What are the other Names for this Condition? (Also known as/Synonyms)

• BH4-Deficient Hyperphenylalaninemia
• Pterin-4 Alpha-Carbinolamine Dehydratase (PCD) Deficiency Disorder
• Tetrahydrobiopterin-Deficient Hyperphenylalaninemia due to GTP Cyclohydrolase 1 Deficiency

What is Hyperphenylalaninemia due to Dehydratase Deficiency? (Definition/Background Information)

• Hyperphenylalaninemia due to Dehrdatase Deficiency, also known as pterin-4 alpha-carbinolamine dehydratase (PCD) Deficiency Disorder, is considered a transient and benign form of hyperphenylalaninemia due to tetrahydrobiopterin deficiency
• It is characterized by muscular hypotonia, irritability (detected by EEG), slow acquisition of psychomotor skills, age-dependent movement disorders, including dystonia and an accompanying excretion of 7-substituted pterins
• Neurological development is normal with dietary control of blood phenyalanine
• PCD is inherited in an autosomal recessive manner

(Source: Pterin-4 alpha-carbinolamine dehydratase deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Hyperphenylalaninemia due to Dehydratase Deficiency? (Age and Sex Distribution)

• Hyperphenylalaninemia due to Dehydratase Deficiency is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hyperphenylalaninemia due to Dehydratase Deficiency? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hyperphenylalaninemia due to Dehydratase Deficiency can be inherited
• In addition, children of consanguineous parents have an increased risk of being born with the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hyperphenylalaninemia due to Dehydratase Deficiency? (Etiology)

• Hyperphenylalaninemia due to Dehydratase Deficiency is caused by mutation(s) in the PCBD1 gene
• The condition is inherited in an autosomal recessive manner

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Hyperphenylalaninemia due to Dehydratase Deficiency?

The signs and symptoms of Hyperphenylalaninemia due to Dehydratase Deficiency may include:

• Generalized hypotonia
• Hyperphenylalaninemia
• Hypertonia
• Motor delay
• Transient hyperphenylalaninemia
• Tremor

How is Hyperphenylalaninemia due to Dehydratase Deficiency Diagnosed?

Hyperphenylalaninemia due to Dehydratase Deficiency is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hyperphenylalaninemia due to Dehydratase Deficiency?

The complications of Hyperphenylalaninemia due to Dehydratase Deficiency may include:

• Problems with movement
• Delay in reaching development milestones in motor functions
• Development of non-autoimmune diabetes mellitus
• Susceptibility to early-onset type 2 diabetes in adulthood

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hyperphenylalaninemia due to Dehydratase Deficiency Treated?

There is no cure for Hyperphenylalaninemia due to Dehydratase Deficiency, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Hyperphenylalaninemia due to Dehydratase Deficiency be Prevented?

Currently, Hyperphenylalaninemia due to Dehydratase Deficiency may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hyperphenylalaninemia due to Dehydratase Deficiency? (Outcomes/Resolutions)

• The prognosis of Hyperphenylalaninemia due to Dehydratase Deficiency is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hyperphenylalaninemia due to Dehydratase Deficiency:

Hyperphenylalaninemia due to Dehydratase Deficiency is also known by the following names:

• Hyperphenylalaninemia due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency
• Hyperphenylalaninemia with Primapterinuria
• Tetrahydrobiopterin (BH4)-Deficient Hyperphenylalaninemia (HPA) due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency
• Tetrahydrobiopterin-Deficient Hyperphenylalaninemia due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/