Mucopolysaccharidosis – causes, symptoms, diagnosis, treatment

The inherited situation in which the body is not able to break down or change the sugar molecule to simple form is known as mucopolysaccharidosis.

Introduction:

These sugar molecules are also present in the body. These sugars also build up with the growth of cells and tissues and cause health problems. About seven subtypes of this disease also identified the people suffering from this disease look normal and healthy at the time of birth.

 But after development, they face mental and physical diseases. As conditions develop some physical and abnormalities are cognitive development. Some are in an autosomal recessive manner. The genetic disorder follows the X connected example of legacy. The treatment is begun by the side effects of every patient.

What are other diseases caused by mucopolysaccharidosis

  • Inguinal hernia
  • Air infections
  • Carpal tunnel syndrome
  • Spinal stenosis
  • Carnell clouding
  • Joint problem
  • Heart disease or heart failure
  • Problems with bones, especially ribs
  • Developmental delay

What are types of Mucopolysaccharidosis

Type-I Mucopolysaccharidosis

 Type I Mucopolysaccharidosis which is also called as MPS-I is a disorder that causes problems in the several body organs and is categorized into 3 types of diseases: these diseases are

  • Muco-PS-I H named as Hurler syndrome
  • Muco- PS-I H-S named as Hurler-Sekcie Syndrome
  • Muco-PS-I S named as Sechcie Syndrome

Causes of Muco-PS-I

 Much-PS-I is believed to be the result of the deformation occurring in the gene called IDUA; which lacks IDUA enzyme due to which Glycosaminoglycans (GAGs), which are large sugar molecules, accumulate in lysosome organelle. It results in an increase in the size of many organs and tissues of the body.

Symptoms of Muco-PS-I

 The prominent symptoms of Muco-PS-I disorder occur most likely during the early ages of childhood. These symptoms include:

  • Enlarged cheeks, lips, nose, and head.
  • Enlarged vocal cord; which results in a deep voice tone.
  • Infection of the respiratory tract.
  • Out-pouching around the belly button which is commonly known as umbilical hernia.
  • Abdominal disturbance.
  • Defects in ears and hearing abilities.
  • Joints become deformed.
  • Narrowing of the spinal cord.
  • Short height.

Diagnosis of Muco-PS-I

It is a genetic but a rare disease, its diagnosis is a big challenge. Physical examination of patients along with results of laboratory tests could make the diagnosis of the disorder.

Treatment of Muco-PS-I

The Muco-PS-I disorder can be treated in two ways

Hematopoietic stem cells transplants (HSCT)

HSCT is the best treatment for patients aged less than 2 years. It is effective for early disease processes.

Enzyme replacement therapy (ERT)

ERT is done with the drugs Laronidase or Aldurazyme. These drugs are effective for the problems regarding breath, heart, bones, joints, and growth. But this treatment cannot cure the mental issues, as these drugs cannot cross the blood-brain barrier.

Type-II Muco-PS

Type-II-Muco-PS also named as Muco-PS-II is the disorder mainly occurring in males and it is the disorder of the metabolism of carbohydrates.

It is classified on the basis of severity of disease as:

  • Mild Muco-PS-II (Attenuated)
  • Severe Muco-PS-II

This disorder has frequent progression. The people suffering from severe types of MPS-II can hardly live 10-20 years of age.

Causes of Muco-PS-II

Muco-PS-II is caused by the mutations occurring in the IDS gene. This disorder has X-linked inheritance.

Sign and symptoms

The sign and symptoms of Muco-PS-II include the following:

  • Enlarged spleen.
  • Enlarged liver.
  • Hearing loss.
  • Heart deformities.
  • Joint diseases.
  • Blockage of heart valves.
  • Behavioral abnormalities.
  • Depressed and flat nose.
  • Long and narrow head.

Diagnosis of Muco-PS-II

Testing of the Muco-PS-II can be done by testing the relative of an infected patient to determine the causes of this disorder/mutation.

