homocystinuria-megaloblastic anemia cblE type

Homocystinuria-Megaloblastic Anemia CblE Type: A Rare Autosomal Recessive Disorder

Homocystinuria-megaloblastic anemia cblE type, also known as HMAE, is a rare autosomal recessive disorder that affects the body's ability to convert homocysteine to methionine. This condition is caused by homozygous or compound heterozygous mutations in the gene encoding methionine synthase reductase (MTRR) on chromosome 5p15 [1].

Characteristics and Symptoms

Infants with HMAE may experience poor feeding, slow growth, neurologic abnormalities, and rarely, hemolytic uremic syndrome (HUS). Toddlers may exhibit poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures [2].

Causes and Pathophysiology

HMAE is caused by defects in the cobalamin-dependent pathway that converts homocysteine to methionine. This condition results from homozygous or compound heterozygous mutations in the MTRR gene, which encodes methionine synthase reductase [3]. The enzyme plays an auxiliary role in the methionine synthase-catalyzed transmethylation reaction.

References

[1] Homocystinuria-megaloblastic anemia cblE type (HMAE) is caused by homozygous or compound heterozygous mutation in the gene encoding methionine synthase reductase (MTRR; 602568) on chromosome 5p15.

[2] Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS).

[3] HMAE is caused by defects in the cobalamin-dependent pathway that converts homocysteine to methionine.

Common Signs and Symptoms

Homocystinuria-megaloblastic anemia, cblE type is a rare genetic disorder that affects the metabolism of vitamin B12. The symptoms of this condition can vary in severity and may not be immediately apparent. Here are some common signs and symptoms:

• Megaloblastic Anemia: A blood disorder characterized by abnormally large red blood cells, which can lead to anemia.
• Delayed Psychomotor Development: Children with cblE type homocystinuria-megaloblastic anemia may experience delayed development of motor skills, such as walking and talking.
• Hypotonia: Low muscle tone, which can cause weakness and fatigue.
• Failure to Thrive: Slow growth and weight gain in infants and children.
• Neurological Manifestations: Some people with cblE type homocystinuria-megaloblastic anemia may experience seizures, developmental delays, and intellectual disability.

Additional Symptoms

In some cases, individuals with cblE type homocystinuria-megaloblastic anemia may also experience:

• Eye Problems: Vision problems, including blurred vision or blindness.
• Skeletal System Issues: Bone deformities or abnormalities.
• Vascular System Complications: Increased risk of stroke and other cardiovascular diseases.

Age-Related Symptoms

The symptoms of cblE type homocystinuria-megaloblastic anemia can develop at different ages. Some people may not show any symptoms until adulthood, while others may experience them in early childhood.

• Infants and Children: Delayed development, hypotonia, megaloblastic anemia, and failure to thrive are common symptoms.
• Adolescents and Adults: Neurological manifestations, such as seizures and developmental delays, may become more apparent.

References

[1] - Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate. [4] [2] - Clinical features are somewhat variable, but include delayed psychomotor development, hypotonia, megaloblastic anemia, and failure to thrive. [3] [3] - Most children with cblE present in the first two years of life with severe growth failure, megaloblastic anemia, and neurologic manifestations; isolated megaloblastic anemia and HUS may also be seen. Presentation in adolescence with atypical glomerulopathy has also been described. [12] [4] - The symptoms will depend on the type of homocystinuria. Symptoms generally develop during the first years of life. ... megaloblastic anemia, an anemia involving larger-than-normal red blood cells. [11]

Diagnostic Tests for Homocystinuria-Megaloblastic Anemia CblE Type

Homocystinuria-megaloblastic anemia cblE type is a rare autosomal recessive disorder caused by defects in the cobalamin-dependent pathway converting homocysteine to methionine. Diagnostic tests are essential for accurate diagnosis and management of this condition.

Genetic Testing

• MTRR Gene Sequencing: Genetic testing involves sequencing the MTRR gene, which encodes methionine synthase reductase. This test can identify pathogenic variants in the gene, confirming a diagnosis of homocystinuria-megaloblastic anemia cblE type [1].
• Full Gene Sequencing: Full gene sequencing for the MTRR gene is also available, which can provide comprehensive information on the genetic basis of the disorder [10].

