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Mucopolysaccharidosis 6

Maroteaux Lamy Syndrome

Mucopolysaccharidosis type 6 (MPS6) or Maroteaux Lamy syndrome is a rare autosomal recessive disorder characterized by the accumulation of mucopolysaccharides in connective tissues as a result of the reduced or absent activity of the lysosomal enzyme arylsulfatase B (ASB). This is a progressive disorder that affects numerous organs and tissues.

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Presentation

MPS6 can be considered as a spectrum of the disease since the clinical picture can range from mild to severe. Patients with the rapidly progressive form develop symptoms between ages 2 and 3 years. This is typically characterized by limitations in joint motion during infancy, walking disabilities in childhood as well as delayed puberty, cervical spine compression, respiratory failure, and heart failure (second or third decade). The slowly progressive variant occurs at a later onset with a diagnosis often during the second or third decade although they may experience symptoms sooner.

Numerous organs systems are involved in MPS6:

Musculoskeletal

Patients very commonly exhibit a disproportionately short stature. Major skeletal abnormalities include hypoplastic bones, hip dysplasia, pectus carinatum, genu valgum, and kyphoscoliosis. Major sequelae include spinal cord compression, degenerative joint disease [9] [10], contractures, and arthritis. The affected individuals often suffer from pain, gait difficulties, and restriction of joint movement.

Face

In severe cases, patients display prominent facial characteristics. Examples include low and flat nasal bridge, frontal bossing, gingival hypertrophy, macroglossia, and hirsutism [9] [10].

Eyes and ears

Patients may have corneal opacification which causes glaucoma and papilledema [9] [10]. Hearing loss is common and can occur due to conductive or sensorineural etiologies.

Neurologic

Carpal tunnel syndrome is a frequent complication in individuals with MPS6. Furthermore, hydrocephalus is a more severe neurologic manifestation that occurs in some patients.

Gastrointestinal

Common findings on physical exam are hepatosplenomegaly and umbilical and inguinal hernias. The latter two develop as a result of weakened abdominal muscles.

Cardiac

Patients frequently have aortic, mitral, and tricuspid valvular disease. Also, structural pathologies such as cardiomyopathy and endocardial fibroelastosis are notable defects. As a result of cardiac involvement, patients exhibit failure to thrive and experience difficulty with feeding.

Pulmonary

Storage of mucopolysaccharides causes swelling of tissues, which leads to obstruction of the airways. Patients are typically susceptible to developing obstructive and restrictive lung disease which are accompanied by complications such as recurrent pneumonia and obstructive sleep apnea (OSA).

Cognitive

Intelligence is normal in these patients.

