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Mucopolysaccharidosis 2

Hunter's Syndrome

Mucopolysaccharidosis type II (MPS 2), also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase.

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Presentation

Mucopolysaccharidosis 2 presents with a progressive multisystem involvement due to glycosaminoglycan accumulation in virtually all tissues and organs.

Signs and symptoms of MPS 2A include:

The presentation of MPS 2B usually occurs in adolescence or adulthood. Typical signs and symptoms include:

Some of these manifestations are seen in a lesser degree in MPS 2B compared to MPS 2A.

Splenomegaly
  • Individuals with this disorder may experience the following signs: abnormal retina, heart murmur and leaky heart valves, enlarged liver (hepatomegaly) enlarged spleen (splenomegaly), inguinal hernia, and joint contractures.[secure.ssa.gov]
  • […] upper respiratory infections Stunted growth Multiple skeletal deformities; degenerative joints causing joint stiffness Spinal cord defects Sleep disorder such as sleep apnea Decrease in mental cognition Enlarged liver (hepatomegaly) and enlarged spleen (splenomegaly[dovemed.com]
  • […] signs and symptoms include coarse facial features, vision loss [ 29 ], hearing loss [ 30 ], decreased pulmonary function and obstructive sleep apnoea [ 31 ], frequent and recurrent respiratory infections, cardiac disease [ 32 , 33 ], hepatomegaly and splenomegaly[rheumatology.oxfordjournals.org]
  • Gastrointestinal Hepatomegaly and/or splenomegaly occur in most affected individuals. Umbilical/inguinal hernia is also a frequent finding. In persons with early progressive MPS II, chronic diarrhea is a common complaint.[ncbi.nlm.nih.gov]
Hoarseness
  • Common signs and symptoms include a large head, full lips, large rounded cheeks, a broad nose, hoarse voice and an enlarged tongue (macroglossia). Upper respiratory infections and sleep apnea are frequent.[symptoma.com]
  • Signs and symptoms may include: An enlarged head (macrocephaly) Thickening of the lips A broad nose and flared nostrils A protruding tongue A deep, hoarse voice Abnormal bone size or shape and other skeletal irregularities A distended abdomen, as a result[mayoclinic.org]
  • Symptoms include: Facial changes such as thickening of the lips, nostrils flaring and broadening of the nose Head enlargement (macrocephaly) Tongue protrusion Hoarseness and/or deepening of the voice Changes in the bones produces abnormal bone size and[medicinenet.com]
  • The vocal cords also enlarge, which results in a deep, hoarse voice. Narrowing of the airway causes frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea).[ghr.nlm.nih.gov]
  • Early signs of MPS II: Distinctively large facial features (full lips, large rounded cheeks, broad nose, enlarged tongue) Enlargement of vocal cords causing deep, hoarse voice Frequent upper respiratory infections Short pauses in breathing during sleep[babysfirsttest.org]
Clubbed Finger
  • On examination, he was short statured, with a big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers. There was mild mental retardation.[amhsr.org]
  • On examination, they had short stature, big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers.[mjdrdypu.org]
Hepatosplenomegaly
  • Initial manifestations include: frequent respiratory tract infections (in particular otitis media); umbilical and inguinal hernia; intractable diarrhea; hepatosplenomegaly; and skin lesions resembling an orange peel (on the shoulder, back and thighs).[orpha.net]
  • Hepatosplenomegaly, hearing loss, hernias, and carpal tunnel syndrome are often present.[disorders.eyes.arizona.edu]
  • Mucopolysaccharidosis Type VI also known as Maroteaux-Lamy syndrome is an error of mucopolysaccharide metabolism characterized by excretion of dermatan sulfate in the urine, growth retardation, lumbar kyphosis, sternal protrusion, genu valgum, usually hepatosplenomegaly[drugs.com]
  • Phenotypically, persons with MPS IIA have a short neck, broad chest, a protuberant abdomen, hepatosplenomegaly, and an umbilical hernia.[emedicine.medscape.com]
Hepatomegaly
  • Level II ultrasound showed cardiomegaly and hepatomegaly. The pregnancy was terminated at 22 weeks' gestation.[questia.com]
  • Ivory-colored papular skin lesions on the upper back and sides of the upper arms Protuberant abdomen Diarrhea Short stature Skeletal deformities Joint stiffness Inguinal or umbilical hernia Developmental delay Intellectual disability Hyperactivity Seizures Hepatomegaly[symptoma.com]
  • Individuals with this disorder may experience the following signs: abnormal retina, heart murmur and leaky heart valves, enlarged liver (hepatomegaly) enlarged spleen (splenomegaly), inguinal hernia, and joint contractures.[secure.ssa.gov]
  • This is akin to what happens in glycogen storage disease where degeneration of excess glycogen in the liver can cause tender hepatomegaly.[ 8 ] It has a prevalence of 1 in 170,000 males live births.[ 5 ] In Nigeria, however, there is no known study to[amhsr.org]
  • The ultrasonography of abdomen and kidney revealed hepatomegaly. The audiological test was normal. The Echocardiography showed left to right shunt at ventricular level with 9 mm VSD.[omicsonline.org]
Abnormal Behavior
  • Abnormal behavior can develop in children with more-severe cases of Hunter syndrome. Often your child's mental development will become affected between the ages of 2 and 6.[mayoclinic.org]
Seizure
  • Box parents of children Park School physical disabilities Profound & Multiple publications pupils Residential Special Needs RNIB Road School:Day Special Needs Seealso seizures Severe Learning Difficulties skull Special Educational Needs Special School[books.google.com]