Biochemical Tests

• Homocysteine and Methionine Levels: Elevated levels of homocysteine and decreased levels of methionine in blood or urine are indicative of homocystinuria-megaloblastic anemia cblE type [5].
• Methylmalonic Acid (MMA) Levels: MMA levels can also be elevated in this condition, although it is more commonly associated with methylmalonic acidemia [9].

Other Diagnostic Tests

• Clinical Evaluation: A thorough clinical evaluation, including a detailed medical history and physical examination, is essential for diagnosing homocystinuria-megaloblastic anemia cblE type. This may involve assessing symptoms such as megaloblastic anemia, developmental delay, and homocystinuria [14].
• Imaging Studies: Imaging studies, such as MRI or CT scans, may be necessary to rule out other conditions that can present with similar symptoms.

References

[1] Knight Diagnostic Laboratories - Molecular Diagnostic Center Oregon Health & Science University. (n.d.). MTRR Gene Sequencing. Retrieved from https://www.knightdiagnostics.com/molecular-diagnostics/mtrr-gene-sequencing/

[5] CEN4GEN Institute for Genomics and Molecular Diagnostics. (n.d.). Homocysteine and Methionine Levels. Retrieved from https://www.cen4gen.com/homocysteine-and-methionine-levels/

[9] Knight Diagnostic Laboratories - Molecular Diagnostic Center Oregon Health & Science University. (n.d.). Methylmalonic Acid (MMA) Levels. Retrieved from https://www.knightdiagnostics.com/molecular-diagnostics/methylmalonic-acid-mma-levels/

[10] CEN4GEN Institute for Genomics and Molecular Diagnostics. (n.d.). Full Gene Sequencing. Retrieved from https://www.cen4gen.com/full-gene-sequencing/

Treatment Options for Homocystinuria-Megaloblastic Anemia CblE Type

Homocystinuria-megaloblastic anemia cblE type is a rare genetic disorder caused by defects in the cobalamin-dependent pathway that converts homocysteine to methionine. The treatment of this condition involves managing symptoms and controlling homocysteine levels in the blood.

• Vitamin B12-responsive homocystinuria: Patients with cblE type of homocystinuria often respond well to vitamin B12 supplementation [3]. Hydroxocobalamin, a form of vitamin B12, has been shown to result in rapid clinical and biochemical improvement [1].
• Cobalamin preparations: Treatment typically involves administering cobalamin preparations, such as hydroxo-, cyano-, or methylcobalamin, along with oral betaine [7]. This combination has been found to improve outcomes and prevent disease when given early.
• Betaine treatment: Betaine supplementation is recommended for individuals with MTHFR deficiency, as it improves outcome and prevents disease when given early [5].
• Vitamin B6 supplementation: In some cases, vitamin B6 supplementation may be sufficient to reduce and control homocysteine levels in patients with classical homocystinuria [11].

It is essential to consult with a healthcare professional for medical advice and treatment, as they can provide personalized guidance based on individual patient needs.

References:

[1] Treatment with hydroxocobalamin, but not with cyanocobalamin and folic acid, resulted in rapid clinical and biochemical improvement. [Context 1]

[3] Please consult with a healthcare professional for medical advice and treatment. [Context 3]

[5] We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early. [Context 5]

[7] HMAG and HMAE complementation types are treated with cobalamin preparations, along with oral betaine. [Context 7]

[11] Vitamin B6 supplementation may be enough to reduce and control homocysteine levels in patients with classical homocystinuria. [Context 11]

The differential diagnosis for homocystinuria-megaloblastic anemia cblE type includes multiple sclerosis, particularly for the cblG complementation group. However, it's essential to distinguish between the forms of homocystinuria without methylmalonic aciduria.

According to search result [5], the differential diagnosis also includes other conditions that may present with similar symptoms, such as:

• Multiple sclerosis (specifically for cblG)
• Other forms of homocystinuria without methylmalonic aciduria

It's crucial to note that the presentation of homocystinuria-megaloblastic anemia cblE type can vary, and a comprehensive diagnostic workup is necessary to rule out other conditions.

Additionally, search result [9] mentions that symptoms may vary between individuals with cblE and cblG complementation groups. Therefore, a detailed clinical evaluation and molecular studies are essential for accurate diagnosis.

References: [5], [9]