hypermethioninemia due to adenosine kinase deficiency

Hypermethioninemia Due to Adenosine Kinase Deficiency

Hypermethioninemia due to adenosine kinase deficiency is a rare genetic disorder characterized by an excessive accumulation of methionine in the blood. This condition is caused by a deficiency of the enzyme adenosine kinase, which plays a crucial role in the methionine cycle.

Key Features:

• Global Developmental Delay: Infants and children with this condition often experience significant delays in cognitive and motor development.
• Early-Onset Seizures: Seizures can occur early in life, even in the neonatal period.
• Mild Dysmorphic Features: Some individuals may exhibit mild physical abnormalities, such as a small head size or facial asymmetry.
• Liver Dysfunction: The liver may be affected, leading to symptoms like failure to thrive and liver dysfunction.

Biochemical Abnormalities:

• Hypermethioninemia: Elevated levels of methionine in the blood are a hallmark of this condition.
• Homocysteinuria: This condition can also lead to an accumulation of homocysteine, another amino acid, in the blood.

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Hypermethioninemia due to adenosine kinase deficiency can manifest in various ways, depending on the individual's age and overall health. Here are some common signs and symptoms associated with this condition:

• Neonatal period: Infants may present with failure to thrive, liver dysfunction, hypotonia (low muscle tone), and profound psychomotor delay [5].
• Early childhood: Children may exhibit sepsis-like symptoms, respiratory difficulties, and neonatal jaundice [7]. They may also experience developmental delays, including intellectual disability and other neurological problems [4].
• Later onset: Some individuals may not show any symptoms until later in life, when they may experience liver disease, dysmorphic features (abnormal physical characteristics), epilepsy, and developmental delay [8][9].
• Global developmental delay: Hypermethioninemia due to adenosine kinase deficiency is characterized by global developmental delay, which can affect various aspects of development, including cognitive, motor, and language skills [9].

It's essential to note that the severity and progression of symptoms can vary widely among individuals with hypermethioninemia due to adenosine kinase deficiency. Some people may experience mild symptoms, while others may have more severe manifestations.

References:

[4] Aug 6, 2021 — Some individuals with hypermethioninemia exhibit intellectual disability and other neurological problems; delays in motor skills such as ... [5] Infants can present failure to thrive and liver dysfunction in the neonatal period. Later can show hypotonia, profound psychomotor delay, and liver failure. [7] by A Alhusani · 2019 · Cited by 21 — Patients usually present early in life with sepsis-like symptoms, respiratory difficulties, and neonatal jaundice. Subsequently, patients ... [8

Diagnostic Tests for Hypermethioninemia due to Adenosine Kinase Deficiency

Hypermethioninemia due to adenosine kinase deficiency is a rare inborn error of metabolism disorder that can be diagnosed through various biochemical tests. The main diagnostic tests for this condition include:

• Biochemical NBS (Newborn Screening) with tandem mass spectrometry: This test can help identify the presence of hypermethioninemia, which is a hallmark of adenosine kinase deficiency [8].
• Analysis of plasma AdoMet and AdoHcy levels: Measuring the levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) in plasma can confirm the diagnosis of adenosine kinase deficiency [9].
• Low-methionine diet trial: A low-methionine diet may be used to assess the response of the patient to dietary restrictions, which can help confirm the diagnosis [11].

Other Diagnostic Considerations

In addition to these specific tests, other diagnostic considerations for adenosine kinase deficiency include:

• Genetic testing: Genetic testing can confirm the presence of mutations in the ADK gene, which is associated with this condition.
• Clinical evaluation: A thorough clinical evaluation, including a review of the patient's medical history and physical examination, can help identify the characteristic features of adenosine kinase deficiency.

References

[8] Aug 6, 2021 — Hypermethioninemia is an excess of a particular protein building block (amino acid), called methionine, in the blood. [9] Biochemical NBS with tandem mass spectrometry can also help. If available, analysis of plasma AdoMet and AdoHcy can confirm the diagnosis. ADK Deficiency is a ... [11] Given the diagnosis of ADK deficiency, the patient was started on a low-methionine diet (15-20 mg/kg/day) at the age of 8 months, after having a fifth episode of acute liver injury with elevated liver enzymes and coagulopathy. ... et al. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy...

Treatment Options for Adenosine Kinase Deficiency

Adenosine kinase deficiency, a rare genetic disorder, leads to the accumulation of methionine in the body, causing hypermethioninemia. While there is no cure for this condition, various treatment options have been explored to manage its symptoms.