Splenomegaly
  • Immune System Splenomegaly Macrocephaly Enlarged tongue Prominent forehead Possible coarse texture of hair Hepatomegaly and splenomegaly are often present in patients with MPS VI. Umbilical and inguinal hernias are common.[symptoma.com]
  • Macrocephaly Enlarged tongue Prominent forehead Possible coarse texture of hair Hepatomegaly and splenomegaly are often present in patients with MPS VI. Umbilical and inguinal hernias are common.[emedicine.medscape.com]
  • Less often, the spleen may also be enlarged (splenomegaly). Hernias, conditions in which the abdominal membrane or contents protrude through a weak point in the abdominal wall, are also common.[rarediseases.org]
  • Patient’s also often have enlargement of the spleen – a condition called “splenomegaly”. It is not uncommon for patients to have various types of hernias.[virtualmedstudent.com]
  • Coarse facial features, short stature, corneal clouding, hepatomegaly, and/or splenomegaly were the predominant signs and symptoms at presentation.[journals.sagepub.com]
Short Stature
  • The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease.[orpha.net]
  • [virtualmedstudent.com] Entire body system Short Stature The characteristic skeletal dysplasia includes short stature , dysostosis multiplex and degenerative joint disease.[symptoma.com]
  • Numerous organs systems are involved in MPS6: Musculoskeletal Patients very commonly exhibit a disproportionately short stature.[symptoma.com]
  • These include abnormally large head, frequent ear and respiratory infections, and short stature in children A healthcare professional can use various diagnostic tools, such as a physical exam, electrocardiogram, urinalysis (analysis of urine), and X-rays[dovemed.com]
  • Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff[glosbe.com]
Pain
  • An experiment was then carried out to see whether an injection of the missing enzyme into the hips would help the range of motion and pain.[en.wikipedia.org]
  • [medical-dictionary.thefreedictionary.com] Pain An experiment was then carried out to see whether an injection of the missing enzyme into the hips would help the range of motion and pain .[symptoma.com]
  • - A dictionary of medical eponyms Related people Maurice Emile Joseph Lamy Pierre Maroteaux A familial type of bone dysplasia marked by short-trunk dwarfism, back pain, pain in the hips, and limitation of joint movement.[whonamedit.com]
  • 2011; 49, 4: 288–293 Online publish date: 2011/08/30 Authors present a case of 38-year-old woman, of whom the first symptoms of the disease were poor exercise tolerance, increasing limitation of motion in the shoulder, elbow and hip joints and bone pain[termedia.pl]
  • Common symptoms of Maroteaux-Lamy syndrome include: Clouding of the cornea, vision loss Coarse facial features Skeletal and muscular deformities, which can be acute Abnormalities within the joints Mild to severe chronic pain Numbness, tingling Loss of[patientworthy.com]
Inguinal Hernia
  • Umbilical and inguinal hernias are common.[symptoma.com]
  • Many children also have umbilical hernia or inguinal hernias. Nearly all children have some form of heart disease, usually involving valve dysfunction.[en.wikipedia.org]
  • Other symptoms may include carpal tunnel syndrome, curvature of the spine, a frequent runny nose, inguinal hernias and hearing loss. Incidence Maroteaux-Lamy syndrome affects one in 200,000 people.[bmt.umn.edu]
  • Often these individuals also develop abnormalities of heart valves, hepatosplenomegaly and umbilical hernia or inguinal hernia.[ivami.com]
  • Umbilical and inguinal hernias are common. Growth may be normal for several years and may then stop, resulting in a final stature of 90-140 cm. A short trunk with lumbar lordosis is typically present.[emedicine.medscape.com]
Recurrent Otitis Media
  • [rarediseases.org] Recurrent Otitis Media We found ear, nose and throat manifestations in all types of MPS; in particular, recurrent otitis media was present in 30% of cases, hearing loss in 75% (mixed in 43.33%, conductive in 43.33%, sensorineural in[symptoma.com]
  • We found ear, nose and throat manifestations in all types of MPS; in particular, recurrent otitis media was present in 30% of cases, hearing loss in 75% (mixed in 43.33%, conductive in 43.33%, sensorineural in 13.33%), adenotonsillar hypertrophy in 75%[ncbi.nlm.nih.gov]
  • Recurrent respiratory infections were noted in 11 of the 27 patients (41%) and recurrent otitis media was seen in 19 (70%), all with documented conductive hearing loss and requiring pressure-equalizing tubes.[jamanetwork.com]
  • otitis media, and premature death [ 1, 2, 3, 4 ].[ojrd.biomedcentral.com]
Difficulty Walking
  • [symptoma.com] Difficulty Walking Affected individuals may develop pain, especially of the joints and hip, spinal cord compression, an abnormal manner of walking (gait), or difficulty walking .[symptoma.com]
  • Affected individuals may develop pain, especially of the joints and hip, spinal cord compression, an abnormal manner of walking (gait), or difficulty walking. Affected joints may have a limited range of motion making daily tasks difficult.[rarediseases.org]
