is hurler syndrome fatal

Full Answer

What is Hurler syndrome?

Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS1; see this term), a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy. Epidemiology.

What is the life expectancy of someone with Hurler syndrome?

A British study from 2008 found a median estimated life expectancy of 8.7 years for patients with Hurler syndrome. In comparison, the median life expectancy for all forms of MPS type I was 11.6 years. Patients who received successful bone marrow transplants had a 2-year survival rate of 68% and a 10-year survival rate of 64%.

Is Hurler–Scheie syndrome a genetic disease?

This information comes from the Human Phenotype Ontology (HPO) Hurler–Scheie syndrome is a genetic disease, which means that it is caused by one or more genes not working correctly. What is a gene?

Is there a cure for Hurler syndrome?

There is currently no cure for Hurler Syndrome. Enzyme replacement therapy with iduronidase (Aldurazyme) may improve pulmonary function and mobility. It can reduce the amount of carbohydrates being improperly stored in organs.

What happens to a person with Hurler syndrome?

Hurler syndrome is an inherited condition caused by a faulty gene. Children with Hurler syndrome lack an enzyme that the body needs to digest sugar. As a result, undigested sugar molecules build up in the body, causing progressive damage to the brain, heart, and other organs.

What is the life expectancy of someone with Hurler syndrome?

Children with Hurler syndrome can suffer from skeletal abnormalities, cognitive impairment and developmental delays, heart valve disease and respiratory problems, enlarged organs, macrocephaly, severely short stature, corneal clouding, endocrine problems and a life expectancy under 10 years of age.

Is Hurler syndrome life-threatening?

Hurler syndrome is the most severe form of mucopolysaccharidosis type I, a hereditary lysosomal storage condition. Cells can't break down sugar molecules, which affects how they function. Symptoms are life-threatening, target your bones and organs, and could cause issues with cognitive development.

Can you live with Hurler syndrome?

Without treatment, patients with Hurler syndrome experience multisystem manifestations including mental retardation, skeletal deterioration, severe cardiopulmonary disease, hepatosplenomegaly, visual impairment, and deafness, usually leading to death within the first decade of life (Neufeld and Muenzer 2001).

How common is Hurler syndrome?

The incidence of Hurler syndrome is approximately 1 in 100,000 births. [1] Male and female children are equally affected. All races and ethnicities are at risk of inheriting the disease.

Can Hurler syndrome be prevented?

BMT, also known as a bone marrow transplant or blood stem cell transplant, can stop the disease from causing more damage.

What causes Hurler?

Hurler syndrome is caused by a variation in the IDUA gene, which contains the instructions for the production of a specific enzyme known as alpha-L-iduronidase. This specialized protein is normally found in the lysosomes of cells, where it helps to break down complex sugars called glycosaminoglycans (GAGs).

How long do people with MPS live for?

The life expectancy of these individuals is 10 to 20 years. Individuals with mild MPS II also have a shortened lifespan, but they typically live into adulthood and their intelligence is not affected. Heart disease and airway obstruction are major causes of death in people with both types of MPS II.

What is the treatment for Hurler syndrome?

Stem Cell Transplant: Another treatment available for MPS I is a bone marrow transplant, which puts normal cells in the body that will manufacture the missing enzyme. However, many children with Hurler syndrome have heart disease and are not able to go through the chemotherapy required for the transplant.

How is Hurler syndrome diagnosed?

Exams and Tests ECG. Genetic testing for changes to the alpha-L-iduronidase (IDUA) gene. Urine tests for extra mucopolysaccharides. X-ray of the spine.

Are there prenatal tests to help detect Hurler syndrome?

Prenatal testing of the fluid that surrounds the baby (amniocentesis) or of a tissue sample from the placenta (chorionic villus sampling) can verify if your unborn child carries a copy of the defective gene or is affected with the disorder.

Is MPS curable?

There is no cure for MPS 1, however, there are effective treatments that are proven to slow the progression of disease. Hematopoietic stem cell transplantation (HSCT) can help some patients who have the severe form of the disease, and is generally recommended within the first 1-2 years of life.

How is Hurler syndrome inherited?

This condition is genetic and is inherited in an autosomal recessive pattern, which means that an affected child has received one defective copy of the IDUA from each parent.

What is Hunter syndrome disease?

Hunter syndrome is a very rare, inherited genetic disorder caused by a missing or malfunctioning enzyme. In Hunter syndrome, the body doesn't have enough of the enzyme iduronate 2-sulfatase.

What is Sanfilippo Syndrome?

Mucopolysaccaridosis type III (MPS III) is a rare genetic condition that causes fatal brain damage. It is also known as Sanfilippo syndrome and is a type of childhood dementia. MPS III is caused by a lack of an enzyme that normally breaks down and recycles a large, complex sugar molecule called 'heparan sulphate'.

What is Hurler syndrome?

Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS1; see this term), a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy.

What is the treatment for Hurler syndrome?

Management is multidisciplinary. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with Hurler syndrome under 2.5 years of age (and in selected patients over this age limit) as it can prolong survival, preserve neurocognition, and ameliorate some somatic features. HSCT should be performed early in the disease course, before developmental deterioration begins. Enzyme replacement therapy (ERT) with laronidase is recommended for all Hurler patients and is a lifelong therapy which alleviates non neurological symptoms. The early use of ERT has been shown to delay or even prevent the development of some of the clinical features of this condition. Additional management of Hurler syndrome is largely supportive, and includes surgical interventions (e.g. adenotonsillectomy, hernia repair, ventriculoperitoneal shunt, cardiac valve replacement, carpal tunnel release, spinal decompression); physical, occupational, and speech therapies; respiratory support (e.g., continuous positive pressure ventilation with oxygen supplementation); hearing aids; and medications for pain and gastrointestinal disturbances.

What is Hurler syndrome?

Hurler syndrome, also known as mucopolysaccharidosis type I (MPH I), is one of the eleven mucopolysaccharidoses (MPS) disorders. Hurler syndrome was formerly known as gargoylism. It is an inherited lysosomal disorder caused by the absence of alpha-L-iduronidase, an enzyme responsible for the degradation of glycosaminoglycans (GAGs or mucopolysaccharides). This leads to a buildup of dermatan sulfate and heparin sulfate in multiple tissues, resulting in progressive deterioration and eventually, death. This activity describes the pathophysiology, evaluation, and management of hurler syndrome and the role of the interprofessional team in the care of affected patients.

What is the most common form of Hurler syndrome?

Hurler syndrome (MPS I H): This is the most common and severe form. Patients develop symptoms shortly after birth and progress rapidly. The symptoms include developmental delay, cognitive decline, characteristic coarse facial features, joint stiffness and contractures, short stature, and cardiac and hepatic disease. Patients usually die within the first year of life. [2]

When was Hurler syndrome first described?

Hurler syndrome was first described by German pediatrician, Gertrud Hurler in 1919. It is one of the 11 disorders of the mucopolysaccharidoses (MPS). Hurler syndrome is considered as mucopolysaccharidosis type I (MPH I) and formerly known as gargoylism. In 1962, a milder form of MPS I was identified and named as Scheie syndrome.

What are the manifestations of Hurler syndrome?

Cardiac manifestations: These include cardiomyopathy, endocardial fibroelastosis, valvular regurgitation, and heart failure. GAG deposition within the blood vessels causes diffuse narrowing of the coronary arteries. Some untreated patients develop irregular lesions of the aorta. Most patients with severe Hurler syndrome die from heart failure before the age of 10.[2]  It has been recommended that patients undergo cardiac evaluation every 1 or 2 years after an initial diagnosis of Hurler syndrome.

How many births are affected by Hurler syndrome?

The incidence of Hurler syndrome is approximately 1 in 100,000 births.[1]  Male and female children are equally affected. All races and ethnicities are at risk of inheriting the disease.

Is Sly syndrome a rare disorder?

Sly syndrome (mucopolysaccharidosis type 6): This a rare disorder shares similar clinical features as Hurler syndrome. Mental retardation may be mild or absent. Hydrops fetalis is a most common presentation, and usually, patients do not survive to diagnosis.

Is Hurler Syndrome a MPS?

Hurler Syndrome is considered as MPS I. The presentation and course of the disease vary due to underlying IUDA mutations and a consequent residual degree of enzyme activity. MPS I is further subdivided into three subtypes.

How long do people with Hurler syndrome live?

A British study from 2008 found a median estimated life expectancy of 8.7 years for patients with Hurler syndrome. In comparison, the median life expectancy for all forms of MPS type I was 11.6 years. Patients who received successful bone marrow transplants had a 2-year survival rate of 68% and a 10-year survival rate of 64%. Patients who did not receive bone marrow transplants had a significantly reduced lifespan, with a median age of 6.8 years.

What is the frequency of Hurler syndrome?

Frequency. 1 in 100,0000. Hurler syndrome, also known as mucopolysaccharidosis Type IH ( MPS-IH ), Hurler's disease, and formerly gargoylism, is a genetic disorder that results in the buildup of large sugar molecules called glycosaminoglycans (GAGs) in lysosomes.

Why is Hurler syndrome called MPS IH?

Because of the communications interruptions caused by World War I , it is likely that she was unaware of his study. Hurler syndrome now refers to MPS IH, while Hunter syndrome refers to MPS II. In 1962, a milder form of MPS I was identified by Scheie, leading to the designation of Scheie syndrome.

How many births are there in Hurler syndrome?

Hurler syndrome has an overall frequency of one per 100,000. Combined, all of the mucopolysaccharidoses have a frequency of approximately one in every 25,000 births in the United States.