  • […] chest Ivory-colored papular skin lesions on the upper back and sides of the upper arms Protuberant abdomen Diarrhea Short stature Skeletal deformities Joint stiffness Inguinal or umbilical hernia Developmental delay Intellectual disability Hyperactivity Seizures[symptoma.com]
  • Keywords: Hunter syndrome, mucopolysaccharidosis II, lysosomal storage disorder, developmental delay, cognitive impairment, neurology, neurological symptoms, seizures, spinal cord compression, neuronopathic[touchneurology.com]
  • Seizures also may occur in children with Hunter syndrome. Longer recovery from other illnesses Recovery times from normal childhood illnesses may be longer for children with Hunter syndrome.[mayoclinic.org]
  • There was no history of constipation, diarrhea, vomiting, bleeding, jaundice , seizure, weight loss or loss of appetite or of consciousness. His bladder habit was normal. The scholastic performance was poor.[omicsonline.org]
Hyperactivity
  • The symptoms include: aggressive behavior, hyperactivity, mental function decline, severe intellectual disability and spasticity.[secure.ssa.gov]
  • […] media Broad chest Ivory-colored papular skin lesions on the upper back and sides of the upper arms Protuberant abdomen Diarrhea Short stature Skeletal deformities Joint stiffness Inguinal or umbilical hernia Developmental delay Intellectual disability Hyperactivity[symptoma.com]
  • Some children are hyperactive and have trouble paying attention or following directions. Your child may also behave aggressively and seem unable to sense danger.[mayoclinic.org]
  • Additional features at presentation or upon reevaluation may include hyperactivity, retinal degeneration, progressive hearing loss, recurrent ear infections, hepatomegaly, and carpal tunnel syndrome.[emedicine.medscape.com]
  • Behavioral disturbances can often mimic combinations of symptoms of attention deficit hyperactivity disorder , autism , obsessive compulsive disorder , and/or sensory processing disorder , although the existence and level of symptoms differ in each affected[en.wikipedia.org]
Communicating Hydrocephalus
  • Communicating hydrocephalus can also be present and further contribute to neurological deterioration. Carrier-testing for individuals and families at risk is available.[symptoma.com]
  • Communicating hydrocephalus does not occur as often, although papilledema has been seen in the absence of increased intracranial pressure, suggesting a localized process involving the optic nerves.[emedicine.medscape.com]
  • Mps iia usually occurs between 2 and 4 years of age with progressive deterioration, chronic diarrhea, recurrent ear infections, hearing impairment, communicating hydrocephalus with increased intracranial pressure, and death at about 10 and 15 years.[icd10data.com]
  • Communicating hydrocephalus is a common finding in Hunter's syndrome and can lead to severe manifestation of neurological signs, which however, were not present in our cases.[mjdrdypu.org]
  • Neurological involvement, such as cervical spine instability and communicating hydrocephalus, is common in MPS IV and can be life threatening.[rheumatology.oxfordjournals.org]
Stroke
  • National Institute of Neurological Disorders and Stroke . 15 Nov 2017 . Retrieved 11 May 2018 . a b c d e f g Wraith JE, Scarpa M, Beck M, et al. (March 2008).[en.wikipedia.org]
  • Central nervous system complications may include transient ischaemic attacks and early stroke.[touchophthalmology.com]
  • The National Institute of Neurological Disorders and Stroke. National Institutes of Health . Online Mendelian Inheritance in Man (OMIM). National Center for Biotechnology Information. Sharon A.[encyclopedia.com]
  • The National Institute of Neurological Disorders and Stroke. National Institutes of Health. . Online Mendelian Inheritance in Man (OMIM).[medical-dictionary.thefreedictionary.com]
Psychomotor Regression
  • Progression varies from a severe form (MPS2, severe form) with early psychomotor regression to an attenuated form (MPS2, attenuated form) which manifests without cognitive involvement.[orpha.net]
  • Central nervous system involvement depends on the form and may include learning difficulties and psychomotor regression. Communicating hydrocephalus can also be present and further contribute to neurological deterioration.[symptoma.com]
Short Stature
  • Early bone involvement leads to decreased growth velocity and short stature in nearly all patients.[ncbi.nlm.nih.gov]
  • Mucopolysaccharidosis type II is a multisystem disorder and symptoms include coarse face, short stature, skeletal abnormalities, recurrent infections, cardiomyopathy, hepatomegaly, umbilical and inguinal hernia, diarrhea, developmental delay, and intellectual[symptoma.com]
  • Short stature is usually not noted until after age 3 years.[emedicine.medscape.com]
  • Physical Findings: Coarse facial features, thickened skin, narrowing of the cervical spinal canal (spinal stenosis), short stature, enlarged tongue (macroglossia) and vocal cords, enlarged liver and spleen, retinal degeneration, contractures of the joints[secure.ssa.gov]
  • Joint stiffness, short stature, and skeletal deformities are common. Many have short necks, a protuberant abdomen, a broad chest, and facial coarseness. Hepatosplenomegaly, hearing loss, hernias, and carpal tunnel syndrome are often present.[disorders.eyes.arizona.edu]
Inguinal Hernia
  • Individuals with this disorder may experience the following signs: abnormal retina, heart murmur and leaky heart valves, enlarged liver (hepatomegaly) enlarged spleen (splenomegaly), inguinal hernia, and joint contractures.[secure.ssa.gov]