 In case if no relative is available for testing, then sequence analysis is done which requires a blood sample & process of the IDS gene for looking at the errors. In case if the sequence analysis fails to look for mutation, then genetic tests are used to detect mutations that cause Muco-PS-II.

 Treatment of Muco-PS-II

 For the treatment of Muco-PS-II disorder, Iodo Sulphate is manufactured by FDA approval. This drug has been shown to improve the health of patients with hunters’ syndrome, MPS-II by enhancing their walking capacity.

Type III Mucopolysaccharidosis

Type III-Mucopolysaccharidosis also named as Sanfilippo syndrome, a genetic disorder in which a body becomes unable to hydrolyze complex sugars Lillie Glycosaminoglycans (GAGs). These sugars are called mucopolysaccharides.

More commonly people with this disorder cannot break down GAGs such as heparin sulfate. MPS III is categorized as A, B, C, and D. All these types have the same symptoms.

  • Muco-PS-type­­­­­­­­­­­­­­­­­­­­­­-3A (most severe)
  • Muco-PS-type-3B
  • Muco-PS-type-3C and
  • Muco-PS-type-3D.

Symptoms of Muco-PS III

The following symptoms can be seen in people with Muco-PS III:

  • Dementia
  • Aggressive behavior
  • Seizure
  • Deafness
  • Vision loss
  • Sleeping disturbance
  • Coarse hair texture
  • Excessive hairs on the body
  • Mental retardation
  • Chronic infection of the middle ear.

 Diagnosis of Muco-PS III

 It is a genetic but a rare disease, its diagnosis is a big challenge. Physical examination of patients along with results of laboratory tests could make the diagnosis of the disorder.

 Treatment of Muco-PS III

 There is no specific treatment of this disorder. Mostly the patients suffering from MPS III live a few years of their life and eventually die.

Type IV- Mucopolysaccharidosis

Type-4-Mucopolysaccharidosis is also named as Moquino syndrome, which is a metabolic disorder in which the patient’s body loses the ability to break down the sugar molecules present in long chains, especially mucopolysaccharides. That is why the high level of sugar lies within the cells causing various diseases.

 It has two forms

  • Muco-PS IV-A (due to the mutations in a gene named as GALNS)
  • Muco-PS IV-B (due to the mutations in a gene named as GLB1)

 Causes of Muco-PS-IV

The muco-PS-IV disorder is mainly caused by the mutations in two basic genes named as GALNS and GLB1 gene. Both genes encode for enzyme production which helps in the hydrolysis of complex sugars.

Signs and prominence of Muco-PS-IV

  • Abnormal heart functioning
  • Abnormal skin
  • Abnormal respiratory tract
  • Hypermobility of joints
  • Vision-loss or reduction
  • Sleep apnea
  • Lung’s diseases

Diagnosis of Muco-PS-IV

The diagnosis of this disorder includes the following techniques:

  • X-rays
  • Urine & blood tests
  • Eye examination
  • Skin fibroblast culture
  • Genetic testing to indicate GALNS or GLB1 gene.

Treatment

Treatment of the Muco-PS-IV disorder varies from person to person depending upon signs and symptoms seen in each patient.

Type-V-Mucopolysaccharidosis

Mucopolysaccharidosis type-5 (MPS-5) is the disorder mainly occurring in males and it is the disorder of the metabolism of carbohydrates.

It is classified based on the severity of disease as:

  • Mild Muco-PS-II (Attenuated)
  • Severe Muco-PS-II

This disorder has frequent progression. The people suffering from severe types of MPS-II can hardly live 10-20 years of age.

Causes of Muco-PS-5

MPS-5 is caused by the mutations occurring in the IDS gene. This disorder has X-linked inheritance.

Sign and symptoms

 The sign and symptoms of MPS-5 include the following:

  • Enlarged spleen.
  • Enlarged liver.
  • Hearing loss.
  • Heart deformities.
  • Joint diseases.
  • Blockage of heart valves.