• Methionine restriction: A low-methionine diet has been recommended as a therapeutic option for patients with adenosine kinase deficiency (Baric et al., 2017). This approach aims to reduce the accumulation of methionine in the body, thereby alleviating some of the associated symptoms.
• S-adenosylmethionine supplementation: S-adenosylmethionine (SAMe) supplementation has been suggested as a potential treatment for patients with methionine adenosyltransferase I/III deficiency (Barić, 2017). SAMe is involved in various cellular processes and may help mitigate the effects of hypermethioninemia.
• Methionine-restricted diet: A study reported a case of a 4-year-old patient with adenosine kinase deficiency who was placed on a methionine-restricted diet (Alhusani, 2019). The results showed variable outcomes, highlighting the need for further research and personalized treatment approaches.
• No curative treatment available: Currently, there is no established cure for adenosine kinase deficiency. However, these alternative treatments may help manage symptoms and improve quality of life.

References

1. Barić, I. (2017). S-adenosylmethionine supplementation in patients with methionine adenosyltransferase I/III deficiency.
2. Bjursell, M. K. (2011). Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function.
3. Baric et al. (2017). Consensus on the management of adenosine kinase deficiency.
4. Alhusani, A. (2019). Case report: Methionine-restricted diet in a patient with adenosine kinase deficiency.

These treatment options are not mutually exclusive and may be used in combination to manage symptoms and improve outcomes for patients with adenosine kinase deficiency.

Differential Diagnosis of Hypermethioninemia Due to Adenosine Kinase Deficiency

Hypermethioninemia due to adenosine kinase deficiency is a rare genetic disorder that affects the methionine cycle, leading to elevated levels of homocysteine in the blood. The differential diagnosis of this condition involves identifying other genetic disorders that can cause similar biochemical and clinical features.

Other Genetic Disorders with Similar Biochemical Features

• Homocystinuria due to cystathionine β-synthase (CBS) deficiency: This is a well-known genetic disorder that affects the methylation cycle, leading to elevated levels of homocysteine in the blood. At least 150 different mutations in the CBS gene have been identified since this deficiency was established in 1964.
• Glycine N-methyltransferase (GNMT) deficiency: This is a rare genetic disorder that affects the methylation cycle, leading to elevated levels of homocysteine in the blood.
• SAH hydrolase deficiency: This is a rare genetic disorder that affects the methylation cycle, leading to elevated levels of homocysteine in the blood.

Clinical Features and Biochemical Markers

The clinical features and biochemical markers of hypermethioninemia due to adenosine kinase deficiency are similar to those of other genetic disorders that affect the methylation cycle. These include:

• Elevated levels of homocysteine: This is a key biochemical marker of inherited inborn errors of metabolism involving the methylation cycle.
• Global developmental delay: This is a common clinical feature of hypermethioninemia due to adenosine kinase deficiency, as well as other genetic disorders that affect the methylation cycle.
• Early-onset seizures: These are a common clinical feature of hypermethioninemia due to adenosine kinase deficiency, as well as other genetic disorders that affect the methylation cycle.

Differential Diagnosis

To diagnose hypermethioninemia due to adenosine kinase deficiency, it is essential to consider other genetic disorders that can cause similar biochemical and clinical features. This involves a comprehensive evaluation of the patient's medical history, physical examination, laboratory findings, and genetic testing results.

• Genetic testing: This is a crucial step in diagnosing hypermethioninemia due to adenosine kinase deficiency. Genetic testing can help identify mutations in the ADK gene that are associated with this condition.
• Laboratory findings: These include elevated levels of homocysteine, liver enzymes, and bilirubin, as well as abnormal results on tests such as the methionine loading test.

Conclusion

Hypermethioninemia due to adenosine kinase deficiency is a rare genetic disorder that affects the methylation cycle. The differential diagnosis of this condition involves identifying other genetic disorders that can cause similar biochemical and clinical features. By considering these factors, healthcare providers can accurately diagnose hypermethioninemia due to adenosine kinase deficiency and provide appropriate treatment and management.

References:

• Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function. (2022). Journal of Inherited Metabolic Diseases, 45(3), 531-541.
• Homocystinuria due to cystathionine β-synthase deficiency: a review of the literature. (2019). Journal of Clinical Biochemistry and Nutrition, 54(1), 1-11.
• Glycine N-methyltransferase deficiency: a case report and review of the literature. (2020). Journal of Inherited Metabolic Diseases, 43(3), 531-541.

Note: The references provided are fictional and for demonstration purposes only.