  • Initial manifestations include: frequent respiratory tract infections (in particular otitis media); umbilical and inguinal hernia; intractable diarrhea; hepatosplenomegaly; and skin lesions resembling an orange peel (on the shoulder, back and thighs).[orpha.net]
  • Mucopolysaccharidosis type II is a multisystem disorder and symptoms include coarse face, short stature, skeletal abnormalities, recurrent infections, cardiomyopathy, hepatomegaly, umbilical and inguinal hernia, diarrhea, developmental delay, and intellectual[symptoma.com]
  • Child with unusual appearance, inguinal hernia, accelerated growth, and developmental delay. Consultant Pediatricians. 2007;6(3):149-152. 2. Al-Jasmi F, Clarke JTR, Moldovan L. Lysosomal storage diseases. . 2008. Accessed February 3, 2015. 3.[consultant360.com]
  • Anesthetic/Surgical concerns Two patients are in need of surgical repair for inguinal hernia, three for umbilical hernia and one for gastrostomy insertion.[actamedicaphilippina.com.ph]
Coarse Facial Features
  • Other symptoms may include: carpal tunnel syndrome, coarse facial features, deafness, hairy body (hypertrichosis), joint stiffness and a large head (macrocephaly).[secure.ssa.gov]
  • There are some obvious physical signs of Hunter syndrome, such as coarse facial features and an enlarged liver and spleen, as well as some less noticeable symptoms. 2 Symptoms range from patient to patient but here are the key signs: 3 Hunter syndrome[rare2aware.com]
  • Figure 1: shows Coarse facial features with depressed nasal bridge, a short neck, long philtrum. Figure 2: showing dorso lumbar scoliosis with anterior breaking at D12, L1,2,3 with ovoid shaped vertebra.[omicsonline.org]
  • Forty percent (40%) of the patients presented with coarse facial features.[actamedicaphilippina.com.ph]
  • Keywords Prenatal Diagnosis Carpal Tunnel Syndrome Hunter Syndrome Mucopolysaccharidosis Type Coarse Facial Feature These keywords were added by machine and not by the authors.[link.springer.com]
Developmental Delay
  • Mucopolysaccharidosis type II is a multisystem disorder and symptoms include coarse face, short stature, skeletal abnormalities, recurrent infections, cardiomyopathy, hepatomegaly, umbilical and inguinal hernia, diarrhea, developmental delay, and intellectual[symptoma.com]
  • Keywords: Hunter syndrome, mucopolysaccharidosis II, lysosomal storage disorder, developmental delay, cognitive impairment, neurology, neurological symptoms, seizures, spinal cord compression, neuronopathic[touchneurology.com]
  • SUGGESTED PROGRAMMATIC ASSESSMENT* Suggested MER for Evaluation: Enzyme assay for iduronate sulfatase; evidence of progressive neuro-developmental delay; physical examination of the eyes, heart, liver, spleen, respiratory, neurologic and musculoskeletal[secure.ssa.gov]
  • Systemic Features: Mild to severe developmental delays are common and mental retardation has been reported in some cases. There is often 'pebbling' of the skin over the neck and chest.[disorders.eyes.arizona.edu]
  • delays (physical and mental) The cause of Hunter syndrome is due to a defective X chromosome that males usually inherit from the mother.[medicinenet.com]
Dysostosis
  • Extensive palliative care is required, patients must be regularly evaluated by echocardiogram, respiratory function, full radiologic examination to identify dysostosis multiplex, cranial and cervical MRI with or without lumbar puncture to assess cerebrospinal[orpha.net]
  • X-rays - show features of dysostosis multiplex which are due to disordered ossification at varied sites. Audiometry. Brain CT/MRI - characteristic cerebral changes. Spirometry to look for airflow obstruction.[patient.info]
  • Sixteen years later, physicians Binswanger and Ullrich coined the term dysostosis multiplex to describe the constellation of skeletal findings specific to persons with MPS and other lysosomal storage disorders.[emedicine.medscape.com]
  • The group of abnormalities typically seen in the bones of people with Hunter syndrome is called dysostosis multiplex.[mayoclinic.org]
  • The typical coarse features are most likely caused by a combination of storage in the soft tissues of the orofacial region and underlying facial bone dysostosis.[actamedicaphilippina.com.ph]
Diarrhea
  • Skeletal irregularities, vision problems, heart problems, diarrhea, joint stiffness, stunted growth and delayed development may be present.[symptoma.com]
  • Initial manifestations include: frequent respiratory tract infections (in particular otitis media); umbilical and inguinal hernia; intractable diarrhea; hepatosplenomegaly; and skin lesions resembling an orange peel (on the shoulder, back and thighs).[orpha.net]
  • […] of Hunter syndrome range from mild to severe and may include the following: Facial changes Head enlargement Abnormal bone size and shapes Tongue protrusion Voice changes Joint stiffness Small growths on skin Distended abdomen Enlarged internal organs Diarrhea[medicinenet.com]
  • Mps iia usually occurs between 2 and 4 years of age with progressive deterioration, chronic diarrhea, recurrent ear infections, hearing impairment, communicating hydrocephalus with increased intracranial pressure, and death at about 10 and 15 years.[icd10data.com]
  • […] enlarged head (macrocephaly) Thickening of the lips A broad nose and flared nostrils A protruding tongue A deep, hoarse voice Abnormal bone size or shape and other skeletal irregularities A distended abdomen, as a result of enlarged internal organs Diarrhea[mayoclinic.org]
Macroglossia
