About mucopolysaccharidosis iv
What is mucopolysaccharidosis iv?
Morquio syndrome (mucopolysaccharidosis type IV; MPS IV) is a mucopolysaccharide storage disease that exists in two forms (Morquio syndromes A and B) and occurs because of a deficiency of the enzymes N-acetyl-galactosamine-6-sulfatase and beta-galactosidase, respectively. A deficiency of either enzyme leads to the accumulation of mucopolysaccharides in the body, abnormal skeletal development, and additional symptoms. In most cases, individuals with Morquio syndrome have normal intelligence. The clinical features of MPS IV-B are usually fewer and milder than those associated with MPS IV-A. Symptoms may include growth retardation, a prominent lower face, an abnormally short neck, knees that are abnormally close together (knock knees or genu valgum), flat feet, abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis), abnormal development of the growing ends of the long bones (epiphyses), and/or a prominent breast bone (pectus carinatum). Hearing loss, weakness of the legs, and/or additional abnormalities may also occur.
The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain carbohydrates and fats. In individuals with MPS disorders, deficiency or malfunction of specific lysosomal enzymes leads to an abnormal accumulation of certain complex carbohydrates (mucopolysaccharides or glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth. These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow. This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body. There are several different types and subtypes of mucopolysaccharidosis. These disorders, with one exception, are inherited as autosomal recessive traits.
What are the symptoms for mucopolysaccharidosis iv?
Abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis) or concern for a spine abnormality symptom was found in the mucopolysaccharidosis iv condition
Mucopolysaccharidosis IV (MPS IV) is a rare, progressive health condition caused by gene abnormalities. Although a metabolic disorder, it mainly affects the patient’s skeletal structure, resulting in stalled growth and bone malformations. The disease is also called Morquio Syndrome.
Mucopolysaccharidosis IV manifests as two types- Type A and Type B, based on the type of gene mutation that underlies the condition. These types cannot be differentiated based on the symptoms displayed. The disease indicators and their severity vary from person to person.
Signs and Symptoms
In MPS IV patients, the onset of illness starts early in childhood, between one and three years. By 18 months, the physical growth starts to slow down, and it completely stops around eight years of age. The main symptoms include:
1. Skeletal Abnormalities- Shortened long bones resulting in the short physical build-up, bell-shaped chest, knock knees, spine curvature, dysplasia or abnormal cell growth of hips, wrists, or waist, and hypermobility or restricted movement of joints.
2. Underdeveloped Odontoid Process (Odontoid Hypoplasia)¬- Odontoid process is a peg-like bone in the neck, which aids in the lateral rotation of cervical vertebrae. A major sign of Mucopolysaccharidosis IV is a malformed odontoid process resulting in a condition called odontoid hypoplasia, which could lead to misalignment of the cervical spine resulting in damage to the spinal cord.
3. Vision And Auditory Issues- Cloudy cornea resulting in loss of vision, frequent ear infections, and loss of hearing are common symptoms.
4. Heart, Pulmonary, and Hepatic Issues¬- MPS IV patients may suffer from heart valve abnormalities or moderately enlarged liver. In some people, the lungs could become congested, causing frequent upper respiratory tract infections (URTI) and sleep apnea.
5. Symptoms Related to Physical Appearance- Persons with MPS IV will have slightly coarse facial features like a protruded forehead or a prominent lower face. Patients suffer from weakened tooth enamel and multiple cavities. Other physical deformities include a softly protruding belly button (umbilical hernia) or bulged lower abdomen.
Symptoms
Growth delays,A prominent lower face,Abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis) or concern for a spine abnormality,An abnormally short neck,Knees that are abnormally close together (knock knees or genu valgum),Flat feet,Abnormal development of the growing ends of the long bones (epiphyses),Hip dislocation and arthritis and/or a prominent breast bone (pectus carinatum),Hearing loss, Weakness of the legs, and/or additional abnormalities may also occur
Conditions
Group of inherited lysosomal storage disorders
Drugs
Enzyme replacement therapy (elosulfase alfa, or Vimizim),Surgery
What are the causes for mucopolysaccharidosis iv?
Mucopolysaccharidosis IV (MPS IV) or Morquio Syndrome is an inherited health condition caused by mutated genes. It belongs to a group of rare metabolic disorders called Mucopolysaccharidosis (MPS). MPS diseases are caused by the malfunction of lysosomes in human cells. Lysosomes are those constituents of cells that produce the enzymes needed to break down proteins, carbohydrates, lipid molecules, nucleic acids, etc. When lysosomes fail to produce sufficient enzymes or don’t produce the enzymes at all, it results in progressive cell damage, causing severe health conditions such as Mucopolysaccharidosis IV.
Etiology of MPS IV
1. MPS IV originates because of missing or deficient enzymes N-acetylgalactosamine-6-sulfatase and beta-galactosidase. These two enzymes are needed to break the keratan sulfate sugar chains.
2. The genes that give instructions on the production of these chemicals are known as GALNS and GLB1 genes.
3. Any mutation in these genes interferes with enzyme production in the cell. As a result, keratan sulfate sugar molecules fail to get broken down, accumulate in the cells, and gradually lead to permanent cell damage.
