About mucolipidosis iii

What is mucolipidosis iii?

General Discussion

Pseudo-Hurler polydystrophy (mucolipidosis type III) is a rare genetic metabolic disorder characterized by a defective enzyme known as UPD-N-acetylglucosamine-1-phosphotransferase. This defective enzyme ultimately results in the accumulation of certain complex carbohydrates (mucopolysaccharides) and fatty substances (mucolipids) in various tissues of the body. The symptoms of this disorder are similar, but less severe than those of I-cell disease (mucolipidosis type II) and may include progressive joint stiffness, curvature of the spine (scoliosis), and/or skeletal deformities of the hands (e.g., claw-hands). Growth delays accompanied by deterioration of the hip joints typically develop in children with pseudo-Hurler polydystrophy. Additional symptoms may include clouding of the corneas of the eyes, mild to moderate coarseness of facial features, mild mental retardation, easy fatigability, and/or heart disease. Pseudo-Hurler polydystrophy is inherited as an autosomal recessive trait. This disorder belongs to a group of diseases known as lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that break down certain fats and carbohydrates. Defective lysosomal enzymes associated with pseudo-Hurler polydystrophy leads to the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body.

What are the symptoms for mucolipidosis iii?

Small hands with abnormally long fingers and overlapping fingers symptom was found in the mucolipidosis iii condition

In most cases, children with pseudo-Hurler polydystrophy do not exhibit symptoms until 2-4 years of age. Specific symptoms and rate of progression may vary from case to case although the disorder is often slowly progressive.

Initial symptoms may include stiffness of the hands and shoulders. In some cases, claw-like deformities of the hands may occur. These symptoms may progress to cause difficulty with specific tasks (e.g., getting dressed). Eventually, carpal tunnel syndrome may develop. Carpal tunnel syndrome is a neurological disorder characterized by compression of the median nerve, which passes through the carpal tunnel inside the wrist (peripheral nerve entrapment). Symptoms of this disorder affect the hand and wrist and may include pain, numbness, loss of feeling in the fingertips, and/or unusual sensation such as burning or “pins and needles.”

Additional symptoms associated with pseudo-Hurler polydystrophy may include side-to-side curvature of the spine (scoliosis), degeneration of the hip, joints that are permanently fixed in a bent or flexed position (contractures), and short stature. Progressive degeneration of the hip and joint contractures may cause difficulty walking or force affected individuals to walk with a characteristic waddling gait.

Affected children may also develop coarse facial features, clouding (opacity) of the surface of the eye (cornea), abnormalities affecting the nerve-rich membrane (retina) lining the eyes (mild retinopathy), and irregular curvature of the cornea (hyperopic astigmatism).

Although many children with pseudo-Hurler polydystrophy have normal intelligence, some may develop mild intellectual disability or learning disabilities. In some cases, affected children develop aortic insufficiency, a cardiovascular condition in which the aortic valve weakens preventing the valve from shutting and allowing backflow of blood from the major artery of the body (aorta) into one of the chambers of the heart (left ventricle). Symptoms of aortic insufficiency may include Palpitations, Fatigue, Shortness of breath, and Chest pain.

What are the causes for mucolipidosis iii?

Pseudo-Hurler polydystrophy is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Investigators have determined that pseudo-Hurler polydystrophy is caused by disruption or changes (mutations) in the UDP-N-acetylglucosamine-1-phosphotransferase gene known as GNPTAB located on the long arm of chromosome 4 (4q21-q23). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 4q21-q23” refers to bands 21-23 on the long arm of chromosome 4. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Investigators have determined that variant pseudo-Hurler polydystrophy (mucolipidosis IIIC) results from mutations in the GlcNAc-phosphotransferase -subunit gene located on chromosome 16.