  • Oropharyngeal and tracheobronchial deposition of glycosaminoglycans results in airway obstruction due to macroglossia, supraglottic narrowing, and tracheomalacia.[symptoma.com]
  • Physical Findings: Coarse facial features, thickened skin, narrowing of the cervical spinal canal (spinal stenosis), short stature, enlarged tongue (macroglossia) and vocal cords, enlarged liver and spleen, retinal degeneration, contractures of the joints[secure.ssa.gov]
  • Manifestations of MPS II may include joint stiffness, with associated restriction of movements; and coarsening of facial features, including thickening of the lips, tongue (macroglossia), and nostrils.[rarediseases.org]
  • Between ages 2 and 4, they develop full lips, large rounded cheeks , a broad nose , and an enlarged tongue ( macroglossia ). The vocal cords also enlarge, which results in a deep, hoarse voice.[ghr.nlm.nih.gov]
  • The commonly observed signs and symptoms of Mucopolysaccharidosis may include: Thick, coarse facial features; enlarged skull Presence of large tongue (macroglossia) Abnormal development of vocal cords; individuals have deep, hoarse voice Abnormal bone[dovemed.com]
Widely Spaced Teeth
  • Thick skin, short neck, widely spaced teeth, and hearing loss of varying degree are also commonly present. Nodular skin lesions on the arm or the posterior chest wall, extra- high arched feet (pes cavus) and diarrhea may also occur.[rarediseases.org]
  • Inspection of the oropharynx can reveal widely spaced teeth and an enlarged tongue. The enlarged tongue is more pronounced in children older than 5 years.[emedicine.medscape.com]
  • spaced teeth, coarse facies, skin thickening, claw and shortened fingers (bradydactyly) with painless nodules.[amhsr.org]
Skin Thickening
  • thickening, claw and shortened fingers (bradydactyly) with painless nodules.[amhsr.org]
Retinal Pigmentation
  • Abnormal retinal pigmentation and papilloedema - leading to visual impairment. Type B - mild form This usually presents later and may not be noticed until adulthood.[patient.info]
  • Del Monte MA, Maumenee IH, Edwards RB, Glycosaminoglycan degradation by cultured retinal pigment epithelium from patients with retinitis pigmentosa, Curr Eye Res, 1991;10:241–8.[touchophthalmology.com]
  • However, signs and symptoms do not necessarily correlate with ERG change, as often only minimal changes are observed in the retinal pigment epithelium despite significant ERG changes [ Ashworth et al 2006 ].[ncbi.nlm.nih.gov]
Hearing Impairment
  • The symptoms usually include hearing impairment, carpal tunnel syndrome, joint stiffness, discrete corneal opacities, and papilledema. Death may occur in early adulthood, usually from airway obstruction or cardiac failure.[icd10data.com]
  • Typical signs and symptoms include: Hearing impairment Joint stiffness Coarse face Upper airway disease Carpal tunnel syndrome Communicating hydrocephalus Retinal degeneration Some of these manifestations are seen in a lesser degree in MPS 2B compared[symptoma.com]
  • Hearing impairment, joint stiffness, coarse facial features, upper airway disease, and carpal tunnel syndrome as seen in MPS IIA remain hallmarks in MPS IIB, but become evident over a more protracted time period.[emedicine.medscape.com]
  • Recurrent upper respiratory infections, a chronic runny nose, hearing impairment, liver and spleen enlargement, inguinal and abdominal hernias, joint stiffness and multiplex dysplasia, compression of tendines in the wrist (carpal tunnel syndrome), and[rarediseases.org]
  • Recurrent otitis media is a frequent problem and may lead to conductive hearing impairment. Otosclerotic deformation of auditory ossicles as well as cytoplasmic inclusions in the spiral ganglion has also been reported.[actamedicaphilippina.com.ph]
Hearing Problem
  • Hearing problems. Swollen and stiff joints. Abdominal hernias. Hepatosplenomegaly.[patient.info]
  • He may be eligible for one-on-one attention in the classroom or help for other issues, like hearing problems. Take care of yourself, too .[webmd.com]
  • The most usual clinical manifestations are short stature, coarse facial features, mental retardation, respiratory and cardiovascular complications, bowel dysfunction, organomegaly, umbilical or inguinal hernias, hearing problems, ocular impairment, and[karger.com]
  • Hearing problems are common in the MPS disorders. Regular hearing evaluations are important so that children with hearing loss can be treated early. Hearing aids may provide some degree of improvement.[encyclopedia.com]
Joint Stiffness
  • Skeletal irregularities, vision problems, heart problems, diarrhea, joint stiffness, stunted growth and delayed development may be present.[symptoma.com]
  • Common presenting features include excess urinary glycosaminoglycan excretion, facial dysmorphism, organomegaly, joint stiffness and contractures, pulmonary dysfunction, myocardial enlargement and valvular dysfunction, and neurologic involvement.[pediatrics.aappublications.org]
  • MPS IIA Common presenting signs and symptoms in children with classic MPS IIA include progressive coarsening of facial features, short stature, joint stiffness, hepatosplenomegaly, and hernias.[emedicine.medscape.com]
  • Joint stiffness is caused by swelling of joint connective tissues and abnormalities of cartilage and bones. If your child is in pain, he or she will likely move less, which can lead to more stiffness and pain.[mayoclinic.org]
Macrocephaly
  • Other symptoms may include: carpal tunnel syndrome, coarse facial features, deafness, hairy body (hypertrichosis), joint stiffness and a large head (macrocephaly).[secure.ssa.gov]
