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Disease Profile

6-pyruvoyl-tetrahydropterin synthase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

US Estimated

Europe Estimated

Age of onset

Infancy

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ICD-10

E70.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency; Hyperphenylalanemia, BH4-deficient, A; PTS Deficiency

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 13

Definition
6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.

Clinical description
When left untreated, the deficiency causes neurological signs at age 4 or 5 months, although clinical signs are often obvious from birth. The principal symptoms include psychomotor retardation, tonus disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation and difficulty swallowing.

Diagnostic methods
PTPS deficiency should be suspected in all infants with a positive neonatal screening test for phenylketonuria, especially when hyperphenylalaninemia is moderate. The most effective way to diagnose the disorder is to measure pteridine levels in urine and to confirm the result by measuring neurotransmitters 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid and with an oral tetrahydrobiopterin-loading test (20 mg/kg).

Genetic counseling
PTPS deficiency is an autosomal recessive genetic disorder.

Management and treatment
Treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors (L-dopa/carbidopa and 5-hydroxytryptophan).

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Muscular hypotonia
Low or weak muscle tone
0001252
Opisthotonus
0002179
5%-29% of people have these symptoms
Agitation
0000713
Ataxia
0001251
Bradykinesia
Slow movements
Slowness of movements

[ more ]

0002067
Choreoathetosis
0001266
Clonus
0002169
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Depressivity
Depression
0000716
Drowsiness
Sleepy
0002329
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Excessive salivation
Mouth watering
Oversalivation
Watery mouth

[ more ]

0003781
Falls
0002527
Global developmental delay
0001263
Hyperkinetic movements
Muscle spasms
0002487
Hypsarrhythmia
0002521
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Motor delay
0001270
Myoclonus
0001336
Oculogyric crisis
0010553
Pallor
0000980
Poor head control
0002421
Ptosis
Drooping upper eyelid
0000508
Rigidity
Muscle rigidity
0002063
Seizure
0001250
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Dystonia
0001332
Excessive daytime somnolence
Excessive daytime sleepiness
More than typical sleepiness during day

[ more ]

0001262
Hyperphenylalaninemia
0004923
Hyperreflexia
Increased reflexes
0001347
Hypertonia
0001276
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation

[ more ]

0006887
Irritability
Irritable
0000737
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Parkinsonism
0001300
Poor suck
Poor sucking
0002033
Progressive neurologic deterioration
Worsening neurological symptoms
0002344
Psychomotor retardation
0025356
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever

[ more ]

0001954
Small for gestational age
Birth weight less than 10th percentile
Low birth weight

[ more ]

0001518
Tremor
0001337

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on 6-pyruvoyl-tetrahydropterin synthase deficiency. This website is maintained by the National Library of Medicine.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
    Orphanet
    Orphanet
  • PubMed is a searchable database of medical literature and lists journal articles that discuss 6-pyruvoyl-tetrahydropterin synthase deficiency. Click on the link to view a sample search on this topic.