hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

Hypermethioninemia with Deficiency of S-adenosylhomocysteine Hydrolase

Hypermethioninemia is a condition characterized by an excess of the amino acid methionine in the blood. This can occur when methionine is not broken down properly in the body, leading to its accumulation.

Causes and Inheritance Pattern

The deficiency of S-adenosylhomocysteine hydrolase (SAHH) enzyme is a rare genetic disorder that causes hypermethioninemia. This condition is inherited in an autosomal recessive pattern, meaning that both parents must be carriers of the mutated gene for their child to inherit the condition.

Symptoms and Effects

The symptoms of hypermethioninemia due to SAHH deficiency can vary, but they often include:

• Psychomotor delay: Delayed development of motor skills and coordination
• Behavioral disorders: Abnormal behavior, such as agitation or aggression
• Severe myopathy: Muscle weakness and wasting
• Delayed myelination: Slowed development of the nervous system

Impact on Muscles, Liver, and Nervous System

The SAHH deficiency affects not only the muscles but also the liver and nervous system. The condition can lead to death in infancy if left untreated.

References

• [1] Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive severe neurometabolic disorder affecting the muscles, liver, and nervous system, resulting in death in infancy (summary by Bas et al., 2020).
• [10] Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency (SAHH deficiency) is a muscle disease associated with high blood levels of methionine and creatine kinase (CK).

Signs and Symptoms of Hypermethioninemia with Deficiency of S-adenosylhomocysteine Hydrolase

Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase is a severe neurometabolic disorder that affects the muscles, liver, and brain. The signs and symptoms of this condition can vary in severity and may include:

• Developmental delays: Delays in motor skills such as standing or walking [9]
• Sleeping longer or more often (lethargy): Infants with hypermethioninemia may sleep for longer periods than usual, which is a common sign of the condition [7], [8], [10]
• Weak muscle tone (hypotonia): Weakness in muscles, which can lead to delays in motor skills development [9], [10]
• A "cabbage-like" smell: A distinctive odor that may be present due to the buildup of methionine in the body [7], [8], [10]
• Liver enzyme elevation (hepatic transaminase): Elevated liver enzymes, which can indicate liver damage or dysfunction [3]
• Raised blood homocysteine: High levels of homocysteine in the blood, which is a marker for this condition [3]
• Low blood albumin: Low levels of albumin in the blood, which can be associated with liver disease and malnutrition [3]

It's essential to note that these symptoms may not be present in all individuals with hypermethioninemia, and the severity of the condition can vary widely. If you suspect that someone has this condition, it's crucial to consult a medical professional for proper diagnosis and treatment.

References: [1] Context result 4 [2] Context result 5 [3] Context result 3 [7] Context result 6 [8] Context result 7 [9] Context result 9 [10] Context result 10

Diagnostic Tests for Hypermethioninemia with Deficiency of S-adenosylhomocysteine Hydrolase

Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase can be diagnosed through various laboratory tests. The following are some of the diagnostic tests that may be used to confirm this condition:

• Complete Blood Count (CBC): A CBC is a blood test that measures the levels of different cells in the blood, including red and white blood cells, platelets, and hemoglobin.
• Basic Urine and Sediment Tests: These tests are used to detect abnormalities in the urine, such as proteinuria or hematuria.
• Screening for Duchenne Muscular Dystrophy: This test is used to rule out other conditions that may cause similar symptoms.
• **Plasma S-adenosylmethionine (SAM

Treatment Options for Hypermethioninemia with Deficiency of S-adenosylhomocysteine Hydrolase

According to the available information, there are several treatment options that may be beneficial for individuals with hypermethioninemia due to deficiency of S-adenosylhomocysteine hydrolase.

• S-adenosylmethionine (SAM) supplementation: SAM supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency, which is related to the condition [1]. However, it's essential to note that this information might not directly apply to S-adenosylhomocysteine hydrolase deficiency.
• Low-methionine diet: A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L [11]. There is some evidence that this diet may also be beneficial in patients with S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies.
• Cystine supplementation: Patients with GNMT-related hypermethioninemia may benefit from a low methionine diet and cystine supplementation [4].
• Dietary restriction of methionine: Dietary restriction of methionine demonstrates clinical benefits in some affected patients and should be trialed in patients with SAH hydrolase deficiency [7].

It's essential to consult with a healthcare professional for personalized advice on the most suitable treatment plan. They can help determine the best course of action based on individual circumstances.

References:

[1] Barić, I. (2017). S-adenosylmethionine supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency. [4] Barić, I. (2004). In parallel, to compensate for inhibition of methyltransferases, supplemental phosphatidylcholine was provided mainly as two half egg yolks per day. [7] Huang, Y. (2022). Dietary restriction of methionine demonstrates clinical benefits in some affected patients and should be trialed in patients with SAH hydrolase deficiency. [11] A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L.

Differential Diagnosis of Hypermethioninemia with Deficiency of S-adenosylhomocysteine Hydrolase

Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency has a very wide differential diagnosis, making it essential to consider various conditions when diagnosing this disorder. Some of the key differential diagnoses include:

• Chronic myopathies: These are a group of muscle disorders that can cause progressive muscle weakness and wasting [2].
• Muscular dystrophies: A genetic disorder characterized by progressive muscle degeneration and weakness [2].
• Floppy infant syndrome: A condition characterized by muscle weakness, floppiness, and poor muscle tone in infants [2].

Other conditions that may be considered as differential diagnoses for hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency include:

• Metabolic disorders: Such as maple syrup urine disease, phenylketonuria, and other amino acid metabolism disorders.
• Neurological disorders: Such as cerebral palsy, epilepsy, and other conditions affecting the nervous system.

It is essential to note that a comprehensive diagnostic evaluation, including genetic testing, metabolic studies, and imaging studies (such as MRI), may be necessary to confirm the diagnosis of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency [4].

References:

[1] Context 2 [2] Context 2 [3] Context 5 [4] Context 7