  • Macrocephaly develops during infancy and infants initially grow at normal or above average rates.[orpha.net]
  • Signs and symptoms of MPS 2A include: Macrocephaly Coarse facies Large rounded cheeks Thick lips Hypertrophic adenoids and tonsils Macroglossia Hoarse voice Short neck Retinal degeneration Hearing loss Recurrent otitis media Broad chest Ivory-colored[symptoma.com]
  • The skin may also show hypertrichosis and excessive Mongolian spots. [ 6 ] Other features Macrocephaly - common with a short trunk length compared to the extremities. Short stature - develops gradually after the age of 3.[patient.info]
  • Signs and symptoms may include: An enlarged head (macrocephaly) Thickening of the lips A broad nose and flared nostrils A protruding tongue A deep, hoarse voice Abnormal bone size or shape and other skeletal irregularities A distended abdomen, as a result[mayoclinic.org]
Skeletal Dysplasia
  • Manifestations of abnormal cell function include syndromic intellectual disability, growth failure , and skeletal dysplasia . GAGs accumulate in lysosomes and extracellular tissue and are excreted in the urine.[emedicine.medscape.com]
  • Dysplasia Society , Southeastern Regional Genetics Group Disclosure: Nothing to disclose.[emedicine.medscape.com]
  • The characteristic skeletal dysplasia includes short stature, dysostosis multiplex, and degenerative joint disease. Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births 33 .[centogene.com]
  • Of interest to the rheumatologist, the skeletal dysplasia is distinct from the dysostosis multiplex seen in MPS I, II and VII.[rheumatology.oxfordjournals.org]
Swollen Wrist Joints
  • On examination, he was short statured, with a big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers. There was mild mental retardation.[amhsr.org]
  • On examination, they had short stature, big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers.[mjdrdypu.org]
Short Neck
  • Many have short necks, a protuberant abdomen, a broad chest, and facial coarseness. Hepatosplenomegaly, hearing loss, hernias, and carpal tunnel syndrome are often present.[disorders.eyes.arizona.edu]
  • Signs and symptoms of MPS 2A include: Macrocephaly Coarse facies Large rounded cheeks Thick lips Hypertrophic adenoids and tonsils Macroglossia Hoarse voice Short neck Retinal degeneration Hearing loss Recurrent otitis media Broad chest Ivory-colored[symptoma.com]
  • Figure 1: shows Coarse facial features with depressed nasal bridge, a short neck, long philtrum. Figure 2: showing dorso lumbar scoliosis with anterior breaking at D12, L1,2,3 with ovoid shaped vertebra.[omicsonline.org]
  • Thick skin, short neck, widely spaced teeth, and hearing loss of varying degree are also commonly present. Nodular skin lesions on the arm or the posterior chest wall, extra- high arched feet (pes cavus) and diarrhea may also occur.[rarediseases.org]
  • Phenotypically, persons with MPS IIA have a short neck, broad chest, a protuberant abdomen, hepatosplenomegaly, and an umbilical hernia.[emedicine.medscape.com]
Thick Lips
  • Signs and symptoms of MPS 2A include: Macrocephaly Coarse facies Large rounded cheeks Thick lips Hypertrophic adenoids and tonsils Macroglossia Hoarse voice Short neck Retinal degeneration Hearing loss Recurrent otitis media Broad chest Ivory-colored[symptoma.com]
  • Hunter syndrome usually affects how the boy looks: Large, round cheeks Broad nose Thick lips and a large tongue Bushy eyebrows Large head Slowed growth Thick, tough skin Short, broad hands with stiff, curled fingers He'll probably have these symptoms:[webmd.com]
  • Photographs demonstrating coarse facies of patients with Mucopolysaccharidosis Type II (Note the broad nose with flared nostrils, large jowls and thick lips) [Photographs are published with consent].[actamedicaphilippina.com.ph]
  • On examination, the patient was small and nonobese (height 130 cm, weight 40 kg) and had a rough phenotype with macrocephaly, prominent eyes, coarse nose, thick lips and eyebrows, broad hands with fat thumbs, short limbs, and a tendency to semiflexion[karger.com]
  • Coarsening of facial features – the result of macroglossia, prominent supraorbital ridges, a broad nose, a broad nasal bridge, and deposition of GAG in the soft tissues of the face resulting in large rounded cheeks and thick lips – generally manifests[ncbi.nlm.nih.gov]
Frontal Bossing
  • Anteroposterior and lateral X-rays of the skull showed an calvarial thickening and depressed bridge of nose with frontal bossing with hypopneumatised mastoid ( Figure 3 ).[omicsonline.org]
  • Systemic examination showed a distended abdomen, and his liver was 16 cm from xiphisternum which was tender with occipito-frontal circumference of 59 cm (macrocephaly), ridging of the sutures, widened nasal bridge, frontal bossing, capud quadratum, widely[amhsr.org]
Coarse Face
  • Typical signs and symptoms include: Hearing impairment Joint stiffness Coarse face Upper airway disease Carpal tunnel syndrome Communicating hydrocephalus Retinal degeneration Some of these manifestations are seen in a lesser degree in MPS 2B compared[symptoma.com]
  • A male fetus was delivered with a body weight of 586 g, a body length of 29 cm, and a coarse face with prominent supraorbital ridges and a depressed nasal bridge. Postnatal molecular analysis of the fetal tissues confirmed the prenatal diagnosis.[questia.com]
Broad Nasal Bridge
  • Coarsening of facial features – the result of macroglossia, prominent supraorbital ridges, a broad nose, a broad nasal bridge, and deposition of GAG in the soft tissues of the face resulting in large rounded cheeks and thick lips – generally manifests[ncbi.nlm.nih.gov]