Failure to Thrive
  • […] to Thrive As a result of cardiac involvement, patients exhibit failure to thrive and experience difficulty with feeding.[symptoma.com]
  • As a result of cardiac involvement, patients exhibit failure to thrive and experience difficulty with feeding. Pulmonary Storage of mucopolysaccharides causes swelling of tissues, which leads to obstruction of the airways.[symptoma.com]
  • Affected children may also exhibit failure to thrive and difficulty feeding. High blood pressure (hypertension) may also occur.[rarediseases.org]
Macroglossia
  • [rarediseases.org] Jaw & Teeth Macroglossia . , , , , , Source MeSH Alveolar Process Child Consanguinity Dentigerous Cyst Gingival Hyperplasia Humans Macroglossia Male Mouth Abnormalities Mucopolysaccharidosis VI Open Bite Palate, Hard Pedigree Tooth[symptoma.com]
  • The features of MPS VI include macrocephaly, hydrocephalus and macroglossia. Often these individuals also develop abnormalities of heart valves, hepatosplenomegaly and umbilical hernia or inguinal hernia.[ivami.com]
  • ., ,, ,, Source MeSH Alveolar Process Child Consanguinity Dentigerous Cyst Gingival Hyperplasia Humans Macroglossia Male Mouth Abnormalities Mucopolysaccharidosis VI Open Bite Palate, Hard Pedigree Tooth Abnormalities Tooth, Unerupted Pub Type(s) Case[unboundmedicine.com]
  • They have coarse facial and somatic features, umbilical and scrotal hernia, macroglossia, visceromegaly, disostosis multiplex and joint involvement. In most forms corneal cloudiness is seen. These symptoms usually appear during early infancy.[bhj.org.in]
  • Examples include low and flat nasal bridge, frontal bossing, gingival hypertrophy, macroglossia, and hirsutism. Eyes and ears Patients may have corneal opacification which causes glaucoma and papilledema.[symptoma.com]
Gingival Hypertrophy
  • [rarediseases.org] Gingival Hypertrophy Examples include low and flat nasal bridge, frontal bossing, gingival hypertrophy , macroglossia, and hirsutism. Eyes and ears Patients may have corneal opacification which causes glaucoma and papilledema.[symptoma.com]
  • Examples include low and flat nasal bridge, frontal bossing, gingival hypertrophy, macroglossia, and hirsutism. Eyes and ears Patients may have corneal opacification which causes glaucoma and papilledema.[symptoma.com]
  • Such characteristics include chubby faces, thickened lips due to the overgrowth of the gums (gingival hypertrophy), an unusually prominent forehead (frontal bossing), and a broad, flattened bridge of the nose.[rarediseases.org]
Heart Failure
  • [rarediseases.org] Cardiovascular Heart Failure Narrowing of the heart valves can progressively make it more difficult for the heart to pump blood and can eventually result in heart failure .[symptoma.com]
  • Narrowing of the heart valves can progressively make it more difficult for the heart to pump blood and can eventually result in heart failure.[rarediseases.org]
  • In severe cases of Maroteaux-Lamy syndrome, symptoms include mobility issues (problems walking), total absence of or delay with puberty, and heart failure in early 20s-30s.[patientworthy.com]
  • Because of the cardiac involvement, most patients with the severe forms of the disease will die of heart failure by the second or third decade. return to Inborn Errors page return to Glycosaminoglycans and Proteoglycans page Return to The Medical Biochemistry[themedicalbiochemistrypage.org]
Hepatosplenomegaly
  • [termedia.pl] Liver, Gall & Pancreas Hepatosplenomegaly Clinical findings Abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly and cardiac defects.[symptoma.com]
  • Clinical findings Abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly and cardiac defects.[medical-dictionary.thefreedictionary.com]
  • Hepatosplenomegaly is always present in Maroteaux-Lamy patients after the age of 6.[themedicalbiochemistrypage.org]
  • Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff[glosbe.com]
  • Age MPS VI is an inherited disorder that typically manifests in early childhood with retarded growth, dysostosis multiplex, inguinal or umbilical hernias, recurrent respiratory illness, hepatosplenomegaly, and coarse facial features.[emedicine.medscape.com]
Hepatomegaly
  • We report a case of Maroteaux-Lamy syndrome in a child aged 9 years whose diagnosis was suspected clinically by the combination of a dysmorphic syndrome, prominent ophthalmological signs, hepatomegaly and normal intelligence.[scopemed.org]
  • [emedicine.medscape.com] Abnormal enlargement of the liver ( hepatomegaly ) is common in individuals with Maroteaux-Lamy syndrome. Less often, the spleen may also be enlarged (splenomegaly).[symptoma.com]
  • Hepatomegaly, corneal clouding, claw-hand deformities, cardiac valve involvement, decreased pulmonary function, and sleep apnea become evident as the child ages. Respiratory infections are common.[egl-eurofins.com]
  • Macrocephaly Enlarged tongue Prominent forehead Possible coarse texture of hair Hepatomegaly and splenomegaly are often present in patients with MPS VI. Umbilical and inguinal hernias are common.[emedicine.medscape.com]
