beta-mannosidosis

Beta-Mannosidosis: A Rare Inherited Disorder

Beta-mannosidosis, also known as lysosomal beta-mannosidase deficiency, is a rare inherited disorder that affects the way certain sugar molecules are processed in the body [1]. This condition is caused by a decrease in the activity of the enzyme beta-mannosidase, which is coded for by the gene MANBA located at 4q22-25 [5].

Inheritance and Genetics

Beta-mannosidosis is inherited in an autosomal recessive manner, meaning that affected individuals are born with two copies of the mutated gene, one from each parent [1]. This condition can affect individuals of any age, from infancy to adulthood, and the severity of symptoms can vary widely [4].

Symptoms and Presentation

The presentation of beta-mannosidosis can be highly variable, ranging from mild symptoms that may not become apparent until later in childhood or adolescence to a rapidly progressive illness with early onset symptoms [6]. Some individuals may experience an accumulation of sugar molecules in the body, leading to various health problems [2].

Diagnosis and Frequency

Beta-mannosidosis is often misdiagnosed or undiagnosed due to its rarity and variable presentation [3]. As of May 2023, it is estimated that approximately 20 individuals worldwide have been reported with this condition [3]. Accurate diagnosis requires genetic testing and analysis.

References:

[1] Context result 1 [2] Context result 6 [3] Context result 3 [4] Context result 4 [5] Context result 1 [6] Context result 6

Signs and Symptoms of Beta-Mannosidosis

Beta-mannosidosis is a rare inherited disorder that affects the way certain sugar molecules are processed in the body. The signs and symptoms of this condition can vary widely in severity and age of onset, ranging from infancy to adulthood.

• Intellectual Disability: Almost all individuals with beta-mannosidosis experience some degree of intellectual disability [1][2].
• Delayed Motor Development: Some affected individuals may have delayed motor development, which can manifest as difficulty walking or standing [3][7].
• Seizures: Seizures are a common symptom of beta-mannosidosis, and can range from mild to severe [4][9].
• Speech and Hearing Difficulties: Affected individuals may experience speech and hearing difficulties, which can be mild or severe [6][8].
• Muscle Abnormalities: Muscle abnormalities, such as muscle weakness or wasting, can also occur in some cases [1][5].
• Reduced Sensations: Some individuals with beta-mannosidosis may experience reduced sensations in their extremities [1].

It's worth noting that the age of onset and severity of symptoms can vary widely among affected individuals. In some cases, symptoms may not appear until adulthood.

References:

[1] Context result 1 [2] Context result 2 [3] Context result 7 [4] Context result 9 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 11 [9] Context result 9

Beta-mannosidosis is a rare lysosomal storage disease, and its diagnosis can be challenging due to its rarity and variability in clinical presentation. However, several diagnostic tests are available to confirm the diagnosis.

• Blood test: A blood test to measure beta-mannosidase enzyme activity in blood plasma or white blood cells (leukocytes) is a useful first-tier test for patients with a clinical suspicion of beta-mannosidosis [1]. This biochemical test can reveal less activity than expected, which is considered the gold standard to confirm a diagnosis of beta-mannosidosis [2].
• Molecular analysis: Molecular analysis of the gene for Beta-mannosidosis (MANBA) is also available for identification of the causative mutation within a family, carrier status, and prenatal diagnosis [3]. This test can be used to confirm a suspected Beta-mannosidosis syndrome diagnosis.
• Urine test: Urine testing to identify abnormal oligosaccharides is a useful screening test, and enzymatic analysis or molecular testing can be used for confirmation [12].
• Sequence analysis: Sequence analysis of the entire coding region of the MANBA gene is also available for diagnostic purposes [7].

These tests are typically performed by specialized laboratories that have experience in diagnosing lysosomal storage diseases. It's essential to consult with a geneticist or a specialist in pediatric neurology for accurate diagnosis and management.

References:

[1] Context 1 [2] Context 2 [3] Context 4

Differential Diagnosis of Beta-Mannosidosis

Beta-mannosidosis, a rare lysosomal storage disease, can be challenging to diagnose due to its variable clinical presentation and overlapping symptoms with other conditions. The differential diagnosis for beta-mannosidosis includes:

• Mucopolysaccharidosis (MPS): A group of genetic disorders caused by the deficiency of enzymes involved in the breakdown of mucopolysaccharides, leading to accumulation of these substances in various tissues.
• Gangliosidosis: A lysosomal storage disease characterized by the accumulation of gangliosides, a type of lipid molecule, in neurons and other cells.
• Mucolipidosis type II: A rare genetic disorder caused by the deficiency of the enzyme alpha-N-acetylglucosaminidase, leading to the accumulation of mucopolysaccharides and glycoproteins in various tissues.
• Sialidosis type II: A lysosomal storage disease characterized by the deficiency of the enzyme sialidase, leading to the accumulation of sialic acid-containing molecules in various tissues.
• Fucosidosis: A rare genetic disorder caused by the deficiency of the enzyme alpha-L-fucosidase, leading to the accumulation of fucose-containing molecules in various tissues.

These conditions can present with similar symptoms to beta-mannosidosis, such as developmental delay, mental retardation, and seizures. Therefore, a comprehensive diagnostic evaluation is essential to distinguish between these conditions and accurately diagnose beta-mannosidosis.

References:

• [2] - In summary, β-mannosidosis must thus now be considered in the differential diagnosis of neonatal onset seizures, and the potential for the development of ...
• [5] - Beta-mannosidosis is inherited in an autosomal recessive manner. Affected individuals may present with a range of symptoms, including developmental delay, mental retardation, and seizures.
• [7] - A detailed patient and family history, a thorough clinical evaluation, and a variety of specialized tests are essential for diagnosing beta-mannosidosis.
• [10] - A blood test to measure beta-mannosidase enzyme activity in blood plasma or white blood cells (leukocytes) can reveal less activity than expected, supporting the diagnosis of beta-mannosidosis.