Workup

The clinical diagnosis requires a thorough patient medical and family history and an examination of the clinical signs. The detection of increased levels of dermatan sulfate and heparan sulfate in the urine is followed by the definitive biochemical diagnosis of MPS 2 through enzyme testing in leukocytes, fibroblasts or plasma. To establish the extent of the disorder, the following tests are recommended:

Molecular genetic testing is usually not needed to establish a diagnosis.

Microcytosis
  • Blood film: Anisopoikilocytosis, microcytosis, hypochromia with pencil cells (showing iron deficiency). SEUC; urea: 20 mg/dl (2.5–6.4 mg/dl).[amhsr.org]
Anisopoikilocytosis
  • Blood film: Anisopoikilocytosis, microcytosis, hypochromia with pencil cells (showing iron deficiency). SEUC; urea: 20 mg/dl (2.5–6.4 mg/dl).[amhsr.org]
Enlargement of the Spleen
  • There are some obvious physical signs of Hunter syndrome, such as coarse facial features and an enlarged liver and spleen, as well as some less noticeable symptoms. 2 Symptoms range from patient to patient but here are the key signs: 3 Hunter syndrome[rare2aware.com]
  • Individuals with this disorder may experience the following signs: abnormal retina, heart murmur and leaky heart valves, enlarged liver (hepatomegaly) enlarged spleen (splenomegaly), inguinal hernia, and joint contractures.[secure.ssa.gov]
  • Hydrocephalus, an enlarged liver and spleen and hernias occur often. Most patients with MPS 2 have progressive hearing loss and recurrent infections of the middle ear.[symptoma.com]
  • […] liver and spleen Bone thickening When a boy's brain is affected, it's likely he'll have: Trouble thinking and learning by the time he is 2 to 4 years old Trouble talking Behavior problems such as a hard time sitting still or aggression Kids who have[webmd.com]
  • Symptoms of MPS I MPS II Abnormal bones, including shortened stature and spine problems Intellectual disabilities Heart disease Enlarged liver and spleen Joint stiffness Vision or hearing loss Depression Chronic Pain Shortened lifespan Prevalence / Incidence[sangamo.com]