  • Abnormal enlargement of the liver (hepatomegaly) is common in individuals with Maroteaux-Lamy syndrome. Less often, the spleen may also be enlarged (splenomegaly).[rarediseases.org]
Hearing Impairment
  • Abstract Objective The aim of our study is to reflect hearing impairment of 23 children diagnosed with mucopolysaccharidosis (MPS) type I, II, III and IV.[elsevier.es]
  • The most common findings consistent with CNS involvement are mental retardation, hydrocephalus, progressive spasticity, seizures, cerebral infarction, ataxia, cervical cord compression and myelopathy, sleep apnea, optic atrophy, hearing impairment, and[ajnr.org]
Hearing Problem
  • Pediatricians, surgeons, specialists who assess and treat heart problems (cardiologists), specialists who assess and treat hearing problems (audiologists), specialists who assess and treat eye problems (ophthalmologists), specialists who assess and treat[rarediseases.org]
Hirsutism
  • [rarediseases.org] Skin Hirsutism Patients with MPS III are mentally retarded with severe hirsutism and synophrys. All mucopolysaccharidoses are inherited as autosomal recessive except for the Hunter syndrome (MPS II) which is an x linked disease.[symptoma.com]
  • Patients with MPS III are mentally retarded with severe hirsutism and synophrys. All mucopolysaccharidoses are inherited as autosomal recessive except for the Hunter syndrome (MPS II) which is an x linked disease. CASE REPORT Mrs.[bhj.org.in]
  • Examination of the skin frequently reveals hirsutism. Causes MPS VI results from the deficiency of N- acetylgalactosamine 4-sulfatase (arylsulfatase B) and the lysosomal accumulation of dermatan sulfate.[emedicine.medscape.com]
  • Examples include low and flat nasal bridge, frontal bossing, gingival hypertrophy, macroglossia, and hirsutism. Eyes and ears Patients may have corneal opacification which causes glaucoma and papilledema.[symptoma.com]
  • Abnormal growth of hair on the face or the body may also occur (hirsutism). Some individuals have a short, stiff neck. Clouding (opacity) of the thin transparent covering of the front of the eye (cornea) may also occur.[rarediseases.org]
Corneal Opacity
  • A large head, short neck, corneal opacity, open mouth associated with an enlarged tongue, enlargement of skull, and a long antero-posterior dimension are the main characteristic features.[unboundmedicine.com]
  • [rarediseases.org] Eyes Corneal Opacity A large head, short neck, corneal opacity , open mouth associated with an enlarged tongue, enlargement of skull, and a long antero-posterior dimension are the main characteristic features.[symptoma.com]
  • Corneal opacities can be detected with slitlamp examination. Restricted joint movement, including claw-hand deformities, appears in the first few years of life. Examination of the skin frequently reveals hirsutism.[emedicine.medscape.com]
  • Corneal opacities were found in 3 patients [‎16.7%]‎ and progressive increase in intraocular pressure in 1 patient [‎5.6%]‎, while fundus examination showed early optic atrophy in 1 patient [‎5.6%]‎ and bilateral papilloedema in 2 patients [‎11.1%]‎ Citation[apps.who.int]
  • Corneal opacity was observed in 7/19 cases (36%), and cardiac involvement was observed in 9/19 patients (47%). Mental retardation was present in 8/19 cases (42%).[scielo.br]
Skeletal Dysplasia
  • Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias.[scholars.northwestern.edu]
  • The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease.[orpha.net]
  • [emedicine.medscape.com] Musculoskeletal Skeletal Dysplasia Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias .[symptoma.com]
  • The major clinical manifestations are corneal clouding, joint stiffness, and a skeletal dysplasia known as dysostosis multiplex. Unlike most lysosomal storage disorders, intelligence is unaffected.[egl-eurofins.com]
  • Dysplasia Society, Southeastern Regional Genetics Group Disclosure: Nothing to disclose.[emedicine.medscape.com]
Macrocephaly
  • [symptoma.com] Macrocephaly Macrocephaly and sternal abnormalities can be present at birth, and inguinal/umbilical hernias are common.[symptoma.com]
  • Macrocephaly and sternal abnormalities can be present at birth, and inguinal/umbilical hernias are common. Restriction of joint movement develops sometime in the first few years of life, and a typical crouched posture is assumed.[egl-eurofins.com]
  • The features of MPS VI include macrocephaly, hydrocephalus and macroglossia. Often these individuals also develop abnormalities of heart valves, hepatosplenomegaly and umbilical hernia or inguinal hernia.[ivami.com]
  • Macrocephaly Enlarged tongue Prominent forehead Possible coarse texture of hair Hepatomegaly and splenomegaly are often present in patients with MPS VI. Umbilical and inguinal hernias are common.[emedicine.medscape.com]
  • The phenotype varies significantly from mild to severe presentations and may include macrocephaly, short stature, dysostosis multiplex, hepatomegaly, coarse facies, and impairment of cognitive function.[neurology.testcatalog.org]
Genu Valgum
  • , genu valgum , usually hepatosplenomegaly [medical-dictionary.thefreedictionary.com] Major skeletal abnormalities include hypoplastic bones, hip dysplasia, pectus carinatum, genu valgum , and kyphoscoliosis.[symptoma.com]
