalanine is recommended for treatment.
Transient Tyrosinemia of newborns:
• It is seen especially in premature babies due to the delay in the maturation of the 4-OH phenylpyruvic acid dehydrogenase (4-HPPD) enzyme.
• They are caught with a positive Guthrie screening test.
• They are known for having high tyrosine levels as well as phenylalanine levels.
• Blood tyrosine level can be lowered by reducing protein in the diet and giving ascorbic acid.
• It resolves spontaneously within a month.
Hawkinsuria
• It is autosomal dominant.
• Probably 4-HPPD has functional deficiency. The accumulated intermediate metabolites combine with glutathione or cysteine to become hawkinsin.
• Symptoms begin when the infant is weaned and fed with a high protein diet.
• Metabolic acidosis progresses with swimming pool odor in the urine, ketosis, hemolysis, hepatomegaly and growth retardation.
• Response to protein, phenylalanine and tyrosine restricted diet and vitamin C therapy is good.
Alkaptonuria ( Homogentisic Aciduria)
• It is autosomal recessive.
• Homogentisic acid oxidase is deficient and homogentisic acid accumulated in the body is responsible for clinical findings.
• With the accumulation of black polymers of homogentisic acid in cartilage and other mesenchymal tissues rich in connective tissue, blackening of cheek, nose, sclera and ear color is observed (ochronosis).
• Initially, it presents between the ages of 20-40. The most important finding is progressive arthropathies. It causes radiological findings similar to osteoarthritis. Acute exacerbations such as rheumatoid arthritis occur.
• Valve dysfunction and calcifications can be seen in the heart.
Diagnosis
• It is placed with an increase in homogentisic acid excretion in the urine.
• Homogentisic acid and its oxidative products are excreted in the urine. When the patient's urine is kept, the urine color becomes black with the oxidation and polymerization of homogentisic acid and dyes the glands black.
• Patients' urine may turn black with NaOH.
Treatment
• There is no effective treatment for the disease. Symptomatic treatment is given for arthritis. A nitisinone and phenylalanine-tyrosine restricted diet is given, although its long-term efficacy has not been fully demonstrated.