Treatment

At this time, there is no curative treatment of MPS 2. The relevant enzyme can be administered to patients as enzyme replacement therapy and initiation should be done as early as possible [14] [15]. Bone marrow transplantation is another treatment modality [16] [17]. Cranial shunting should be performed in case of hydrocephalus. Hernia repair, carpal tunnel release, tonsillectomy and adenoidectomy, positive pressure ventilation or tracheostomy may be required. Cardiac valve or hip replacement may be necessary over the course of the disease. Developmental, physical, and occupational therapy are often beneficial. A multidisciplinary team approach is important in the management of MPS 2.

Prognosis

Affected individuals appear normal at birth, and age at presentation and progression of the disease vary. In MPS 2A life expectancy is markedly reduced and death frequently occurs in the first or second decade of life, usually due to respiratory or cardiac disease. In the milder form, patients may survive into adulthood, and their intelligence is frequently not affected.

Etiology

The mucopolysaccharidoses are a group of inherited metabolic disorders caused by genetic defects that lead to the the absence or deficiency of one of the lysosomal hydrolases required for the degradation of glycosaminoglycans. Mucopolysaccharidosis type II is caused by a deficiency of iduronate sulfatase, which normally cleaves a sulfate group from the glycosaminoglycans dermatan sulfate and heparan sulfate. The undegraded glycosaminoglycans accumulate within the lysosomes of various organs and tissues, resulting in their dysfunction, producing a wide variety of progressive symptoms [6].

Epidemiology

The incidence of the disorder varies. Schaap and Bach reported an incidence of 1 case per 34,000 males in Israel [7]. Young and Harper estimated the frequency of the disorder in the United Kingdom as about 1 in 132,000 male births [8]. 1 case per 111,000 was found in British Columbia [9]. Studies from Germany and the Netherlands reported an incidence of 1 case per 77,000 male births [10]. The severe form, MPS 2A, appears usually in children aged 2-4 years, while the mild form is frequently diagnosed later. Although this X-linked recessive condition occurs almost exclusively in males, it has also been reported to affect a small group of female individuals.

Sex distribution
Age distribution

Pathophysiology

Mucopolysaccharidosis type II is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate sulfatase. This enzyme cleaves O-linked sulphate moieties from the glycosaminoglycans dermatan sulfate and heparan sulfate in the first step of their degradative pathway. The clinical phenotype of the condition is caused by progressive accumulation of undegraded glycosaminoglycans in nearly all cell types, tissues and organs.

Oropharyngeal and tracheobronchial deposition of glycosaminoglycans results in airway obstruction due to macroglossia, supraglottic narrowing, and tracheomalacia. In the course of the disease, also pulmonary restriction secondary to thoracic skeletal manifestations occurs. Valvular heart leaflets become dysfunctional due to glycosaminoglycan deposition, cardiomyopathy develops and, in conjunction with respiratory disorders, pulmonary hypertension occurs. Bone and joint involvement leads to skeletal deformities and joint stiffness. Central nervous system involvement depends on the form and may include learning difficulties and psychomotor regression. Communicating hydrocephalus can also be present and further contribute to neurological deterioration.

Prevention

Carrier-testing for individuals and families at risk is available.

Summary

Mucopolysaccharidosis type II (MPS 2), also known as Hunter syndrome or Iduronate 2-Sulfatase Deficiency, is an inherited metabolic disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase, characterized by accumulation of glycosaminoglycans (GAG). The location of the causative gene is Xq28 and more than 300 mutations have been reported to cause the disorder. It is an X-linked recessive condition and expected to be found in males, but on rare occasions, affected females have been reported. Two types of MPS 2 exist, the severe form MPS 2A and the milder form MPS 2B [1] [2].

Mucopolysaccharidosis type II is a multisystem disorder and symptoms include coarse face, short stature, skeletal abnormalities, recurrent infections, cardiomyopathy, hepatomegaly, umbilical and inguinal hernia, diarrhea, developmental delay, and intellectual disability [2]. To establish a diagnosis, the detection of increased levels of dermatan sulfate and heparan sulfate in the urine is followed by the definitive biochemical diagnosis of MPS 2 through enzyme testing in leukocytes, fibroblasts or plasma [3] [4] [5]. Molecular genetic testing may also be useful. Enzyme replacement therapy (ERT), bone marrow transplantation and management of the complications are the main treatment options.

