Morquio syndrome life expectancy

What Is Morquio Syndrome?

This rare disease, also called MPS IV, prevents the body from breaking down certain sugar molecules.

Morquio syndrome is a rare, inherited metabolic disorder that most often affects the skeleton.

Also known as MPS IV, Morquio syndrome is part of a group of diseases called mucopolysaccharidosis (MPS).

MPS is defined by the body’s inability to break down large sugar chains called glycosaminoglycans (formerly known as mucopolysaccharides).

As a result, these molecules build up in the body and interfere with cell function.

Prevalence

It’s unknown how many people are affected by MPS IV.

Some estimates place the rate at about 1 in 210,000 people, according to a case report in the journal Joint Bone Spine.

The prevalence of the disorder also varies greatly by population.

For instance, it may occur in as many as 1 in 43,261 births among the Turkish population living in Germany, but in as few as 1 in 1,505,160 births in Sweden, according to a 2010 article in the Orphanet Journal of Rare Diseases.

Morquio affects males and females equally, and no ethnic group — broadly speaking — appears to have an increased risk for the disorder.

Types and Causes of Morquio Syndrome

There are two forms of Morquio syndrome: Type A and Type B.

Morquio A syndrome, or MPS IVA, results from a deficiency in the enzyme galactosamine (N-acetyl)-6-sulfatase (GALNS).

Morquio B syndrome (MPS IVB), which is rarer and less severe than MPS IVA, results from a deficiency in the enzyme beta-galactosidase.

Without either of these enzymes, the body cannot break down certain glycosaminoglycans, particularly keratan sulfate.

Morquio syndrome is an autosomal recessive trait, meaning that you can only develop the disorder if you inherit two mutated genes — one from your mother and one from your father.

Neither parent will likely show any signs or symptoms of the condition.

Symptoms and Complications

Glycosaminoglycans play an important role in building healthy bone, cartilage, corneas, skin, and connective tissue, including tendons and ligaments.

People with Morquio syndrome may experience issues with any of these body parts.

Symptoms, which usually begin between ages 1 and 3, may include:

  • Short stature with a long torso
  • Abnormal bone and spine development, including a curved spine (severe scoliosis)
  • Bell-shaped chest, with ribs that flare out at the bottom
  • Unusually flexible joints (hypermobile joints, also known as being double-jointed)
  • Knock-knees, or knees that angle inward and touch each other when the legs are straight
  • Teeth spaced widely apart
  • Abnormally large head (macrocephaly)
  • “Coarse” facial features, such as a bulging forehead
  • Cloudy vision
  • Heart valve issues and heart murmur
  • Enlarged liver

Over time, MPS IV may cause serious complications, including:

  • Spinal cord damage, which may result in paralysis
  • Blindness
  • Breathing problems and narrowed airways, which may cause frequent upper respiratory infections
  • Heart failure
  • Hearing impairment

Unlike some other types of MPS, Morquio syndrome doesn’t appear to cause intellectual disabilities.

Morquio Syndrome Diagnosis and Treatment

Diagnosis of Morquio syndrome typically begins with a physical examination, which can reveal various telltale signs of the disorder.

If you have signs or symptoms of MPS, your doctor will likely order a urine test to see if you have high levels of glycosaminoglycans.

Additional culture tests can detect unusual enzyme activity, and genetic tests (using saliva or blood) can reveal mutations indicative of MPS IV.

There is no cure for Morquio syndrome, and treatment is limited to supportive care of symptoms.

For example, physical therapy and surgical procedures, such as spinal fusion, may help with scoliosis and other bone and muscle issues.

In 2014, the Food and Drug Administration (FDA) approved the drug Vimizim (elosulfase alfa) for the treatment of MPS IVA.

Vimizim provides the body with the GALNS it’s missing, helping to improve physical endurance.

Morquio syndrome can significantly shorten a person’s lifespan due to spinal cord compression and breathing complications.

People with severe cases of MPS IV may only live into their twenties or thirties, and even people with mild cases don’t often live beyond age 60, according to a 2013 study in the journal Molecular Genetics and Metabolism.

Morquio syndrome: An inherited error in carbohydrate metabolism that results in mucopolysaccharide accumulation and severe skeletal defects. The defects are present at birth and include severe deformity of the spine and chest, short neck, loose and enlarged joints, and irregular ends of the long bones. The disorder is inherited in an autosomal recessive manner.

