Maroteaux–Lamy syndrome, or Mucopolysaccharidosis Type VI (MPS-VI), is an inherited disease caused by a deficiency in the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

arylsulfatase B (ARSB). ASRB is responsible for the breakdown of large sugar molecules called glycosaminoglycans (GAGs, also known as mucopolysaccharides). In particular, ARSB breaks down dermatan sulfate and

chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars ( N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have ov ...

. Because people with MPS-VI lack the ability to break down these GAGs, these chemicals build up in the

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pr ...

s of cells. MPS-VI is therefore a type of

lysosomal storage disease Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

Signs and symptoms

Corneal Clouding in MPS-VI (Maroteaux-Lamy Syndrome)

Unlike other MPS diseases, children with Maroteaux–Lamy syndrome usually have normal intelligence. They share many of the physical symptoms found in

Hurler syndrome 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. The inabil ...

. Maroteaux–Lamy syndrome has a variable spectrum of severe symptoms. Neurological complications include clouded

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

, thickening of the dura (the

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...

that surrounds and protects the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

and

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...

), and pain caused by compressed or traumatized nerves and

nerve root A nerve root (Latin: ''radix nervi'') is the initial segment of a nerve leaving the central nervous system. Nerve roots can be classified as: *cranial nerves, Cranial nerve roots: the initial or proximal segment of one of the twelve pairs of crania ...

s. At birth, people with Maroteaux-Lamy syndrome typically do not display any signs or symptoms. Signs are revealed early in the affected child's life, with one of the first symptoms often being a significantly prolonged age of learning how to walk. Growth begins normally, but children usually stop growing by age 8. By age 10, children often develop a shortened trunk, crouched stance, and restricted joint movement. In more severe cases, children also develop a protruding

abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the to ...

and forward-curving spine. Skeletal changes, particularly in the pelvis, are progressive and limit movement. Many children also have umbilical hernia or

inguinal hernia An inguinal hernia is a hernia (protrusion) of abdominal-cavity contents through the inguinal canal. Symptoms, which may include pain or discomfort especially with or following coughing, exercise, or bowel movements, are absent in about a third ...

s. Nearly all children have some form of heart disease, usually involving the

heart valve A heart valve is a one-way valve that allows blood to flow in one direction through the chambers of the heart. Four valves are usually present in a mammalian heart and together they determine the pathway of blood flow through the heart. A heart ...

s. Individuals with MPS VI may also experience

macrocephaly Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to ...

hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary inc ...

, distinctive coarse facial features,

macroglossia Macroglossia is the medical term for an unusually large tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties in speaking, eating, swallowing and sleeping. Macroglossia is uncommon, and usually occurs in children. ...

, dysostosis multiplex, and hepatosplenomegaly. In children with MPS VI, carpal tunnel syndrome commonly develops.

Genetics

This disorder is inherited in an autosomal recessive pattern. People with two working copies of the gene are unaffected. People with one working copy are

genetic carrier A hereditary carrier (genetic carrier or just carrier), is a person or other organism that has inherited a recessive allele for a genetic trait or mutation but usually does not display that trait or show symptoms of the disease. Carriers are, ho ...

s of Maroteaux–Lamy Syndrome. They have no symptoms but may pass down the defective gene to their children. People with two defective copies will have MPS-VI.

Diagnosis

urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and microscopic examination. Macroscopic ...

will show elevated levels of dermatan sulfate in the urine. A blood sample may be taken to assess the level of ASRB activity. Dermal fibroblast cells may also be examined for ASRB activity. Molecular genetic testing can give information about the specific mutation causing MPS-VI, but it is only available at specialized laboratories.

Treatment

The treatment of Maroteaux–Lamy syndrome is symptomatic and individually tailored. A variety of specialists may be needed. In 2005, the FDA approved the orphan drug galsulfase (Naglazyme) for the treatment of Maroteaux–Lamy syndrome. Galsulfase is an

enzyme replacement therapy Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme. ERT is availa ...