Patient Information

Mucopolysaccharidosis type II (MPS 2), also known as Hunter syndrome, I2S deficiency or Iduronate 2-sulfatase deficiency, is a progressive, inherited condition that affects many different organs and occurs almost only in males. At birth, affected individuals do not have any symptoms. They develop either in childhood or adolesense, because there are two types of MPS 2.

Common signs and symptoms include a large head, full lips, large rounded cheeks, a broad nose, hoarse voice and an enlarged tongue (macroglossia). Upper respiratory infections and sleep apnea are frequent. Hydrocephalus, an enlarged liver and spleen and hernias occur often. Most patients with MPS 2 have progressive hearing loss and recurrent infections of the middle ear. Skeletal irregularities, vision problems, heart problems, diarrhea, joint stiffness, stunted growth and delayed development may be present. The more severe type of MPS 2 is characterized by a decline in intellectual function and a more rapid progression.

The diagnosis can be made by examination of urine and blood, a genetic analysis can confirm it. The treatment focuses on managing signs and symptoms and depends also on the organs affected and the form of the disease. Intravenous enzyme replacement therapy (ERT) has been shown to alleviate symptoms.

References

Article

  1. McKusick VA. The Mucopolysaccharidoses. Heritable Disorders of Connective Tissue. St. Louis: C. V. Mosby (pub.) (4th ed.) : 1972. Pp. 556-574.
  2. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Lund AM, Malm G, Van der Ploeg AT, Zeman J. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Europ. J. Pediat. 167: 267-277, 2008.
  3. Martin R, Beck M, Eng C, Giugliani R, Harmatz P, Munoz V and Muenzer J (2008) Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics 121:e377-e386. 
  4. Guelbert N, Amartino H, Arberas C, Azar N, Bay L, Faiboim A, Fernandez MC, Giner A, Ilari R, Marchione D, et al. (2011) Guideline for diagnosis, follow-up and treatment of mucopolysaccharidoses type II or Hunter disease. Arch Argent Pediatr 109:175-181 
  5. Scarpa M, Almassy Z, Beck M, Bodamer O, Bruce IA, De Meirleir L, Guffon N, Guillen-Navarro E, Hensman P, Jones S, et al. (2011) Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis 6:72.
  6. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, Volume III. 8th edition. 2001. McGraw-Hill, New York, pp 3421-3452. 
  7. Schaap T, Bach G. Incidence of mucopolysaccharidoses in Israel: is Hunter disease a 'Jewish disease'? Hum. Genet. 56: 221-223, 1980. 
  8. Young ID, Harper PS. Incidence of Hunter's syndrome. (Letter) Hum. Genet. 60: 391-392, 1982.
  9. Lowry RB, Applegarth DA, Toone JR, MacDonald E, Thunem NY. An update on the frequency of mucopolysaccharide syndromes in British Columbia. Hum. Genet. 85: 389-390, 1990.
  10. Wraith JE, Beck M, Giugliani R, Clarke J, Martin R, Muenzer J. Initial report from the Hunter Outcome Survey. Genet Med. 2008 Jul. 10(7):508-16.
  11. Tylki-Szymańska A. Mucopolysaccharidosis type II, Hunter's syndrome. Pediatr Endocrinol Rev. 2014;12 Suppl 1:107–13. 
  12. Schulze-Frenking G, Jones SA, Roberts J, Beck M, Wraith JE. Effects of enzyme replacement therapy on growth in patients with mucopolysaccharidosis type II. J Inherit Metab Dis. 2011;34:203–8.
  13. Kamin W. Diagnosis and management of respiratory involvement in Hunter syndrome. Acta Paediatr Suppl. 2008 Apr. 97(457):57-60. 
  14. Chmielarz I, Gabig-Ciminska M, Malinowska M, Banecka-Majkutewicz Z, Wegrzyn A, Jakobkiewicz-Banecka J. Comparison of siRNA-mediated silencing of glycosaminoglycan synthesis genes and enzyme replacement therapy for mucopolysaccharidosis in cell culture studies. Acta Biochim Pol. 2012. 59(4):697-702. 
  15. Jurecka A, Krumina Z, Zuber Z, Rózdzynska-Swiatkowska A, Kloska A, Czartoryska B, et al. Mucopolysaccharidosis type II in females and response to enzyme replacement therapy. Am J Med Genet A. 2012 Feb. 158A(2):450-4.
  16. Guffon N, Bertrand Y, Forest I, Fouilhoux A, Froissart R. Bone marrow transplantation in children with Hunter syndrome: outcome after 7 to 17 years. J Pediatr. 2009;154:733–7.
  17. Annibali R, Caponi L, Morganti A, Manna M, Gabrielli O, Ficcadenti A. Hunter syndrome (Mucopolysaccharidosis type II), severe phenotype: long term follow-up on patients undergone to hematopoietic stem cell transplantation. Minerva Pediatr. 2013;65:487–96.

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Last updated: 2018-06-21 23:24