To give a synopsis of the disease: There is severe growth retardation (adult height 82 to 115 cm); the skull is unusually thick and dense; there are corneal opacities (clouding of the eyes) and hearing loss. The liver is slightly enlarged. There are multiple abnormalities of the spine (platyspondyly, odontoid hypoplasia, cervical subluxation and cervical myelopathy). The chest is pigeon-shaped (pectus carinatum). There is joint laxity and knock knees (genu valgum) and hip deformity (dysplasia). The intelligence is normal. (In other words, there is no tendency to mental retardation.) There are multiple abnormal lab findings (galactosamine-6-sulfatase deficiency in fibroblasts and amniocytes, keratan sulfaturia that decreases with age, and metachromasia of white blood cells and fibroblasts). The error in carbohydrate metabolism is a deficiency of the enzyme galactosamine-6-sulfatase. Enzyme replacement therapy has not been effective to date. Prenatal diagnosis is feasible by amniocentesis. As mentioned, the inheritance is autosomal recessive, meaning that the parents who seem normal each carry one Morquio gene and their boys and girls each run a 1 in 4 (25%) risk of receiving both of the parental Morquio genes and having the disease. The Morquio gene is located on chromosome 16 (in chromosome subband 16q24.3).

The condition was first described, simultaneously and independently in 1929, by Luis Morquio in Montevideo, Uruguay, and by JF Brailsford in Birmingham, England. They both recognized the occurrence of corneal clouding, aortic valve disease, and urinary excretion of keratosulfate. Morquio observed the disorder in 4 sibs in a family of Swedish extraction and, to further compound the international melange, reported his observations in French (Sur une forme de dystrophie osseuse familiale. Bull. Soc. (Pediat. Paris 27: 145-152, 1929). The disease should be called Morquio-Brailsford (or the reverse) syndrome, but this is rarely done. However, Morquio syndrome is sometimes called by its biochemical name — Mucopolysaccharidosis Type IV. (MPS IV)

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Morquio’s Syndrome: A Case Report of Two Siblings

Abstract

Morquio syndrome or MPS IVA is a rare type of lysosomal storage disease associated with highly specific dental abnormalities. We present two siblings with enamel hypoplasia and skeletal abnormalities. A diagnosis of mucopolysaccharidosis type IVA was reached based on the clinical, radiographic, and dental findings of the patients. The dental findings are useful diagnostic aid for the early diagnosis of this debilitating disorder.

1. Introduction

Glycosaminoglycans (GAGs), formerly known as mucopolysaccharides, are long-chained carbohydrates that are vital for the formation of bone, cartilage, tendons, corneas, skin, and connective tissue. The deficiency of lysosomal enzymes required for the metabolism of the various mucopolysaccharides results in the accumulation of the respective substrate in the cells, leading to progressive cellular damage and clinic pathological changes. Mucopolysaccharidosis (MPS) is comprised of at least seven recognized phenotypes that are assigned by numbers and eponyms.

2. Case Report

Two siblings, a 13-year-old girl (case , Figures 1(a)–1(d)) and a 10-year-old boy (case , Figures 2(a)–2(d)) of normal intelligence had come to Chettinad Dental College and Research Institute, Chennai, with a complaint of decayed teeth. The physical appearances were similar, characterized by short stature, short neck, protuberant chest, scoliosis, and a waddling gait. Their facial feature presented frontal bossing and flat nasal bridge. The history revealed that the patients had pain in the hip region on walking that subsides at rest. The parents did not belong to different ethnicity. They had a nonconsanguineous marriage and a family history free from any skeletal disorder. On oral examination, exposed teeth with sharp cusps and rough enamel texture were found (Figures 1(a), 1(b), 2(a), and 2(b)). The orthopantomograph showed thin hypoplastic enamel of normal radiodensity (Figures 1(c) and 2(c)).

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(d) Figure 1 (a), (b) Spade-shaped incisors, pointed cusps, and spacing between teeth in case . (c) Orthopantomograph showing thin enamel with normal radio density. (d) Spinal radiographs revealing kyphoscoliosis and tongue-like projections from anterior surface of vertebral bodies in case .
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(b)
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(d) Figure 2 (a), (b) Spade-shaped incisors, pointed cusps, and spacing between teeth in both maxillary and mandibular teeth in case . (c) Orthopantomograph showing thin enamel with normal radio density. (d) Pelvic radiograph showing shallow acetabula and square-shaped femoral head in case .

A multispecialty approach was adopted and medical examination of all major systems revealed no dysfunctional changes. However, the orthopedic and radiographic evaluation indicated gross skeletal deformity. The hand-wrist radiograph showed proximally narrow metacarpals. The anteroposterior view of the spine expressed curvature of the thoracolumbar vertebral segment. The lateral spinal view revealed anterior beaking of the vertebral body (Figure 1(d)). The pelvic view radiograph revealed an irregularly outlined square-shaped head of the femur and coxa valga defect (Figure 2(d)).

