BH4-deficient hyperphenylalaninemia B

Based on the context provided, here is a description of BH4-deficient hyperphenylalaninemia B:

BH4-deficient hyperphenylalaninemia B 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, resulting in hyperphenylalaninemia. The symptoms of BH4-deficient hyperphenylalaninemia B can range from mild to severe and may include:

• Developmental delay
• Intellectual disability
• Movement disorders
• Abnormal muscle tone
• Poor head control
• Seizures

This condition 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 disorder. The symptoms and severity of BH4-deficient hyperphenylalaninemia B can vary depending on the specific genetic mutation involved.

It's worth noting that this is a rare and complex condition, and more research is needed to fully understand its causes and effects.

Based on the context provided, here are some signs and symptoms associated with BH4-deficient hyperphenylalaninemia:

Neurological Symptoms:

1. Abnormal muscle tone
2. Poor head control
3. Seizures
4. Delayed motor development
5. Early onset parkinsonism (in some cases)
6. Oculogyric crises (in some cases)

Other Symptoms:

1. Intellectual disability (if left untreated)
2. Diurnal fluctuation of symptoms (in some cases)

Please note that these symptoms can range from mild to severe and may vary in presentation depending on the individual case.

It's also worth mentioning that BH4-deficient hyperphenylalaninemia is a rare metabolic disorder, and its diagnosis requires specific genetic testing and biochemical analysis.

Diagnostic Tests for BH4-Deficient Hyperphenylalaninemia

BH4-deficient hyperphenylalaninemia is a rare neurometabolic disorder characterized by insufficient synthesis of the monoamine neurotransmitters dopamine and serotonin. Diagnostic tests play a crucial role in confirming the diagnosis of this condition.

• Blood Tests: Blood tests are used to measure the levels of phenylalanine (Phe) and tyrosine (Tyr) in the blood. Elevated Phe levels are a hallmark of BH4-deficient hyperphenylalaninemia [10].
• Urine Tests: Urine tests may also be conducted to measure the levels of Phe and other metabolites.
• DNA Testing: DNA testing is necessary to confirm a diagnosis of a disorder of tetrahydrobiopterin deficiency, including BH4-deficient hyperphenylalaninemia [3]. This test can identify pathogenic variants in genes such as GCH1, PCBD1, PTS, and QDPR.
• BH4 Loading Test: A BH4 loading test may be performed to assess the response of Phe levels to BH4 supplementation. This test is valuable for diagnosing and monitoring patients with various degrees of severity of hyperphenylalaninemia [13].

Other Diagnostic Tools

• Newborn Screening Tests: Abnormal newborn screening tests may also lead to the diagnosis of BH4-deficient hyperphenylalaninemia.
• Clinical Examination: A thorough clinical examination, including a review of medical history and physical symptoms, is essential for diagnosing this condition.

It's worth noting that the diagnostic process for BH4-deficient hyperphenylalaninemia may involve a combination of these tests, and the specific tests used may vary depending on individual circumstances.

Differential Diagnosis of BH4-deficient Hyperphenylalaninemia B

BH4-deficient hyperphenylalaninemia B 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. The differential diagnosis of this condition includes several other disorders that can present with similar symptoms.

Classic Phenylketonuria (PKU)

One of the main differential diagnoses for BH4-deficient hyperphenylalaninemia B is classic PKU, which is caused by a deficiency of the enzyme phenylalanine hydroxylase. This condition can also lead to elevated levels of phenylalanine in the blood and urine.

Hyperphenylalaninemia due to DNAJC12 Deficiency

Another differential diagnosis for BH4-deficient hyperphenylalaninemia B is hyperphenylalaninemia caused by a deficiency of the DNAJC12 gene. This condition can also present with elevated levels of phenylalanine in the blood and urine.

Other Differential Diagnoses

Other conditions that may be considered in the differential diagnosis of BH4-deficient hyperphenylalaninemia B include:

• Tetrahydrobiopterin (BH4) deficiencies: These are a group of disorders characterized by abnormalities in the creation or regeneration of tetrahydrobiopterin, which is essential for the synthesis of dopamine and serotonin.
• GTP-cyclohydrolase I deficiency: This is an autosomal recessive disorder caused by a deficiency of the GTP-cyclohydrolase I enzyme, leading to tetrahydrobiopterin deficiency.

Treatment and Management

The treatment and management of BH4-deficient hyperphenylalaninemia B depend on the underlying cause of the condition. In some cases, sapropterin hydrochloride may be used to treat the condition. It is essential to consider the differential diagnosis for every even slightly elevated blood Phe level, as about 2% of all Phe level elevations detected by newborn screening are due to disorders in BH4 metabolism.

References

• Guide for diagnosis and treatment of hyperphenylalaninemia Pediatr Int. 2021
• Kaufman (1963)
• Danks et al. (1978)