4. If the build-up of unbroken sugar molecules in the cells reaches lethal levels, it will cause further damage to organs and bones. Such accumulations may also affect the absorption of other proteins inside lysosomes resulting in additional health complications.
5. Mucopolysaccharidosis IV caused by GALNS manifests as MPS IV Type A. If caused by GLB1, then the condition is called MPS IV Type B. Clinical indicators are similar in both types, but symptoms appear milder in Type B MPS IV.
How is MPS IV Inherited?
1. MPS IV is an autosomal recessive disorder, meaning the patient inherits both copies of defective genes from the parents.
2. Normally, only one copy of the gene is required for processing keratan sulfate molecules.
3. But when both copies passed down are pathogenic variants, the person lacks functioning genes causing Mucopolysaccharidosis IV.
Symptoms
Growth delays,A prominent lower face,Abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis) or concern for a spine abnormality,An abnormally short neck,Knees that are abnormally close together (knock knees or genu valgum),Flat feet,Abnormal development of the growing ends of the long bones (epiphyses),Hip dislocation and arthritis and/or a prominent breast bone (pectus carinatum),Hearing loss, weakness of the legs, and/or additional abnormalities may also occur
Conditions
Group of inherited lysosomal storage disorders
Drugs
Enzyme replacement therapy (elosulfase alfa, or Vimizim),Surgery
What are the treatments for mucopolysaccharidosis iv?
Mucopolysaccharidosis IV, known as MPS iv and Morquio syndrome, is one of the rarest genetic disorders. In this disease, the body lacks the required level of enzymes to break down glycosaminoglycans (a chain of sugar molecules) into proteins. Therefore, these molecules tend to build up and create various health-related issues in the human body. It is of two types MPS IVA and MPS IVB.
The various treatments and therapies of mucopolysaccharidosis IV are symptoms based. These symptoms differ from person to person but are also similar in many cases. Henceforth, a team of orthopedic surgeons, physiotherapists, neurosurgeons, and other such specialists recommends some physical examinations of the patient (including some X-rays, medical history, urine tests, etc.) before deciding the type of treatment to be applied to the concerned patient.
Some of the treatments are-
1. HSCT- Hematopoietic stem cell transplantation is used to correct enzyme deficiency in patients diagnosed with mucopolysaccharidosis IV. In this treatment, stem cells from the healthy donor's body are transplanted into the diseased individual. After which, these cells multiply and produce all the essential enzymes, including the one that was deficient in the patient.
2. EST- Enzyme replacement therapy is long-lasting therapy and takes about one to four hours for the infusions. In this treatment, the regular infusion of recombinants is done to overcome the deficiency of the enzyme in the patient with mucopolysaccharidosis IV.
Symptoms
Growth delays,A prominent lower face,Abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis) or concern for a spine abnormality,An abnormally short neck,Knees that are abnormally close together (knock knees or genu valgum),Flat feet,Abnormal development of the growing ends of the long bones (epiphyses),Hip dislocation and arthritis and/or a prominent breast bone (pectus carinatum),Hearing loss, weakness of the legs, and/or additional abnormalities may also occur
Conditions
Group of inherited lysosomal storage disorders
Drugs
Enzyme replacement therapy (elosulfase alfa, or Vimizim),Surgery
What are the risk factors for mucopolysaccharidosis iv?
Mucopolysaccharidosis IV, known as MPS iv and Morquio syndrome, is one of the rarest genetic disorders. In this disease, the body lacks the required level of enzymes to break down glycosaminoglycans (chain of sugar molecules) into proteins. Therefore, these molecules tend to build up and create various health-related issues in the human body.
The risk factors in mucopolysaccharidosis iv are mostly because of a genetic disorder. This depends on family medical history. However, the following are the determining risk factors-
1. Age- Equal chance for males and females. From birth to any age. Most common in infants and children of age group 2-11 years.
2. Genetic disorder- It is inherited from the genes of a person having any such medical history and can be inherited from one generation to another.
3. Common effects- The effects include knocking knees, hip pain, spine abnormalities, and stiffness in joints, restricting one’s body movement.
4. Life expectancy- It depends on the symptoms of the individual. Those suffering from severe symptoms may live only up to late adolescence. Those with milder ones live till adulthood but with decreased life expectancy.
Above are some common risk factors involved in mucopolysaccharidosis iv. Therefore, one must consider these factors and schedule an appointment with the doctor when you feel discomfort in the areas mentioned above.
Symptoms
Growth delays,A prominent lower face,Abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis) or concern for a spine abnormality,An abnormally short neck,Knees that are abnormally close together (knock knees or genu valgum),Flat feet,Abnormal development of the growing ends of the long bones (epiphyses),Hip dislocation and arthritis and/or a prominent breast bone (pectus carinatum),Hearing loss, weakness of the legs, and/or additional abnormalities may also occur
Conditions
Group of inherited lysosomal storage disorders
Drugs
Enzyme replacement therapy (elosulfase alfa, or Vimizim),Surgery