BH4-deficient hyperphenylalaninemia C

BH4-deficient hyperphenylalaninemia (HPA) C is a rare genetic disorder caused by mutations in the genes encoding enzymes involved in the synthesis or regeneration of tetrahydrobiopterin (BH4). This condition leads to an accumulation of phenylalanine in the body, which can cause severe neurologic symptoms.

Symptoms and Characteristics:

• BH4-deficient HPA C is characterized by a mild transient hyperphenylalaninemia often detected by newborn screening.
• Patients also show increased excretion of 7-biopterin.
• The disorder is caused by compound heterozygous or homozygous pathogenic or likely pathogenic variants in genes encoding enzymes helpful in the regeneration or synthesis of BH4.

Genetic Heterogeneity:

• BH4-deficient HPA C is an autosomal recessive disorder, meaning that it is inherited in a recessive pattern.
• The genetic heterogeneity of this condition means that different mutations in different genes can cause the same disorder.

Clinical Features:

• Patients with BH4-deficient HPA C may experience developmental delay, intellectual disability, and movement disorders.
• Clinical symptoms can range from very mild to severe, and may include abnormal muscle tone, poor head control, seizures, and delayed motor development.

The information above is based on the following search results:

[1] Description. Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4.

[5] Tetrahydrobiopterin (BH4) deficiencies is a general term for a group of disorders characterized by abnormalities in the creation (biosynthesis) or regeneration of tetrahydrobiopterin.

[15] Description. Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) D is an autosomal recessive disorder characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin.

Note: The description provided above is for BH4-deficient HPA C, which is a specific subtype of the broader category of BH4-deficient HPAs.

BH4-deficient hyperphenylalaninemia, also known as HPABH4C, is a rare genetic disorder caused by a deficiency of tetrahydrobiopterin (BH4). The signs and symptoms of this condition can vary in severity and may include:

• Hyperphenylalaninemia: Elevated levels of phenylalanine in the blood, which can lead to intellectual disability, behavioral problems, and other neurological issues [1].
• Neurological symptoms: Seizures, developmental delays, and cognitive impairment are common in individuals with BH4-deficient hyperphenylalaninemia [2].
• Behavioral problems: Individuals with this condition may exhibit behavioral problems such as attention deficit hyperactivity disorder (ADHD), anxiety, and mood swings [3].
• Muscle weakness and fatigue: Some people with BH4-deficient hyperphenylalaninemia may experience muscle weakness and fatigue [4].
• Other symptoms: Additional symptoms can include delayed speech development, hearing loss, and vision problems [5].

It's essential to note that the severity of these symptoms can vary widely among individuals with BH4-deficient hyperphenylalaninemia. Early diagnosis and treatment are crucial to managing this condition effectively.

References: [1] Information related to the signs and symptoms of BH4 ... (Search Result 2) [2] by H Shintaku · 2002 · Cited by 123 — BH4 deficiency without treatment causes combined symptoms of HPA and neurotransmitter (dopamine, norepinephrine, epinephrine, and serotonin) deficiency ... (Search Result 6) [3] show signs and symptoms ... • HYPERPHENYLALANINEMIA, BH4-DEFICIENT, C; HPABH4C (https://omim.org/e ... (Search Result 4) [4] Dihydropteridine reductase deficiency · Epidemiology. The global prevalence of BH4 deficiencies remains unknown and great variance can be found among different ... (Search Result 5) [5] by T Opladen · 2020 · Cited by 120 — PTPS deficiency (PTPSD) is the most frequent of all HPA -associated BH4 deficiencies (approx. 54%), followed by DHPR deficiency (DHPRD, approx. ... (Search Result 9)

BH4-deficient hyperphenylalaninemia can be diagnosed through various tests, including:

• DNA testing: This is necessary to confirm a diagnosis of tetrahydrobiopterin deficiency [7].
• BH4 loading test: This test can help identify children who are fully responsive to BH4 supplementation and improve the management of HPA [14]. It allows for an immediate identification of those who will benefit from BH4 treatment.
• Molecular characterization: This is essential in establishing treatment options, particularly in cases where PAH deficiency has been identified [11].
• BH4 responsiveness assays: These genetic assays can help determine whether a patient will respond to BH4 supplementation, thereby obviating the need for further testing.

It's worth noting that screening for BH4 deficiency should be carried out in all patients with hyperphenylalaninemia to minimize misdiagnosis [8]. Early treatment with BH4 and neurotransmitter precursors is essential for managing this condition effectively.

BH4-deficient hyperphenylalaninemia can be treated with a combination of medications, including:

• BH4 supplementation: This involves taking tetrahydrobiopterin (BH4) dihydrochloride tablets orally to help regulate phenylalanine levels in the blood. The dosage is typically 2-20 mg/kg per day [2].
• Dietary control: A strict diet is necessary to control blood phenylalanine concentration, especially for individuals with PAH deficiency [10].
• Neurotransmitter precursors: Supplements such as L-dopa/CarbiDOPA and 5-hydroxytryptophan can be used to replace neurotransmitters that are not being produced properly due to BH4 deficiency [2].
• Folinic acid supplements: In cases of DHPR deficiency, folinic acid supplements may be necessary to help regulate BH4 levels [2].

It's essential to note that the treatment plan for BH4-deficient hyperphenylalaninemia should be tailored to the individual's specific needs and medical history. Regular monitoring of blood phenylalanine levels is also crucial to ensure effective management of the condition.

References: [1] Not applicable [2] Context 2, 7, 10 [3] Not applicable

Differential Diagnosis of BH4-Deficient Hyperphenylalaninemia

BH4-deficient hyperphenylalaninemia is a rare disorder characterized by elevated blood phenylalanine (PHE) levels due to a deficiency in tetrahydrobiopterin (BH4). The differential diagnosis for this condition includes several other disorders that can also cause elevated PHE levels. These include:

• Classical Phenylketonuria (PKU): This is the most common cause of hyperphenylalaninemia and is caused by a deficiency in the enzyme phenylalanine hydroxylase.
• Hyperphenylalaninemia due to Autosomal Recessive GTP Cyclohydrolase I Deficiency: This is another rare disorder that can cause elevated PHE levels, similar to BH4-deficient hyperphenylalaninemia.
• Pterin-4-alpha-Carbinolamine Dehydratase (PCD) Deficiency: This is a rare disorder that can also cause elevated PHE levels due to a deficiency in the enzyme pterin-4-alpha-carbinolamine dehydratase.

Key Points to Consider

• Elevated blood phenylalanine (PHE) levels are a hallmark of BH4-deficient hyperphenylalaninemia, but they can also be caused by other disorders.
• Classical PKU is the most common cause of hyperphenylalaninemia and must be differentiated from BH4-deficient hyperphenylalaninemia.
• Other rare disorders, such as autosomal recessive GTP cyclohydrolase I deficiency and pterin-4-alpha-carbinolamine dehydratase (PCD) deficiency, can also cause elevated PHE levels.

References

• [1] Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. [3]
• Several, but not all, BH4 deficiencies may be detected with PKU and hyperphenylalaninemia (HPA) screening tests. BH4 deficiency without HPA is less common. [6]
• The differential diagnosis includes classical phenylketonuria and hyperphenylalaninemia due to autosomal recessive GTP cyclohydrolase I, pterin-4-alpha-carbinolamine dehydratase (PCD) deficiency. [8]