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Mucopolysaccharides

 Mucopolysaccharides



Mucopolysaccharidoses (MPS) are a group of genetic disorders where the body can't properly break down certain complex sugar molecules called glycosaminoglycans (also known as mucopolysaccharides). These molecules are important components of bones, cartilage, skin, and other connective tissues. Due to enzyme deficiencies, these molecules accumulate in cells, leading to a range of physical and developmental problems

Symptoms

Skeletal abnormalities: Short stature, joint stiffness, spinal problems, and bone deformities (dysostosis multiplex) are common. 

Facial features: Distinctive facial features, such as a large head, prominent forehead, thick hair and eyebrows, and coarse facial features, are often observed. 

Organomegaly: Enlarged liver (hepatomegaly) and spleen (splenomegaly) are frequently seen. 

Vision and hearing problems: Cloudy corneas, glaucoma, and hearing loss can occur. 

Neurological issues: Some types of MPS, particularly MPS III, can cause developmental delays, intellectual disability, and neurological regression. 

Heart problems: Heart valve problems, cardiomyopathy, and arrhythmias can be present. 

Other: Hernias, sleep apnea, and frequent respiratory and ear infections can also occur, according to the National Institute of Neurological Disorders and Stroke. 

Specific symptoms can vary based on the type of MPS:

MPS I (Hurler syndrome):

Severe form with progressive intellectual disability, coarse facial features, and skeletal abnormalities. 

MPS II (Hunter syndrome):

Similar to MPS I but milder in some cases, with less severe intellectual disability. 

MPS III (Sanfilippo syndrome):

Primarily affects the brain and nervous system, leading to developmental regression, hyperactivity, and behavioral problems. 

MPS IV (Morquio syndrome):

Characterized by skeletal abnormalities and short stature, but with less severe intellectual disability. 

MPS VI (Maroteaux-Lamy syndrome):

Similar to MPS I, with coarse facial features and skeletal problems. 

Causes

Enzyme Deficiency:

MPS disorders arise from mutations in genes that provide instructions for producing specific enzymes. These enzymes are essential for breaking down GAGs within lysosomes, which are cellular compartments responsible for waste processing. 

GAG Accumulation:

When the necessary enzyme is missing or defective, GAGs cannot be properly broken down and accumulate within lysosomes. This buildup disrupts normal cellular function and can cause damage to various tissues and organs. 

Inheritance:

MPS disorders are typically inherited in an autosomal recessive manner, meaning that an individual needs to inherit two copies of the mutated gene (one from each parent) to develop the condition. In some cases, such as MPS II (Hunter syndrome), the inheritance pattern is X-linked recessive, affecting males more frequently. 

Specific Enzymes and Types of MPS:

There are at least 11 types of MPS, each caused by a deficiency in a different enzyme. For example: 

MPS I (Hurler syndrome): Caused by a deficiency in the enzyme alpha-L-iduronidase. 

MPS II (Hunter syndrome): Caused by a deficiency in the enzyme iduronate sulfatase. 

MPS VII (Sly syndrome): Caused by a deficiency in the enzyme β-glucuronidase. 

Consequences of GAG Accumulation:

The accumulation of GAGs can lead to a wide range of symptoms, including: 

Skeletal abnormalities: Short stature, joint stiffness, and bone deformities. 

Organomegaly: Enlargement of organs like the liver and spleen. 

Cardiovascular problems: Heart valve defects and other heart-related issues. 

Respiratory problems: Breathing difficulties due to airway obstruction or lung problems. 

Neurological issues: Developmental delays, intellectual disability, and other neurological complications. 

Other symptoms: Corneal clouding, hearing loss, and other symptoms depending on the specific type of MPS

Diagnosis

1. Clinical Evaluation:

Physical Examination:

Doctors look for characteristic physical features like short stature, skeletal abnormalities (dysostosis, kyphosis), coarse facial features, joint stiffness, and enlarged organs. 

Medical History:

A thorough review of the patient's medical history, including developmental milestones, is crucial. 

Imaging:

X-rays and other imaging techniques (like MRI) help assess skeletal and organ involvement. 

2. Biochemical Testing:

Urine GAG Analysis:

Elevated levels of specific glycosaminoglycans (GAGs) in urine are a strong indicator of MPS. Both quantitative (measuring overall GAG levels) and qualitative (identifying specific GAG types) analysis are performed. 

Enzyme Assays:

These tests measure the activity of specific lysosomal enzymes in cells (like fibroblasts or leukocytes) or blood. A deficiency or absence of the enzyme corresponding to the suspected MPS type confirms the diagnosis. 

3. Genetic Testing:

Molecular Genetic Testing:

Identifies mutations in the genes responsible for producing the deficient enzyme. This confirms the specific type of MPS and is crucial for genetic counseling.

Prenatal Testing:

Genetic testing can be performed on prenatal samples (chorionic villi or amniocytes) to diagnose MPS in fetuses. 

4. Additional Testing:

Echocardiography: Evaluates heart function and structure, as cardiovascular problems are common in MPS. 

Ophthalmological Evaluation: Assess for eye problems, as some MPS types can cause vision loss. 

Audiological Assessment: To check for hearing loss, which can be a feature of certain MPS types. 

Treatment

Enzyme Replacement Therapy (ERT):

This is a first-line treatment for some MPS types, where the missing enzyme is replaced through intravenous infusions. For example, laronidase (Aldurazyme) is used in MPS I. 

Hematopoietic Stem Cell Transplantation (HSCT):

This procedure involves replacing damaged cells with healthy cells from a donor, often used in severe cases of MPS I (Hurler syndrome). It can improve life expectancy and reduce disease progression. 

Symptomatic Treatment:

This involves addressing specific organ damage and complications. This can include surgery for skeletal abnormalities (like kyphosis), addressing heart problems, respiratory issues, and managing gastrointestinal issues, among others, according to Medscape. 

Other Potential Therapies:

Clinical trials are exploring other options like intrathecal ERT (directly into the spinal fluid) and gene therapy, says a review in PMC

Type of Doctor Department :   A medical geneticist and a pediatrician or internist familiar with metabolic disorders.

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