 Diagnosis of Muco-PS-5

Testing of the MPS-5 can be done by testing the relative of an infected patient to determine the causes of this disorder/mutation.

In case if no relative is available for testing, then sequence analysis is done which requires a blood sample & process of the IDS gene for looking at the errors. In case if the sequence analysis fails to look for mutation, then genetic tests are used to detect mutations that cause MPS-5

Treatment of Muco-PS-5

For the treatment of MPS-5 disorder, Idursulfase is manufactured by FDA approval. This drug has been shown to improve the heal           

Type-VI-Mucopolysaccharidosis

It is also known as Maroteaux-Lamy syndrome or Hurler syndrome. It is a metabolic disorder in which a progressive multisystem is involved. This disorder is associated with arylsulfatase B (ASB) deficiency, it results in the accumulation of dermatan sulfate.

Causes of Muco-PS VI

It is caused by the ARSB gene’s mutation which is present on chromosome number 5 (5q13-5q14).

Symptoms of Muco-PS VI

All people with MPS-VI may not show all the symptoms given below:

  • Abnormal bones
  • Chronic middle ear diseases
  • Affected facial appearance
  • Short stature
  • Dwarfism
  • Abnormal arms and legs development

 Diagnosis of Muco-PS-VI

 For the diagnosis of MPS-VI disorder; healthcare professionals analyze the medical history of patients, symptoms of the disease, and laboratory tests. Genetic Testing Registry (GTR) gives sufficient information about the genetic tests of this disease.

Treatment of Muco-PS-VI

The medication/treatment of MPS-VI should be approved first by the Food and Drug Administration (FDA). N-acetylgalactosamine-4-sulfatase and recombinant humans (Nagla zyme) in the drugs are often involved to treat the MPS-VI disorder.

Type-VII-Mucopolysaccharidosis

It is called sly syndrome. It is a rare genetic disease in which the glycosaminoglycans are accumulated in the connective tissues, which results in the severity of the disorder. 

 Types of Muco-PS-VII

 On the basis of the location, this disorder has the following types:

  1. Congenital and genetic MPS-VII
  2. Eyes diseases MPS-VII
  3. Metabolic disorders MPS-VII

Causes of Muco-PS-VII

It is caused due to the mutations of the GUSB gene which causes β-D-glucuronidase deficiency and results in the accumulation of glycosaminoglycans.

Symptoms of Muco-PS-VII

  • Breakage of lumbar vertebrae
  • Abdominal disorders
  • Ascites
  • Coarse facial appearance
  • Joint restriction
  • Short stature
  • Intellectual disability
  • Pulmonary infections
  • Corneal clouding

Differential diagnosis

The differential diagnosis refers to the curation and priorly identification of the related diseases to that of Mucopolysaccharidosis depending on initial symptoms.

Treatment of Muco-PS-VII

Vestronidase alfa-vibe (Meshea) drug is commonly used for treating MPS-VII disorder.

Therapeutic curation of Mucopolysaccharidosis

Treatment of Mucopolysaccharidosis involves specialized learning programs, educational approaches for development delays, replacement as needed, physical therapy, orthopedic surgery, cardiac valve, and many other treatments.

The treatments devised for the mucopolysaccharidosis include physical and occupational therapy, hydrocephalus shunting like a tonsillectomy, and adenoidectomy processes. Idursulfase enzyme replacement during therapy.

The United States and European Union approved the Iduronate 2- sulfatase, a recombinant form of a human, in individuals having slowly progressing and severing of the disease. Medical treatments for the Mucopolysaccharidosis type 3,7, and 9 are supportive and also thought to improve the life quality of affected patients.

The walking and climbing ability of the patient suffering from Mucopolysaccharidosis type 6 can be improved by galsulfase (Nagla zyme) enzyme therapy. Moreover, it also reduces the urine glycosaminoglycan levels in the following patients.

 

Leave a Comment