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4-Hydroxyphenylpyruvate dioxygenase deficiency(TYRSN3)

MedGen UID:
78694
Concept ID:
C0268623
Disease or Syndrome
Synonyms: 4-alpha hydroxyphenylpyruvate dioxygenase deficiency; 4-alpha hydroxyphenylpyruvic acid oxidase deficiency; 4-HYDROXYPHENYLPYRUVIC ACID OXIDASE DEFICIENCY; Tyrosinemia type 3; Tyrosinemia Type III; TYRSN3
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: 4-Hydroxyphenylpyruvate dioxygenase deficiency (413356003); Tyrosinemia type III (415764005); 4-Hydroxyphenylpyruvate hydroxylase deficiency (413356003); Tyrosinemia type 3 (415764005)
 
Gene (location): HPD (12q24.31)
OMIM®: 276710
Orphanet: ORPHA69723

Definition

Tyrosinemia type III is an autosomal recessive disorder caused by a deficiency in the activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) and is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into urine. Patients with this disorder have mild mental retardation and/or convulsions, with the absence of liver damage (summary by Tomoeda et al., 2000). [from OMIM]

Additional description

From GHR
Tyrosinemia is a genetic disorder characterized by disruptions in the multistep process that breaks down the amino acid tyrosine, a building block of most proteins. If untreated, tyrosine and its byproducts build up in tissues and organs, which can lead to serious health problems.There are three types of tyrosinemia, which are each distinguished by their symptoms and genetic cause. Tyrosinemia type I, the most severe form of this disorder, is characterized by signs and symptoms that begin in the first few months of life. Affected infants fail to gain weight and grow at the expected rate (failure to thrive) due to poor food tolerance because high-protein foods lead to diarrhea and vomiting. Affected infants may also have yellowing of the skin and whites of the eyes (jaundice), a cabbage-like odor, and an increased tendency to bleed (particularly nosebleeds). Tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones (rickets), and an increased risk of liver cancer (hepatocellular carcinoma). Some affected children have repeated neurologic crises that consist of changes in mental state, reduced sensation in the arms and legs (peripheral neuropathy), abdominal pain, and respiratory failure. These crises can last from 1 to 7 days. Untreated, children with tyrosinemia type I often do not survive past the age of 10.Tyrosinemia type II can affect the eyes, skin, and mental development. Signs and symptoms often begin in early childhood and include eye pain and redness, excessive tearing, abnormal sensitivity to light (photophobia), and thick, painful skin on the palms of their hands and soles of their feet (palmoplantar hyperkeratosis). About 50 percent of individuals with tyrosinemia type II have some degree of intellectual disability.Tyrosinemia type III is the rarest of the three types. The characteristic features of this type include intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia).About 10 percent of newborns have temporarily elevated levels of tyrosine (transient tyrosinemia). In these cases, the cause is not genetic. The most likely causes are vitamin C deficiency or immature liver enzymes due to premature birth.  https://ghr.nlm.nih.gov/condition/tyrosinemia

Clinical features

Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
4-Hydroxyphenylpyruvic aciduria
MedGen UID:
376416
Concept ID:
C1848678
Finding
Increased concentration of pyruvic acid in the urine.
4-Hydroxyphenylacetic aciduria
MedGen UID:
376417
Concept ID:
C1848680
Finding
Increased concentration of 4-hydroxyphenylacetic acid in the urine.
Hypertyrosinemia
MedGen UID:
742296
Concept ID:
C1879362
Disease or Syndrome
An increased concentration of tyrosine in the blood.
Abnormality of the liver
MedGen UID:
893061
Concept ID:
C4021780
Finding
An abnormality of the liver.
Elevated hepatic transaminases
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
The following clinical feature is unrelated to 4-Hydroxyphenylpyruvate dioxygenase deficiency

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGV4-Hydroxyphenylpyruvate dioxygenase deficiency
Follow this link to review classifications for 4-Hydroxyphenylpyruvate dioxygenase deficiency in Orphanet.

Recent clinical studies

Etiology

Cerone R, Holme E, Schiaffino MC, Caruso U, Maritano L, Romano C
Acta Paediatr 1997 Sep;86(9):1013-5. PMID: 9343288

Diagnosis

Kitagawa T
Proc Jpn Acad Ser B Phys Biol Sci 2012;88(5):192-200. PMID: 22687740Free PMC Article
Cerone R, Holme E, Schiaffino MC, Caruso U, Maritano L, Romano C
Acta Paediatr 1997 Sep;86(9):1013-5. PMID: 9343288

Therapy

Cerone R, Holme E, Schiaffino MC, Caruso U, Maritano L, Romano C
Acta Paediatr 1997 Sep;86(9):1013-5. PMID: 9343288

Prognosis

Kitagawa T
Proc Jpn Acad Ser B Phys Biol Sci 2012;88(5):192-200. PMID: 22687740Free PMC Article
Cerone R, Holme E, Schiaffino MC, Caruso U, Maritano L, Romano C
Acta Paediatr 1997 Sep;86(9):1013-5. PMID: 9343288

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