  • Ma·ro·teaux-·La·my syn·drome ( mah-rō-tō' lah'mē ), [MIM*253200] an error of mucopolysaccharide metabolism characterized by excretion of dermatan sulfate in the urine, growth retardation, lumbar kyphosis, sternal protrusion, genu valgum, usually hepatosplenomegaly[medical-dictionary.thefreedictionary.com]
  • Major skeletal abnormalities include hypoplastic bones, hip dysplasia, pectus carinatum, genu valgum, and kyphoscoliosis. Major sequelae include spinal cord compression, degenerative joint disease, contractures, and arthritis.[symptoma.com]
  • Additional skeletal malformations may include a prominent breastbone (pectus carinatum), abnormal curvature of the spine, and knock-knees (genu valgum). Skeletal malformations can be associated with a variety of complications.[rarediseases.org]
  • valgum, hypermobile joints Waddling gait with frequent falls Qualitative urine glycosaminoglycan (GAG) analysis demonstrates keratan sulfate and chondroitin 6-sulfate.[centogene.com]
Arthritis
  • [ghr.nlm.nih.gov] Arthritis Major sequelae include spinal cord compression, degenerative joint disease, contractures, and arthritis . The affected individuals often suffer from pain, gait difficulties, and restriction of joint movement.[symptoma.com]
  • Major sequelae include spinal cord compression, degenerative joint disease, contractures, and arthritis. The affected individuals often suffer from pain, gait difficulties, and restriction of joint movement.[symptoma.com]
  • […] case – includes the following diseases: Mucopolysaccharidosis I: Lysosomal storage disease (MPS II, MPS IVA, multiple sulfatase deficiency, mucolipidosis I, mucolipidosis II, mucolipidosis III alpha/beta, and alpha-mannosidosis) Juvenile idiopathic arthritis[centogene.com]
  • Attenuated type I mucopolysaccharidosis in the differential diagnosis of juvenile idiopathic arthritis: a series of 13 patients with Scheie syndrome. Clin Exp Rheumatol. 2006 Mar-Apr. 24(2):196-202. [Medline]. Anawis MA.[emedicine.medscape.com]
  • Copious secretions, temporomandibular joint arthritis, difficult or failed intubations, need for emergency tracheotomy, and intraoperative cardiac arrest have been described.[jamanetwork.com]
Joint Deformity
  • Likewise, the disease causes various skeletal abnormalities which are most noticeable with age, including short stature, joint deformities that affect mobility, dysostosis multiplex, carpal tunnel syndrome and spinal stenosis in the neck that can compress[ivami.com]
  • [rarediseases.org] Joint Deformity Likewise, the disease causes various skeletal abnormalities which are most noticeable with age, including short stature, joint deformities that affect mobility, dysostosis multiplex, carpal tunnel syndrome and spinal[symptoma.com]
  • MPS VI causes various skeletal abnormalities, including short stature and joint deformities (contractures) that affect mobility.[ghr.nlm.nih.gov]
  • deformity with a restricted range of motion, airway dysfunction with complications, sleep apnea, recurrent otitis media, and premature death [ 1, 2, 3, 4 ].[ojrd.biomedcentral.com]
Frontal Bossing
  • [symptoma.com] Face, Head & Neck Frontal Bossing Examples include low and flat nasal bridge, frontal bossing , gingival hypertrophy, macroglossia, and hirsutism.[symptoma.com]
  • Examples include low and flat nasal bridge, frontal bossing, gingival hypertrophy, macroglossia, and hirsutism. Eyes and ears Patients may have corneal opacification which causes glaucoma and papilledema.[symptoma.com]
  • Such characteristics include chubby faces, thickened lips due to the overgrowth of the gums (gingival hypertrophy), an unusually prominent forehead (frontal bossing), and a broad, flattened bridge of the nose.[rarediseases.org]
  • Radiology of skull, face, chest, long bones, and spine showed short stubby small bones, frontal bossing, thick ribs, thickened metaphyses of long bones, spinal thoracolumbar kyphosis highly suggestive of MPS (type IV).[jcor.in]
Papilledema
  • Clinical confirmation of papilledema and communicating hydrocephalus has been obtained in a child with the Maroteaux-Lamy syndrome (mucopolysaccharidosis, Type VI).[jhu.pure.elsevier.com]
  • [rarediseases.org] Neurologic Papilledema Clinical confirmation of papilledema and communicating hydrocephalus has been obtained in a child with the Maroteaux-Lamy syndrome (mucopolysaccharidosis, Type VI).[symptoma.com]
  • Eyes and ears Patients may have corneal opacification which causes glaucoma and papilledema. Hearing loss is common and can occur due to conductive or sensorineural etiologies.[symptoma.com]
  • Some affected individuals may develop hydrocephalus, a condition in which the accumulation of excess cerebrospinal fluid in the skull causes increased pressure on the brain, potentially causing a variety of symptoms, including papilledema.[rarediseases.org]
  • Reversed papilledema in an MPS VI patient with galsulfase (Naglazyme ) therapy. Int Ophthalmol. 2008; 29(4): 267-269. 15. Harmatz P. Enzyme replacement therapy with galsulfase for mucopolysaccharidosis VI: clinical facts and figures. Turk J.[revistamedicina.net]