A diagnosis of mucopolysaccharidosis type IVA was reached based on the clinical, dental, and radiographic findings of the patients. The diagnosis would need to be confirmed by analysis of GALNS enzyme activity and molecular genetic testing of GALNS gene. Unfortunately, parents’ consent could not be obtained for this analysis.

3. Discussion

Mucopolysaccharidosis type IV (MPS type IV) is a rare disorder which presents with a number of musculoskeletal defects. The clinical condition was first described independently in 1929 by Morquio and Brailsford. Matalon et al. in 1974 identified the deficiency of enzyme N-acetyl-galactosamine-6-sulfatase causing intracellular accumulation of keratan sulfate responsible for Morquio’s syndrome type IVA . MPS type IVB is due to deficiency of beta-galactosidase . A non keratan sulfate excretion variety is labeled as MPS type IV C .

The parents did not belong to different ethnicity, yet they were not consanguineously related (first cousins, double first cousins, second cousins, double second cousin, or uncle niece relationship) . Morquio patients usually do not present with any clinical signs or symptoms until the end of first year of life, but, as the age advances, they show signs of muscular atrophy, pectus carinatum, and knock knee deformity . Obvious symptoms such as waddling gait and dwarfism due to dorsilumbar kyphoscoliosis can be observed at an earlier age . Atlantoaxial subluxation and spinal cord compression especially in the upper cervical region are frequently noted. This is a sequela of odontoid dysplasia which is a major complication of MPS type IV . The later manifestations include corneal opacity, deafness, hypermobility of joints, cardiac abnormalities, quadriplegia and respiratory paralysis .

GAGs and proteoglycans provide the extracellular polyanionic macromolecules for the biomineralization process of several biologic systems. GAGs regulate the enamel maturation during the transitional and maturation stage of amelogenesis. Typical dental changes are characterized by surface pitting and thin hypoplastic enamel resulting in altered shape and discoloration . The maxillary anterior teeth are widely spaced and the posteriors are occlusally tapered with pointed cusps . Enamel hypoplasia is a prominent feature in all forms of MPS type IVA. It is absent in MPS type IVB and MPSIVC. Thus, dental findings can be an important diagnostic aid for MPS type IVA . GAGs serve as a matrix for anchoring amelogenin at the enamel dentinal junction so that a close bond is established between enamel and dentine . Lack of sulfatase enzyme would remove the GAGS from dentinal tubule site which can cause lack of integration at enamel dentinal junction. Mineralization of enamel starts in the secretory stage of formation of enamel. Thickening of enamel crystallites to a preferred degree of orientation occurs in the maturation stage. Thus, texture of enamel is determined at both secretory and maturation stages. This could be the possible reason for rough enamel surface being noted .

Inclination of the distal ends of the radius and ulna towards each other, hand bones being short, and squat help in radiological diagnosis. Convergence of proximal surfaces of metacarpals gives a “bullet-”shaped appearance . Other findings which are observed in the present cases include coxa valga defect, odontoid hypoplasia, platyspondyly, and anterior beaking of the vertebral bodies. The pelvic deformity is characterized by short and square iliac wings associated with flat acetabula roof . The anteroposterior spinal radiograph features thoracolumbar kyphoscoliosis as seen in the present case.

Diagnostic methods available are blood and urine analysis to quantify the keratan sulfate level, direct enzyme assay in leukocytes or fibroblasts, and the wide range of radiographic views to demonstrate the skeletal abnormalities. Although the elevated urinary keratan sulfate is diagnostic of MPS, mucopolysaccharide excretion reduces with age and cases of Morquio with absence of excessive keratan sulfate in the urine have also been reported . Odontoid hypoplasia or dysplasia and spinal cord compression are the most consistent features in Morquio’s syndrome. A prenatal diagnosis for the disorder is possible by performing amniocentesis or chorionic villi sampling when there is a family history of Morquio’s syndrome. The diagnosis has to be confirmed with GALNS enzyme activity and molecular genetic testing of GALNS gene . In the present case, the children are born out of a nonconsanguineous marriage and no family members are affected. The final diagnosis is based on clinical, radiographic, and dental findings.

In conclusion, MPS IVA is a rare type of mucopolysaccharidosis associated with highly specific dental abnormalities. As there is no cure for Morquio’s syndrome, periodic monitoring and intervention are mandatory. Bone marrow transplant and enzyme replacement therapy (ERT) have been used with some success. This case illustrates the importance of systemic evaluation and inclusion of MPS type IVA in the differential diagnosis of enamel hypoplasia. As both the primary and permanent dentitions are affected, an early diagnosis is possible even in the clinically atypical cases. Early systemic evaluation and follow-up will help in improving the quality of life of the patients.

Competing Interests

There are no competing interests.

Brothers with Morquio syndrome to Try Experimental Treatment in Toronto

While most of those trips over the past decade have been to deal with the ongoing problems, the past two years have been spent trying to find a remedy for their deteriorating condition.