The symptoms of pseudo-Hurler polydystrophy result from a defective enzyme known as UPD-N-acetylglucosamine-1-phosphotransferase. Due to this defect, certain lysosomal enzymes fail to reach their proper destination (i.e., lysosomes). Lysosomes are particles bound in membranes within cells that break down certain fats and carbohydrates. Lysosomal enzymes are mistakenly secreted outside cells resulting in elevated lysosomal enzymes in the serum and fluids of affected individuals. The failure of lysosomal enzymes to reach the lysosomes within cells results in the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells, which, in turn, results in the symptoms of the disorder.

What are the treatments for mucolipidosis iii?

There is no definitive treatment for pseudo-Hurler polydystrophy. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedic surgeons, cardiologists, eye specialists, and other healthcare professionals may need to systematically and comprehensively plan an affected child's treatment.

Surgery may be used to treat a variety of symptoms associated with pseudo-Hurler polydystrophy including carpal tunnel syndrome, skeletal malformations, and degeneration of the hip. Corneal transplantation has been performed with mixed results. Physical therapy and exercise may improve joint stiffness. Heart valve replacement may be necessary in some cases.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

What are the risk factors for mucolipidosis iii?

There are several different types of mucolipidosis III (MLIII), each with its own set of symptoms and risk factors. The most common type is known as Sanfilippo type B (or Type B). There are also Sanfilippo types A and C, but these are much less common than Type B.

  • The risk factors for MLIII include having a family member who has been diagnosed with it or another type of mucolipidosis.
  • Other risk factors include having a child with a genetic disorder such as cystic fibrosis or Down's syndrome; being adopted from an orphanage in India; living near one's birth country; and having relatives who live in areas where malaria is common.
  • In some cases, people with mucolipidosis III don't show symptoms until they're teenagers or adults. In other cases, infants are born with the condition and start showing symptoms right away.
  • Symptoms include abnormal facial features like a small chin and wide-set eyes, poor growth and development (which means they may not reach normal height), abdominal swelling due to fluid build-up around their intestines and organs like the liver or spleen (which causes pain) and a condition called corneal clouding, which causes vision problems.
Symptoms
A wide range of facial features, including a large forehead and a small chin, as well as an underdeveloped jawbone,Curved arms and legs,Small hands with abnormally long fingers and overlapping fingers,Abnormally large internal organs, such as the stomach, liver, spleen or kidneys (an enlarged heart may be present at birth but will shrink later in life)
Conditions
Genetic variations disrupt the normal activity of lysosomes in human cells
Drugs
Steroids,Enzyme replacement therapy (ERT)

Is there a cure/medications for mucolipidosis iii?

There is no cure for mucolipidosis III. Doctors can treat symptoms, but not the disease itself, which means it will get worse over time.

  • The most common treatments are steroids and enzyme replacement therapy (ERT). ERT replaces enzymes that are missing due to the disease so that digestion is normal. Steroids help reduce inflammation caused by mucolipidosis III.
  • Enzyme replacement therapy is a treatment that provides the missing enzymes that the body needs to break down certain fats and sugars, which allows them to be absorbed by the body.
  • The patient then has their blood drawn and the enzymes are isolated from it, then injected into their body through an IV. This treatment can be done multiple times per week, depending on how often it's needed.
  • It's important to note that enzyme replacement therapy does not cure mucolipidosis III—it treats it.
  • But for many patients, this treatment is life-changing: they can lead more normal lives, go to school or work outside of the home, participate in sports and other physical activities with their friends and family members without worrying about getting sick or passing out because of low blood sugar levels or increased fatigue due to organ damage caused by lack of adequate nutrition absorption by organs like heart muscles (cardiomyopathy).
  • Doctors may also use medications to slow down or stop seizures and control pain caused by this condition.
Symptoms
A wide range of facial features, including a large forehead and a small chin, as well as an underdeveloped jawbone,Curved arms and legs,Small hands with abnormally long fingers and overlapping fingers,Abnormally large internal organs, such as the stomach, liver, spleen or kidneys (an enlarged heart may be present at birth but will shrink later in life)
Conditions
Genetic variations disrupt the normal activity of lysosomes in human cells
Drugs
Steroids,Enzyme replacement therapy (ERT)

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