Workup

Patients suspected to have this disease should be assessed thoroughly through a full personal and family history, a complete physical exam, and the appropriate key tests.

Laboratory testing

The initial diagnostic study is the qualitative and quantitative analysis of urinary GAGs, which establishes the general diagnosis of MPS6. While quantitative assessment yields the measurement of the amount of GAGs, qualitative methods identify the specific GAG that is increased. To obtain the latter, techniques such as thin-layer chromatography (TLC) and/or electrophoresis (ELP) are utilized [11]. It is important that both qualitative and quantitative methods should be performed to avoid false conclusions.

Further studies include the evaluation of the enzymatic activity of ASB using dried blood spots, cultured fibroblasts or leukocytes, of which last two are the gold standard samples [11]. With regards to the level of enzymatic activity, it is not predictive of the clinical course.

If possible the ARSB gene can be assessed for detection of the mutation(s) [11].

Other

Imaging tools should be performed to identify skeletal defects. Furthermore, echocardiography is used to evaluate valvular abnormalities, wall thickness, and other findings. Also, magnetic resonance imaging (MRI) of the brain and spine is important to determine the presence of spinal cord compression, hydrocephalus, and other findings.

Further testing depends on the clinical picture. Hence, additional tests include:

  • Audiogram
  • Ophthalmology assessment
  • Pulmonary function tests

Treatment

Management of patients with MPS6 is best provided by a team of pediatricians, orthopedic surgeons, cardiologists, pulmonologists, dentists, ophthalmologists, audiologists, geneticists, and other specialists as needed.

