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Mucopolysaccharidosis - Causes, Inheritance, Types, Symptoms, Diagnosis, and Treatment

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Mucopolysaccharidosis is a class of metabolic disorders characterized by the absence or dysfunction of glycosaminoglycans.

Written by

Dr. Vennela. T

Medically reviewed by

Dr. Kaushal Bhavsar

Published At June 22, 2023
Reviewed AtJanuary 2, 2024

Introduction

Lysosomal storage disorders that are hereditary are known as mucopolysaccharidoses (MPS). An abnormal buildup of specific complex carbohydrates (mucopolysaccharides or glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth occurs in people with MPS diseases due to a deficit or dysfunction of particular lysosomal enzymes. Additionally, the liver, spleen, blood, bone marrow, central nervous system, and respiratory system may all contain these accumulations. Cells, tissues, and different human organ systems eventually suffer increasing damage as a result of this accumulation.

What Causes Mucopolysaccharidosis?

The absence or dysfunction of a particular lysosomal enzyme required for the breakdown of dermatan sulfate, heparan sulfate, or keratan sulfate, either separately or collectively, causes all MPS diseases. These mucopolysaccharides build up in cells, tissues, and organs all over the body when they are not broken down. Except for Hunter syndrome, which is an X-linked recessive trait, all of these illnesses are inherited as autosomal recessive traits.

How Is Mucopolysaccharidosis Inherited?

  • Autosomal Recessive Trait: The genes for each disorder's enzyme, one of which is inherited from the mother and one from the father, exhibit unusual modifications in genetic disorders. When a person receives a defective gene for the same characteristic from both parents, recessive genetic diseases develop. A person will be a carrier for the disease if they have one normal gene and one sick gene, although they often will not exhibit any symptoms. Each pregnancy has a probability of 25 percent of producing an offspring with the disorder if both parents are carriers for the defective gene. Each pregnancy has a 50 percent chance of resulting in a child who shares a gene with one of the parents. A child has a 25 percent probability of inheriting normal genes from both parents and being genetically normal for that specific trait.

  • X-Linked Recessive Trait: Genetic illnesses known as X-linked recessive genetic disorders are brought on by a faulty gene on the X chromosome. X chromosomes are present in females in two copies, but one of them is "turned off," meaning that none of its genes are active. A female who carries the disease on one of her X chromosomes is known as a carrier. Because the defective gene is often shut down on the X chromosome in carrier females, these individuals typically do not exhibit symptoms of the condition. Men only have one X chromosome; therefore, if they inherit one with a sickness gene, they will get the illness. Every daughter of a man with an X-linked condition will carry the sickness gene. Because males usually pass their Y chromosome rather than their X chromosome to male progeny, they are unable to pass an X-linked gene to their sons. With each pregnancy, female carriers of X-linked disorders have a 25 percent chance of having a daughter who is also a carrier, a 25 percent risk of having a daughter who is not a carrier, a 25 percent probability of having a son with a disease and a 25 percent chance of having a son without a medical condition.

What Are the Signs and Symptoms of Mucopolysaccharidosis?

Although the severity of the mucopolysaccharidoses varies, they nonetheless share a number of clinical characteristics. These characteristics may be present at birth, but they develop when the accumulation of glycosaminoglycans affects the bones, connective tissues, and organs. The onset or presentation age varies greatly. Additionally, the life expectancy of those with MPS is considerably reduced.

1. Neurological Symptoms:

  • Damage to neurons, which are specialized nerve cells that transmit and receive information throughout the body, may result in neurological disorders.

  • Pain and decreased motor function (the ability to initiate and control muscular activity) can result from compressed nerves or nerve roots in the spinal cord or in the peripheral nervous system.

  • The peripheral neural system links the brain and spinal cord to other bodily organs, muscles, and tissues, as well as sensory organs like the eyes.

  • Those who are affected may have severe intellectual difficulties, developmental delays, or serious behavioral issues.

Numerous people struggle with the following:

  • Hyperactivity.

  • Depression.

  • Speech.

  • Impairment of hearing.

Some mucopolysaccharidoses frequently result in hydrocephalus, an excessive buildup of cerebrospinal fluid in the brain that can lead to increased pressure inside the head.

2. Ocular Symptoms: The person's eyesight may be impacted by glaucoma, retinal degeneration, and intracellular storage, which frequently causes the cornea of the eye to become clouded.

3. Physical signs:

  • Coarse facial traits, such as a thick tongue and mouth and a flat nasal bridge.

  • Dwarfism refers to a small stature and an abnormally short trunk or torso.

  • Abnormalities in bone structure, such as dysplasia and other skeletal anomalies.

  • Extra-thick skin.

  • Enlarged organs like the liver or spleen.

  • Hernias.

  • Hand movement and function are restricted by carpal tunnel syndrome.

  • Obstructive airway disease, recurrent respiratory infections, and obstructive sleep apnea are all very prevalent.

  • Heart illness is frequently accompanied by oversized or unhealthy heart valves.

What Are the Types of Mucopolysaccharidosis?

There are various subtypes of mucopolysaccharidoses, including seven unique clinical categories. Despite the fact that each case of mucopolysaccharidosis (MPS) is unique clinically, the majority of patients go through a period of normal development followed by a loss in their physical and mental abilities.

  • MPS I: Hurler, Hurler-Scheie, and Scheie are the three traditional classifications of MPS I based on the severity of symptoms in decreasing order.

