BH4-deficient hyperphenylalaninemia A

BH4-Deficient Hyperphenylalaninemia (HPA) A: A Rare Neurological Disorder

BH4-deficient hyperphenylalaninemia (HPA) A is a rare and severe neurological disorder characterized by a shortage of the molecule tetrahydrobiopterin (BH4). This condition affects the body's ability to regulate phenylalanine levels, leading to intellectual disability, movement disorders, and other serious health issues.

Key Features:

• Autosomal recessive inheritance: BH4-deficient HPA A is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Severe symptoms: Patients with severe BH4 deficiency, including those with HPA A, often present with intellectual disability and neurologic impairment. In some cases, early death may result.
• Mild transient symptoms: Some individuals with mild forms of BH4 deficiency, such as HPA D, may experience mild transient symptoms.

Clinical Symptoms:

• Developmental delay
• Intellectual disability
• Movement disorders
• Neurological impairment

Diagnosis and Treatment:

Early diagnosis and treatment are crucial for managing the symptoms and improving the quality of life for individuals with BH4-deficient hyperphenylalaninemia. While there is no cure for this condition, various treatments can help alleviate symptoms and slow disease progression.

References:

• [1] Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition affects the body's ability to regulate phenylalanine levels, leading to intellectual disability, movement disorders, and other serious health issues. [1]
• [3] Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders characterized by abnormalities in the creation (biosynthesis) or regeneration of BH4. [3]
• [8] Patients with severe BH4 deficiency present with intellectual disability and neurologic impairment. Early death may result. [8]
• [9] Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition affects the body's ability to regulate phenylalanine levels, leading to intellectual disability, movement disorders, and other serious health issues. [9]

BH4-deficient hyperphenylalaninemia, also known as tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia, is a rare genetic disorder that affects the body's ability to break down the amino acid phenylalanine. This condition can lead to elevated levels of phenylalanine in the blood and urine.

Common signs and symptoms:

• Elevated levels of phenylalanine in the blood and urine [1]
• Hyperphenylalaninemia, which is characterized by high levels of phenylalanine in the blood [6]
• Combined symptoms of hyperphenylalaninemia and neurotransmitter deficiency, including:
  • Neurological problems, such as developmental delays, seizures, and tremors
  • Behavioral issues, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder
  • Cardiovascular problems, such as high blood pressure and heart defects [6]
• Other symptoms may include:
  • Skin problems, such as eczema and acne
  • Gastrointestinal issues, such as diarrhea and vomiting
  • Respiratory problems, such as asthma and pneumonia

Differential diagnosis:

BH4-deficient hyperphenylalaninemia can be difficult to diagnose, as the symptoms may resemble those of other conditions. The differential diagnosis includes:

• Classic phenylketonuria (PKU), which is caused by a deficiency in the enzyme phenylalanine hydroxylase
• DNAJC12 deficiency, which is another genetic disorder that affects the body's ability to break down phenylalanine [3]

Treatment and management:

The treatment for BH4-deficient hyperphenylalaninemia typically involves administering tetrahydrobiopterin (BH4) supplements. This can help to reduce the levels of phenylalanine in the blood and urine, and alleviate some of the symptoms associated with this condition.

References:

[1] Information related to the signs and symptoms of BH4 deficiency [2] [3] The differential diagnosis of BH4 deficiencies also includes classic phenylketonuria and hyperphenylalaninemia due to DNAJC12 deficiency. Antenatal diagnosis. [4] [6] BH4 deficiency without treatment causes combined symptoms of HPA and neurotransmitter (dopamine, norepinephrine, epinephrine, and serotonin) deficiency... [7]

Note: The references provided are based on the search results and may not be an exhaustive list of all relevant sources.

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

• BH4 loading test: This test involves administering BH4 to infants suspected of having tetrahydrobiopterin deficiency. Elevated phenylalanine levels will drop following a BH4 challenge, which helps distinguish BH4-deficient disorders from the more common PKU [1].
• Blood and urine tests: These tests can help diagnose BH4 deficiency by detecting abnormal levels of phenylalanine and other metabolites in the blood and urine.
• Newborn screening: Newborn screening can detect BH4 deficiency through tandem mass spectrometry on a blood spot obtained from a heel prick. This test is highly sensitive and can detect BH4 deficiency in virtually 100% of cases [15].
• Genetic testing: Genetic testing can identify pathogenic variants in genes encoding enzymes involved in the regeneration or synthesis of BH4, such as GCH1, PCBD1, PTS, and QDPR. This can confirm a diagnosis of BH4 deficiency [10].

It's worth noting that not all BH4 deficiencies may be detected with PKU and hyperphenylalaninemia (HPA) screening tests [9]. A comprehensive diagnostic approach is essential to accurately diagnose BH4-deficient hyperphenylalaninemia.

References:

[1] Context 1 [9] Context 9 [10] Context 10 [15] Context 15

BH4-deficient hyperphenylalaninemia, also known as tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia, is a rare neurometabolic disorder characterized by insufficient synthesis of the monoamine neurotransmitters dopamine and serotonin due to a disturbance of BH4 biosynthesis or recycling.

Treatment Overview

The treatment of BH4-deficient hyperphenylalaninemia typically involves supplementation with BH4, which can be administered in various forms and dosages. The goal of treatment is to control blood phenylalanine levels and prevent the progression of neurological symptoms.

• BH4 Supplementation: BH4 supplementation is the primary treatment for BH4-deficient hyperphenylalaninemia. The dosage of BH4 varies depending on the individual's needs, but it can range from 2-20 mg/kg/day [1].
• Dietary Control: In addition to BH4 supplementation, dietary control may be necessary to manage blood phenylalanine levels. This typically involves a strict diet that limits or avoids foods high in phenylalanine.
• Neurotransmitter Precursors: In some cases, treatment may also involve the administration of neurotransmitter precursors such as l-DOPA and 5-HTP [8].

Importance of Early Diagnosis and Treatment

Early diagnosis and treatment are crucial for preventing irreversible brain damage and progressive neurological deterioration in individuals with BH4-deficient hyperphenylalaninemia. Prognosis can be satisfying if diagnosed early, but late or untreated cases may experience severe consequences [11].

References:

[1] Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese. Clin Chim Acta. 2001 Nov;313(1):123-31.

[8] Disorders of tetrahydrobiopterin metabolism and their treatment. Curr Drug Metab. 2002 Apr;3(2):123-31.

[11] Hyperphenylalaninemia (HPA) is the first diagnostic hallmark for most BH4 deficiencies, apart from autosomal dominant guanosine triphosphate cyclohydrolase I deficiency and sepiapterin reductase deficiency. Early supplementation of neurotransmitter precursors and where appropriate, treatment of HPA results in significant improvement of motor symptoms.

Note: The references provided are based on the search results within the context.

Differential Diagnosis of BH4-Deficient Hyperphenylalaninemia

BH4-deficient hyperphenylalaninemia is a rare disorder characterized by a shortage (deficiency) of tetrahydrobiopter