(ERT) in which the missing ASRB enzyme is replaced with a recombinant version. In addition to ERT, various procedures can alleviate the symptoms of MPS-VI. Surgery may be necessary to treat abnormalities such as carpal tunnel syndrome, skeletal malformations, spinal cord compression, hip degeneration, and hernias. Some patients may need heart valve replacement. It may be necessary to remove the tonsils and/or adenoids. Severe tracheomalacia may require surgery. Physical therapy and exercise may improve joint stiffness.

Hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary inc ...

may be treated by the insertion of a shunt to drain excess

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

. A corneal transplantation can be performed for individuals with severe corneal clouding. A

myringotomy A myringotomy is a surgical procedure in which an incision is created in the eardrum (tympanic membrane) to relieve pressure caused by excessive buildup of fluid, or to drain pus from the middle ear. A tympanostomy tube may be inserted through th ...

, in which a small incision is made in the eardrum, may be helpful for patients with fluid accumulation in the ears. Hearing aids may be useful, and speech therapy may help children with hearing loss communicate more effectively. Certain medications can be used to treat heart abnormalities, asthma-like episodes, and chronic infections associated with MPS-VI. Anti-inflammatory medications may be of benefit. Respiratory insufficiency may require treatment with supplemental oxygen. Aggressive management of airway secretions is necessary as well.

Sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many tim ...

may be treated with a CPAP or BPAP device.

Prognosis

The life expectancy of individuals with MPS VI varies depending on the severity of symptoms. Without treatment, some individuals may survive through late childhood or early adolescence. People with milder forms of the disorder usually live into adulthood, although they may have reduced life expectancy. Heart disease and airway obstruction are major causes of death in people with Maroteaux–Lamy syndrome.

Epidemiology

Males and females are affected equally. Studies have shown a birth prevalence between 1 in 43,261 and 1 in 1,505,160 live births. These numbers are likely an underestimate of the true number of cases, because

newborn screening Newborn screening (NBS) is a public health program of screening in infants shortly after birth for conditions that are treatable, but not clinically evident in the newborn period. The goal is to identify infants at risk for these conditions e ...

for MPS-VI is not widely available. Although studies have not revealed an ethnic predisposition, certain groups with a high degree of

consanguinity Consanguinity ("blood relation", from Latin '' consanguinitas'') is the characteristic of having a kinship with another person (being descended from a common ancestor). Many jurisdictions have laws prohibiting people who are related by blood fr ...

have a higher prevalence of MPS-VI. For example, one study of a population of Turkish immigrants in Germany revealed that this group had a rate of 1 in 43,261; this was approximately ten times higher than the rate of MPS-VI in non-Turkish Germans. In different populations worldwide, MPS-VI made up between 2 and 18.5% of all MPS disorders.

History

It is named after Pierre Maroteaux (1926–2019) and his mentor Maurice Emil Joseph Lamy (1895–1975), both French physicians. Isabel Bueso

Society and culture

Keenan Cahill was a

YouTuber A YouTuber is an online personality and/or influencer who produces videos on the video-sharing platform YouTube, typically posting to their personal YouTube channel. The term was first used in the English language in 2006. Influence Influe ...

with Maroteaux–Lamy syndrome. He died on December 29, 2022, following open-heart surgery two weeks earlier. Isabel Bueso, a Guatemalan woman with Maroteaux–Lamy syndrome who has been receiving treatment at

UCSF Benioff Children's Hospital UCSF Benioff Children's Hospital is a children's hospital system in San Francisco, California, subordinate to the University of California, San Francisco. It has four campuses: the Parnassus Campus, the Mount Zion Campus, and the Mission Bay Campu ...

, was at risk of deportation from the United States after the Trump Administration ended the deferred action program in August 2019. In December 2019, she was granted another deferral of two years. In December 2022, she was granted permission to stay in the U.S. permanently.

References

External links

{{DEFAULTSORT:Maroteaux-Lamy Syndrome Proteoglycan metabolism disorders Rare genetic syndromes