What is the most severe MPS I?

All three types result the absence or decreased functioning of the same enzyme. MPS-IH (Hurler syndrome) is the most severe of the MPS I subtypes. The other two types are MPS-IS ( Scheie syndrome) and MPS-IHS ( Hurler-Scheie syndrome ).

When do Hurler syndrome symptoms start?

One of the first abnormalities that may be detected is coarsening of the facial features; these symptoms can begin at 3–6 months of age. The head can be large with prominent frontal bones.

Who was the first person to describe a condition that caused the corneal clouding and mental retardation?

In 1919, Gertrud Hurler , a German pediatrician, described a syndrome involving corneal clouding, skeletal abnormalities, and mental retardation. A similar disease of "gargoylism" had been described in 1917 by Charles A. Hunter. Hurler did not mention Hunter's paper. Because of the communications interruptions caused by World War I, it is likely that she was unaware of his study. Hurler syndrome now refers to MPS IH, while Hunter syndrome refers to MPS II. In 1962, a milder form of MPS I was identified by Scheie, leading to the designation of Scheie syndrome.

What is the cause of Hurler syndrome?

Inborn Error of Energy Metabolism. Hurler syndrome is an inherited condition caused by a faulty gene. Children with Hurler syndrome lack an enzyme that the body needs to digest sugar. As a result, undigested sugar molecules build up in the body, causing progressive damage to the brain, heart, and other organs.

When do you start to see symptoms of Hurler syndrome?

Symptoms most often begin to appear between ages 3 and 8. Children with Hurler syndrome may have unusually large heads, joint stiffness, hearing and vision loss, impaired growth, and other symptoms. The medical name for Hurler syndrome is mucopolysaccharidosis type I.

What causes this disease?

Mucopolysaccharides are chains of sugar molecules used to build connective tissues in the body.

Which disease does my child have?

MPS I (Hurler-Scheie) is a continuum of severity based upon the symptoms, ranging from severe to attenuated. There is a great deal of variability of symptoms among individuals with MPS I, often making the specific designation difficult.

How common are these diseases?

Severe MPS I occurs in approximately 1 in 100,000 newborns. Attenuated MPS I is less common and occurs in about 1 in 500,000 newborns.

How is the disease inherited?

MPS I (Hurler-Scheie syndrome ) is caused by a recessive gene. There is a one in four chance with every pregnancy that the child will inherit the defective gene from each carrier parent and will be affected with the disease. There is a two in three chance that unaffected brothers and sisters of children with MPS I will be carriers.

Is there cure for MPS I?

There is no cure but treatments such as bone marrow transplantation and/or enzyme replacement therapy (ERT) can help make MPS I a more manageable disease. Aldurazyme is the first and only FDA approved ERT treatment developed through recombinant DNA technology for individuals with MPS I.

What are the complications of Hunter syndrome?

There are various complications of Hunter syndrome, such as respiratory, cardiac, nervous system, skeletal and connective tissue.

How old do you have to be to have Hunter syndrome?

The symptoms do not start at birth, but start at around the age of 2-4 years in type A and 2 years later for type B. The signs and symptoms include coarse facial features, enlarged head, flat nasal bridge, broad nose and flared nostrils, thick lips, enlarged tongue, hoarse voice, stunted growth, skeletal deformities, enlarged stomach due to hepatomegaly and splenomegaly, diarrhea or constipation, pebbled appearance of skin, Mongolian spots, joint stiffness, delayed development.

What are the consequences of neurologic complications?

Neurological Complications can significantly reduce cognition and mental development of the child. Hydocephalus can secondarily cause symptoms due to intracranial pressure, including seizures, headaches, vision and mental state of the patient. Compression of upper spinal cord leading to fatigue, and weakening of muscles lead to reduced physical activity. Nerve compression can lead to carpal tunnel syndrome. Cognitive problems can lead to hyperactivity, attention deficit, aggressive behavior, and speech and communication problems. Neurological complications develop only in severe form of Hunter syndrome that dramatically reduces the quality of life.

Is Hunter Syndrome Fatal?

The development of various complications in Hunter syndrome can be fatal. The highest amount of morbidity and mortality associated with complications in Hunter syndrome include the respiratory and cardiac complications. Respiratory complications can be highly fatal and are associated with maximum death due to obstruction of airways, difficulty in breathing and pneumonia. Mortality related to cardiac complications includes myocardial infarction and cardiac failure. Respiratory and cardiac complications lead to premature death. Patient’s life span is dramatically reduced and patients with type A MPS II die before second decade of their lives. In MPS II B, patients hardly live up to fifth or sixth decade of life and usually die earlier due to respiratory or cardiac complications, despite treatment. (1)

Overview

Signs and symptoms

Mechanisms

Genetics

Diagnosis

Treatment

Prognosis

Epidemiology