Tyrosine hydroxylase deficiency

Title

Other Names:

Parkinsonism, infantile, autosomal recessive; Dystonia, DOPA responsive, autosomal recessive; DOPA responsive dystonia, autosomal recessive; Parkinsonism, infantile, autosomal recessive; Dystonia, DOPA responsive, autosomal recessive; DOPA responsive dystonia, autosomal recessive; Segawa syndrome, autosomal recessive; DYT/PARK-TH; Tyrosine hydroxylase-deficient dopa-responsive dystonia; DYT5b; TH-deficient DRD See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

This disease is grouped under:

Dopa-responsive dystonia

Summary Summary

Tyrosine hydroxylase (TH) deficiency is a rare inherited condition that affects the nervous system. There are three different forms of the condition that vary in severity. The mild form is called TH-deficient dopa-responsive dystonia and typically develops between age twelve months and six years. The two severe forms, which are called infantile parkinsonism and progressive infantile encephalopathy, often begin shortly after birth or during early infancy. Although there is some overlap of features among the three forms, each is associated with unique signs and symptoms. TH deficiency is caused by changes (mutations) in the TH gene and is inherited in an autosomal recessive manner. Affected people are usually treated with levodopa therapy.^[1]^[2]^[3]

Last updated: 2/16/2015

Symptoms Symptoms

There are three different forms of tyrosine hydroxylase (TH) deficiency that vary in severity. The mild form of the condition is called TH-deficient dopa-responsive dystonia. Children affected by this form typically develop features of the condition between age twelve months and six years. Symptoms may include an abnormal gait (manner of walking); lack of coordination when walking or running; repetitive, involuntary movements of the arms and/or legs; unusual positioning of limbs; postural tremor (shaking when holding a position); and abnormal, involuntary eye movements. The features of TH-deficient dopa-responsive dystonia tend to get worse over time but are generally responsive to treatment.^[1]^[3]

The severe form of TH deficiency is called infantile parkinsonism. Children affected by this form generally begin developing features of the condition between age three to twelve months. Signs and symptoms of infantile parkinsonism may include:^[1]^[3]

Delayed motor milestones (i.e. sitting up, crawling, walking)
Intellectual disability
Speech problems
Muscle stiffness, especially in the arms and legs
Unusual positioning of body
Ptosis
Abnormal, involuntary eye movements
Constipation
Gastroesophageal reflux
Difficulty regulating body temperature, blood sugar and blood pressure
Mental health conditions (i.e. depression, anxiety, or obsessive-compulsive behaviors)

The very severe form of TH deficiency which is called progressive infantile encephalopathy, generally develops before age three to six months. Early symptoms may include fetal distress; feeding difficulties; low muscle tone; and small head circumference, height and/or weight from birth. Babies affected by this form generally have severe physical and intellectual disability due to underlying brain dysfunction and structural abnormalities. Other signs and symptoms include severe delay in motor milestones; rigidity and/or spasticity of arms and legs; ptosis of both eye lids; and episodes of profuse sweating, lethargy, irritability and/or excessive drooling.^[2]^[3]

Last updated: 2/16/2015

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.

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Medical Terms	Other Names	Learn More: HPO ID
30%-79% of people have these symptoms
Babinski sign		0003487
Bradykinesia	Slow movements Slowness of movements [ more ]	0002067
Brisk reflexes		0001348
Central hypotonia		0011398
Constipation		0002019
Decreased CSF homovanillic acid		0003785
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
Excessive salivation	Mouth watering Oversalivation Watery mouth [ more ]	0003781
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Focal dystonia		0004373
Gait ataxia	Inability to coordinate movements when walking	0002066
Hypokinesia	Decreased muscle movement Decreased spontaneous movement Decreased spontaneous movements [ more ]	0002375
Irritability	Irritable	0000737
Lethargy		0001254
Limb dystonia		0002451
Lower limb hyperreflexia	Overactive lower leg reflex	0002395
Motor delay		0001270
Myoclonus		0001336
Night sweats		0030166
Oculogyric crisis		0010553
Parkinsonism		0001300
Pes cavus	High-arched foot	0001761
Postural tremor		0002174
Ptosis	Drooping upper eyelid	0000508
Rigidity	Muscle rigidity	0002063
Talipes equinovarus	Club feet Club foot Clubfeet Clubfoot [ more ]	0001762
5%-29% of people have these symptoms
Fever		0001945
Generalized dystonia		0007325
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
1%-4% of people have these symptoms
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Progressive encephalopathy		0002448
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Mask-like facies	Expressionless face Lack of facial expression Mask-like facial appearance [ more ]	0000298
Muscular hypotonia of the trunk	Low muscle tone in trunk	0008936
Parkinsonism with favorable response to dopaminergic medication		0002548
Tremor		0001337
Variable expressivity		0003828