The two standard treatments currently used are enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT).

ERT

One orphan drug, galsulfase, has been approved by the Food and Drug Association (FDA) since 2005. As a recombinant form of arylsulphatase B, galsulfase provides the patient with an exogenous supply of the deficient enzyme. According to a long-term follow-up study, patients receiving weekly infusions demonstrated a significant decline in urinary GAGs [12]. It is also associated with improvement in walking and stair climbing capacity, and in the range of motion of joints as well [13]. Side effects were deemed acceptable [12].

HSCT

The goal of stem cell transplantation is to endogenously supply the enzyme through the production of a new stem cell population. This treatment is associated with high morbidity and mortality as one study reported a one-year survival rate of 67% [14].

Surgical intervention

Orthopedic surgical procedures may be needed for patients with spinal cord compression, atlantoaxial imbalance, hip dysplasia, carpal tunnel syndrome, and other defects. Additionally, neurosurgery is required for ventriculoperitoneal shunt placement in patients with hydrocephalus. Very importantly, cardiac surgery may be indicated in cases with valvular abnormalities.

Other

Physical rehabilitation including physical and occupational therapy should be instituted early. Additionally, psychosocial support should be provided to the children and their parents. There are resources such as support groups and community programs to assist the families.

Prognosis

The prognosis is influenced by numerous factors, which are the age of onset, the rate of progression, and the age at which therapy was initiated. Additionally, the quality of care received by the patient plays a role in the overall outcome. With regards to biochemical manifestations, a urinary GAG level greater than 100 μg/mg creatinine is indicative of a poor prognosis.

Early recognition and treatment is very important in improving the prognosis since both forms, rapid and slowly progressive, can cause irreversible damage. Therefore, treatment should not be delayed.

In a long-term study, ERT prolonged survival. It was also observed to improve growth, endurance, and pulmonary function [8]. However, ERT did not impact variables measuring the quality of life such as pain or disability [8].

Etiology

The etiology of this autosomal recessive disorder is a mutation in the ARSB gene, which codes for the lysosomal enzyme known as ASB. The latter plays a key role in the breakdown of GAGs such as dermatan sulfate and chondroitin sulfate. Hence, a deficiency in this lysosomal enzyme leads to an accumulation of dermatan sulfate in the various organs and tissues of the body.

Epidemiology

The estimated incidence of MPS6 ranges from 1 in 248,000 to 1 in 300,000 live births [3]. With regards to patient demographics, there is no gender preference.

One community observed to have a higher frequency is the city of Monte Santo located in the northeastern region of Brazil. The prevalence in this population is greater than that noted in the literature [4]. Furthermore, there were numerous patients diagnosed with Maroteaux Lamy syndrome in Colombia [5].

Sex distribution
Age distribution

Pathophysiology

MPS6 develops secondary to mutations on chromosome 5 [5], of which missense mutations account for most of the genetic defects [6].

The disease manifests when there is a profound deficiency in enzymatic activity [7], in which the absent or severely low levels of ASB enzyme are incapable of performing a complete degradation of GAGs. The latter are major components of connective tissues and are constituted of unbranched chains of polysaccharides composed of repetitive disaccharides.

As a result, dermatan sulfate, a type of GAG, builds up in sites that are prominently composed of connective tissue such as the skeleton, joints, heart valves, vessels, ears, eyes, and/or teeth. This disease is characterized by progressive damage to these sites.

There is often multisystem involvement of the skeletal, cardiovascular, respiratory, gastrointestinal, and central nervous systems. Hence, the clinical picture may include bone dysplasia, short stature, joint stiffness, coarse facies, organomegaly, corneal clouding, cardiac and pulmonary abnormalities, etc. Patients commonly have a decreased life expectancy and exhibit decreased exercise capacity, reduced endurance, and a restricted range of motion in the joints [3].

Prevention

While there are no preventative measures, parents with known personal and/or family genetic defects can be offered biochemical prenatal testing. Samples can be obtained from amniocytes [15].

Additionally, patients and family members should seek genetic counseling to receive education about what the disease entails, its mode of inheritance, the prognosis, and other relevant information.