The experimental treatment involves a new drug called vimizim. It is meant to replace the enzymes they’re missing, which break down complex sugars in their body. It’s a six-hour treatment once a week they’ve undergone for the past 121 weeks, but it’s finally working.

“I’ve noticed big changes in them; how they feel. They’re not falling asleep like they used to. They’re breathing tests are better,” Braun says.

Five other patients in Toronto are on the drug and many more across Canada and the U.S. are trying it.

“What we’ve seen in the research trials is that it has improved mobility, endurance and energy levels in participants. It has also decreased the excess sugars in the body and hopefully will slow down the progression of the disease,” says Julian Raiman, a metabolic geneticist at The Hospital for Sick Children.

Vimizim is not a cure, but it’s hopefully buying time for Zane and Luke. The life expectancy for Morquio patients is between 20 and 40 years.

“It’s slowing the progression of our disability down. It’s not really helping us, but keeping our problems to a minimum,” says Lucas

Approval for the drug is now in the hands of Health Canada and the FDA. It could take more than three years for that approval. The boys will stay on the drug until a government decision is made.

“I don’t want anyone to go through what I’ve gone through for the past 12 years,” says Zane. I couldn’t imagine what it would be like right now to be sitting in a wheelchair doing nothing. I can’t imagine that.”

Neither can their mom.

“I’d drive to the moon and back if it meant one more day with you. I think I have put that many miles on the van. But if it means one more day. That’s what we’re doing it for. We’d like other families with Morquio to have the same opportunities we’ve had, too.”

Read more at this article’s source.

Morquio Syndrome

Morquio syndrome is a rare genetic condition that leads to short stature, bone abnormalities, and other medical problems.

What Are the Signs & Symptoms of Morquio Syndrome?

Signs of Morquio (MORE-kee-oh)

usually begin around a child’s first birthday. The signs can vary but often include:

  • short stature
  • curved spine (scoliosis or kyphosis)
  • “hypermobile” joints (joints that are more flexible than normal)
  • knock-knees
  • a chest that juts out (pectus carinatum)
  • misshapen arms and legs
  • widely spaced teeth
  • problems with the spine and spinal cord that can affect walking and breathing
  • liver enlargement
  • hearing problems
  • vision problems
  • heart problems

Morquio syndrome is progressive. This means that it gets worse over time.

What Causes Morquio Syndrome?

In Morquio syndrome, an

is either missing or the body doesn’t make enough of it. The missing enzyme breaks down sugars (called mucopolysaccarides) that help build bones, , corneas, skin, and connective tissue. When the sugar breaks down, the body can get rid of it.

But in Morquio syndrome, the sugar builds up in blood, cells, and

, progressively damaging the body. The less enzyme there is, the faster Morquio syndrome progresses.

Other types of disorders also do not break down mucopolysaccarides normally. This group of disorders is called mucopolysaccharidosis (MPS). Morquio syndrome is also called MPS IV.

Who Gets Morquio Syndrome?

Morquio syndrome is a genetic condition. It is passed down in families through their genes. For someone to have Morquio syndrome, they need to get the specific gene from their mother and father.

How Is Morquio Syndrome Diagnosed?

To diagnose Morquio syndrome, doctors start by asking questions and doing an examination. Testing usually includes:

  • blood tests and urine (pee) tests to look at enzyme activity
  • genetic testing
  • imaging studies like X-rays and MRIs
  • echocardiogram to check the heart
  • hearing tests and vision tests

How Is Morquio Syndrome Treated?

There’s no cure for Morquio syndrome. But treatments can help improve the quality of life for those who have it. These can include:

  • enzyme replacement through an IV (into a vein) line
  • surgery

What Else Should I Know?

Medical researchers are looking for ways to help people with Morquio syndrome. They’re looking into:

  • enzyme replacement therapy
  • gene therapy to replace genes that make the needed enzymes
  • bone marrow transplant to replace cells with missing or lacking enzyme with normal cells

Where Can We Get Help?

If your child has been diagnosed with Morquio syndrome, you may have a lot of strong feelings. Your child will need lifelong care and this can feel overwhelming. Online resources can help you find information and connect with other families who have children with Morquio syndrome.

Find help at:

  • The National MPS Society
  • Morquiosity

You may also want to meet with a genetic counselor. This will help you understand the risk of having another child with Morquio syndrome.

Looking Ahead

Because Morquio syndrome is a lifelong condition, your child will need your support. You can help by:

  • teaching your child about Morquio syndrome
  • taking your child to all medical appointments
  • keeping a written record of your child’s symptoms, treatments, and doctor visits
  • taking care of yourself so you can care for your child

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