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Tyrosine hydroxylase (TH) deficiency is caused by changes (mutations) in the TH gene. This gene encodes an enzyme that helps convert certain amino acids (building blocks of protein) to dopamine. Dopamine is a chemical that is important to the function of the nervous system. For example, it helps the brain control movement by acting as a messenger to the other parts of the body. Dopamine can also be made into other chemicals that play an important role in the functioning of the autonomic nervous system. Mutations in the TH gene result in reduced levels of dopamine, which leads to the many signs and symptoms associated with TH deficiency.^[1]

Last updated: 2/16/2015

Inheritance Inheritance

Tyrosine hydroxylase deficiency is inherited in an autosomal recessive manner.^[3] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Last updated: 2/16/2015

Diagnosis Diagnosis

A diagnosis of tyrosine hydroxylase (TH) deficiency is typically suspected based on the presence of characteristic signs and symptoms. Analysis of a small sample of cerebrospinal fluid may be recommended to support the diagnosis and to rule out other conditions associated with similar features. Identification of a disease-causing change (mutation) in each copy of the TH gene confirms a diagnosis of TH deficiency.^[2]^[3]

Last updated: 2/16/2015

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.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

People affected by tyrosine hydroxylase (TH) deficiency are generally treated with a medication called levodopa. The effectiveness of levodopa therapy varies significantly depending on the severity of the condition. People affected by the mild form of TH deficiency (TH-deficient dopa-responsive dystonia) generally respond well to treatment. In most cases, this medication is able to drastically improve or even completely alleviate associated symptoms.^[2]^[3]

Unfortunately, children with infantile parkinsonism or progressive infantile encephalopathy (the two severe forms of TH deficiency) may have an incomplete response to levodopa, or it may take several months to several years to see an improvement in symptoms. In many cases, affected children are also extremely sensitive to the drug and may experience negative side affects such as difficulties in performing voluntary movements (dyskinesia), vomiting and appetite suppression of appetite.^[2]^[3]

Last updated: 2/16/2015

Prognosis Prognosis

The long-term outlook (prognosis) for people with tyrosine hydroxylase (TH) deficiency varies based on the severity of the condition. The mild form of TH deficiency (TH-deficient dopa-responsive dystonia) is generally associated with a good prognosis. People affected by this form usually respond quickly and completely to treatment with levodopa, often seeing a full reversal of symptoms.^[1]^[2]^[3]

Unfortunately, babies affected by infantile parkinsonism or progressive infantile encephalopathy generally experience more severe signs and symptoms than those affected by TH-deficient dopa-responsive dystonia. These severe forms of TH deficiency are also more difficult to effectively treat and therefore, tend to have a worse prognosis.^[2]^[3]

Last updated: 2/16/2015

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include different forms of DRD (e.g. autosomal dominant DRD), early onset torsion dystonia, myoclonic dystonia and other types of early-onset parkinsonism. It can also be mistaken for cerebral palsy or spastic paraplegia. Differential diagnoses that need to be considered for the more severe, encephalopathy-like phenotype include febrile infection-related epilepsy syndrome, neonatal hypoxic and ischemic brain injury, other tetrahydrobiopterin (BH4)-related enzyme deficiencies and mitochondrial disorders. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnoses include different forms of DRD (e.g. autosomal dominant DRD), early onset torsion dystonia, myoclonic dystonia and other types of early-onset parkinsonism. It can also be mistaken for cerebral palsy or spastic paraplegia. Differential diagnoses that need to be considered for the more severe, encephalopathy-like phenotype include febrile infection-related epilepsy syndrome, neonatal hypoxic and ischemic brain injury, other tetrahydrobiopterin (BH4)-related enzyme deficiencies and mitochondrial disorders.

Visit the Orphanet disease page for more information.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Dystonia Medical Research Foundation
1 East Wacker Drive
Suite 1730
Chicago, IL 60601-1905
Toll-free: 1-0800-377-3978
Telephone: +1-312-755-0198
Fax: +1-312-803-0138
E-mail: dystonia@dystonia-foundation.org
Website: https://dystonia-foundation.org/
Pediatric Neurotransmitter Disease Association
28 Prescott Place
Old Bethpage, NY 11804
Telephone: 603-733-8409
E-mail: pnd@pndassociation.org
Website: http://www.pndassoc.org/

Do you know of an organization? We want to hear from you.

Learn More 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 Tyrosine hydroxylase deficiency. This website is maintained by the National Library of Medicine.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
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.
PubMed is a searchable database of medical literature and lists journal articles that discuss Tyrosine hydroxylase deficiency. Click on the link to view a sample search on this topic.

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