Summary

Mucopolysaccharidosis (MPS) type 6 is also referred to as Maroteaux Lamy syndrome. The MPSs encompass a group of inherited lysosomal disorders that result from mutations in arylsulfatase B (ARSB) gene. The genetic defects lead to a deficiency in the activity of the lysosomal enzyme, ASB, which is necessary for the catabolism of mucopolysaccharides or glycosaminoglycans (GAGs). This culminates in the buildup of GAGS in various organs and tissues.

The clinical manifestations reflect the accumulation of GAGs in the involved connective tissues such as the skeleton, heart valves, eyes, ears, etc. The symptomology varies and includes skeletal dysplasia, dwarfism, joint restriction, abnormal facies, and other features as well [1] [2]. There are two variants which are characterized by the rate of disease progression and age of onset: rapidly progressive and slowly progressive.

The clinical assessment includes the personal and family history, a full physical examination, and appropriate testing. The diagnostic tools consist of the quantitative and qualitative analysis of urinary GAGs followed by the measurement of the enzyme's activity. Additional studies such as a skeletal survey and echocardiogram should be performed in accordance with the clinical picture.

The patients should receive comprehensive care by a multidisciplinary team of specialists. The medical management of Maroteaux Lamy syndrome consists of enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT). ERT is associated with significant improvement in multiple aspects of the disease including survival.

Prompt diagnosis and early treatment with ERT can profoundly impact the outcome. Sometimes Maroteaux Lamy syndrome can be detected prenatally. Genetic counseling is available to affected individuals and their family members.

Patient Information

What is mucopolysaccharidosis (MPS) type 6?

The mucopolysaccharidoses (MPS) is a group of inherited diseases that develop due to a deficiency of a specific type of lysosomal enzyme called arylsulfatase B. Normally, this enzyme breaks down complex carbohydrates called mucopolysaccharides. Therefore, if this enzyme is absent, mucopolysaccharides will accumulate in various organs and tissues such as the skeleton, joints, ears, eyes, skin, heart, liver, and/or teeth.

What causes this disease?

This disease develops as a result of mutations in the ARSB gene, which provides instructions to produce the arylsulfatase B enzyme. Mucopolysaccharidosis type 6 is inherited in an autosomal recessive pattern. In other words, the affected child received two bad copies of the gene, one from each parent.

What are the signs and symptoms?

Some patients will have a rapidly progressive form, in which they develop symptoms between ages 2 and 3 years. Others will have the slowly progressive type which develops at a later onset with a diagnosis often during the second or third decade although they may experience symptoms sooner. Many organs are affected. Signs and symptoms include:

How is it diagnosed?

In children suspected to have mucopolysaccharidosis (MPS) type 6, the clinician will obtain a thorough history of the patient and the family, perform a physical exam, and order the appropriate tests such as:

  • Patient's urine will be assessed for the levels of mucopolysaccharides
  • Blood and skin cells can be evaluated to determine the activity of the enzyme
  • Genetic testing can be done to detect the mutation

Other tests should look for clinical manifestations:

  • X-rays of the skeleton
  • Echocardiography
  • MRI of the brain and spine
  • Audiogram
  • Ophthalmology assessment
  • Pulmonary function tests

How is it treated?

The treatment is best provided by a multidisciplinary team consisting of pediatricians, orthopedic surgeons, cardiologists, pulmonologists, dentists, ophthalmologists, audiologists, geneticists, and other specialists as needed.

The two standard treatments currently used are enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). With ERT, patients are treated with an intravenous medication called Naglazyme (galsulfase), which is a recombinant form of the enzyme. Therefore, the patient receives the missing enzyme through the treatment.

Stem cell transplantation is associated with severe side effects and high risk of death.

What is the prognosis?

It is important to diagnose and treat the disease as soon as possible. Treatment with enzyme replacement therapy has shown to improve survival, walking, endurance, and joint movement.

Can this be prevented?

Since this disease is inherited, it cannot be prevented. Patients and affected family members are encouraged to receive genetic counseling to learn about the disease, what it entails, how it is inherited, and other important information.

The family should be provided with numerous community and state resources.

References

Article

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Last updated: 2019-07-11 20:42