a condition of faulty metabolism of tyrosine marked by the excretion of unusual amounts of tyrosine in the urine.

1. Tyrosinosis
Dr. V. MAGENDIRA MANI., M.Sc., M.Phil., Ph.D.,TNSET
Assistant Professor of Biochemistry
Islamiah College (Autonomous), Vaniyambadi
magivbio@gmail.com; 9486000227

2. Inborn errors of metabolism
are inherited metabolic disorders that result from defects in genes
coding for specific enzymes. This defect generates abnormal
chemical reactions that disrupt the normal metabolic pathways
resulting in the toxic accumulation of the substrate behind the
block or a deficiency in the product.

3. is a genetic disorder caused by the deficiency of one of the
enzymes required for the multistep process that breaks down
tyrosine.
If untreated, tyrosine and its byproducts build up in tissues and
organs, which leads to serious medical problems.
Tyrosinosis/Tyrosinemia

4. There are three types of tyrosinemia. Each has distinctive
symptoms and is caused by the deficiency of a different enzyme:
Type I tyrosinemia,
the most severe form of this disorder, is caused by a shortage of
the enzyme fumarylacetoacetate hydrolase.
It is also known as hereditary tyrosinemia, hepatorenal
tyrosinemia, FAH deficiency, tyrosinosis and hypertyrosinemia

6. Type II tyrosinemia
It is caused by a deficiency
of the enzyme tyrosine
aminotransferase. This
form of the disorder can
affect the eyes, skin, and
mental development.

7. Type III tyrosinemia is a rare disorder caused by a deficiency of
the enzyme 4-hydroxyphenylpyruvate dioxygenase.
Characteristic features include
Intellectual disability,
Seizures - A seizure is a sudden, uncontrolled electrical disturbance in the
brain. It can cause changes in your behavior, movements or feelings, and in
levels of consciousness
Periodic loss of balance and coordination (intermittent ataxia).
About 10 percent of newborns have temporarily elevated levels of

8. ● but, in these cases, the cause is not genetic.
● The most likely cause is immature liver enzymes due to
premature birth and this condition is essentially benign and
spontaneously disappears with no sequelae.
● Transient tyrosinemia is not categorized as an inborn error of
metabolism because it is not caused by a genetic mutation.

9. EPIDEMIOLOGY
Tyrosinaemia I is much
more common than type II;
Type III is very rare
Worldwide, type I
tyrosinemia affects about 1
person in 100,000.

10. SYMPTOMS
Different babies may have different symptoms
Some may show symptoms within the first few months of life
(acute form); others may develop symptoms around 1 year of
age (chronic form). Some symptoms may be:
Acute form:
★ Poor appetite and failure to grow normally
★ Vomiting
★ Diarrhea, bloody stools
★ Cabbage-like odor
★ Jaundice
★ Hepatomegaly
★ Lethargy - lack of energy

11. Chronic form:
★ Cirrhosis of the liver
★ Pain, numbness, and tingling in parts of the body
★ Kidney problems
★ Episodes of intense abdominal pain
★ Heart muscle weakness
Both forms of tyrosinemia type I may cause liver failure and/or
develop liver cancer

12. DIAGNOSIS
Typical biochemical findings include
● Elevated plasma concentrations of tyrosine, methionine, and
phenylalanine
● Elevated urinary concentration of tyrosine metabolites (p-
hydroxyphenylpyruvate, phydroxyphenyllactate, and p-
hydroxyphenylacetate)
● Decreased fumarylaceteoacetic acid hydrolase (FAH) enzyme
activity

13. THERAPY
★ Nitisinone was approved by the Food and Drug
Administration for treatment of tyrosinemia type I.
★ Nitisinone blocks parahydroxyphenylpyruvic acid
dioxygenase (p-HPPD), the second step in the tyrosine
degradation pathway, and prevents the accumulation of
FAA and its conversion to succinylacetone.
★ Nitisinone should be prescribed as soon as the diagnosis of
tyrosinemia type I is confirmed

14. ★ Low-tyrosine diet to prevent tyrosine crystals from forming in
the cornea.
★ Dietary management should be started immediately upon
diagnosis and should provide a nutritionally complete diet
with controlled intakes of phenylalanine and tyrosine using a
vegetarian diet with low-protein foods.