  • MPS II: Iduronate sulfatase, an enzyme that breaks down the glycosaminoglycans heparan sulfate and dermatan sulfate inside of cells, is absent in MPS II, also known as Hunter syndrome. MPS II is likewise regarded as a continuous spectrum of disease, despite the fact that it was originally split into two groups based on the severity of symptoms.

  • MPS III: Sanfilippo syndrome, another name for MPS III, is characterized by severe neurological symptoms such as increasing dementia, aggressive behavior, hyperactivity, seizures, some loss of hearing and vision, and an inability to sleep for more than a few hours at a time.

  • MPS IV: The enzymes N-acetylgalactosamine 6-sulfatase (Type A) or beta-galactosidase (Type B), which are required to break down the keratan sulfate sugar chain, are absent or defective in two forms of MPS IV, also known as Morquio syndrome. Despite MPS IVB's milder appearance, both kinds of MPS share clinical traits. The onset period lasts between one and three years of age. Hearing loss, clouded corneas, and spinal nerve and nerve root compression brought on by severe, progressive skeletal alterations are examples of neurological consequences. A normal level of intelligence exists until hydrocephalus develops and is not corrected.

  • MPS VI: N-acetylgalactosamine 4-sulfatase, commonly known as Maroteaux-Lamy syndrome, is a defective enzyme that contributes to MPS VI. A wide variety of severe symptoms are present in MPS VI. The intellectual development of children is often average, but they also exhibit many of the physical symptoms of severe MPS I. Individuals with MPS VI experience a thickening of the dura (the membrane that surrounds and protects the brain and spinal cord), many of the neurological issues observed in other MPS illnesses, and may lose their hearing. Eye issues include corneal clouding, glaucoma (a set of diseases that harm the optic nerve), optic nerve or disk swelling, and optic nerve degeneration.

  • MPS VII: The mucopolysaccharidosis MPS VII, sometimes referred to as Sly syndrome, is one of the less frequent types. The condition is brought on by a beta-glucuronidase enzyme deficiency. Children with MPS VII, which is a rare condition, are born with hydrops fetalis, a condition in which the body retains a great deal of fluid. In these situations, survival is typically limited to a few months. The majority of MPS VII patients have less severe symptoms. By the age of three, minor to moderate intellectual disability may be present. Other neurological symptoms include hydrocephalus, nerve entrapment, partial vision loss, joint stiffness, and restricted movement. Some people may experience recurring episodes of pneumonia throughout their first few years of life in addition to skeletal issues. The majority of MPS VII patients reach their teens or later.

  • MPS IX: Dysfunction of the enzyme hyaluronidase causes MPS IX disease. It is incredibly uncommon. Intelligence and joint movement are unaffected. Nodular soft tissue masses surrounding joints are a sign of the condition, as are episodes of excruciating swelling of the tissue masses and pain that disappears on its own after three days. Mild facial alterations, small stature, numerous soft tissue lumps, and minor bone degradation seen on pelvic radiography are further characteristics.

How Is Mucopolysaccharidosis Diagnosed?

  • The initial steps in diagnosing MPS include a clinical examination and tests to look for excessive mucopolysaccharide excretion in the urine.

  • To make a certain diagnosis, enzyme assays that check different types of cells or blood in culture for an enzyme deficiency are required.

  • Amniocentesis and chorionic villus sampling used in prenatal diagnostics can determine whether a fetus is affected by the condition.

  • Parents who have a family history of MPS may benefit from genetic counseling to find out if they are carriers of the faulty gene that causes the disease.

How Is Mucopolysaccharidosis Treated?

For these conditions, there is currently no treatment. Treatment of systemic illnesses and enhancing a person's quality of life are the goals of medical treatment. Dietary modifications will not stop an illness from getting worse.

  • Surgery: Surgery can assist the release of nerves and nerve roots that have been squeezed by skeletal and other deformities as well as remove extra cerebrospinal fluid from the brain. Patients with severe corneal clouding may benefit from corneal transplants in terms of vision improvement. Tonsils and adenoids can be removed to help people with sleep apnea and obstructive airway problems breathe better. In order to help some people breathe, an endotracheal tube may need to be surgically implanted.

  • Enzyme Replacement Treatment: For MPS I, MPS II, MPS IVA, MPS VI, and MPS VII, enzyme replacement treatment is currently in use, and it is also being studied for other MPS illnesses. Although it does not treat the disease's neurological symptoms, it has shown promise in easing pain and other non-neurological symptoms.

  • Bone Marrow Transplantation (BMT) And Umbilical Cord Blood Transplantation (UCBT): The treatment of mucopolysaccharidoses with bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) has been largely unsuccessful. Except for those that impair the skeleton and eyes, abnormal physical traits may be improved, but neurologic results have been inconsistent. Since BMT and UCBT are high-risk procedures, they are often only carried out after family members have undergone thorough assessment and counseling.

  • Physical Therapy: Daily exercise and physical therapy may prevent joint issues and enhance mobility.

Conclusion

Despite being uncommon hereditary LSD diseases, MPS pose a serious medical and societal issue due to their high mortality and high cost of care. MPS patients need extensive treatment, and doctors need to be very aware of them because of their severe and developing symptoms. Early identification of MPS will be made easier by understanding the signs and symptoms that differ between subtypes as well as their onset. The symptoms of many subtypes, however, frequently resemble one another and are difficult to distinguish. Treatment for both the severe and moderate forms of MPS is prioritized more. Misdiagnosis is frequently caused by common clinical characteristics, including low stature and mental impairment. In order to protect organic functioning and enhance the quality of life, early diagnosis is crucial.

Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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