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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]
Short Stature
  • Early bone involvement leads to decreased growth velocity and short stature in nearly all patients.[ncbi.nlm.nih.gov]
  • He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay.[ggc.org]
  • 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]
  • 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]
  • Short stature is usually not noted until after age 3 years.[emedicine.medscape.com]
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]
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]
  • 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]
  • They also had characteristic features of Hunter syndrome such as stunted growth, coarse facial features (large forehead, thick neck, tongue and lips, bushy eyebrows, and flattened nose), hearing loss, joint stiffness, poor peripheral vision, thickening[mjdrdypu.org]
Developmental Delay
  • He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay.[ggc.org]
  • 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]
  • In addition to developing somatic symptoms, patients having the neuronopathic form of the disease also display developmental delay and cognitive impairment in early childhood that progressively worsens and that is severely life-limiting.[touchneurology.com]
  • 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 an abnormal 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]
  • Most people with MPS II also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Dysostosis multiplex includes a generalized thickening of most long bones, particularly the ribs.[ghr.nlm.nih.gov]
  • 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]
  • The clinical signs are similar to those found in the Hurler syndrome, although no corneal clouding is observed and dysostosis is generally less prominent.[karger.com]
  • Musculoskeletal findings include dysostosis multiplex and thoracolumbar kyphosis, and the trunk appears short in length when compared to the length of the extremities. Joint mobility is decreased, and the fingers may have clawlike deformities.[emedicine.medscape.com]
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]
  • 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]
  • 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]
  • 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]
  • 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]
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]
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]
  • Diet A dietician can help you create a nutrition plan to help your baby control diarrhea and constipation, which may occur in those with severe MPS II.[babysfirsttest.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; • Narrowing of the cervical spinal canal (spinal stenosis); • Enlarged tongue (macroglossia) and vocal cords; • Enlarged liver and spleen (hepatosplenomegaly); • Contractures of the joints; • Leaky heart valves[secure.ssa.gov]
  • 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]
  • 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]
  • 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]
Hepatosplenomegaly
  • Enzyme replacement therapy (ERT) using idursulfase (Elaprase ) was conducted to the patient and it improved hepatosplenomegaly, white blood cells and platelets number, and decreased the level of urinary glycosaminoglycan.[ncbi.nlm.nih.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]
  • Physical findings: • Coarse facial features; • Narrowing of the cervical spinal canal (spinal stenosis); • Enlarged tongue (macroglossia) and vocal cords; • Enlarged liver and spleen (hepatosplenomegaly); • Contractures of the joints; • Leaky heart valves[secure.ssa.gov]
  • 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]
Hepatomegaly
  • The phenotype of the patient was severe, including joint stiffness, kyphosis, hepatomegaly, hypertrophic cardiomyopathy, moderate mental retardation, and bilateral hearing loss.[ncbi.nlm.nih.gov]
  • 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]
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]
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]
  • Neurological signs and symptoms that may be evident in patients having either the neuronopathic or non-neuronopathic phenotypes include seizures, optic nerve compression, hearing impairment, sleep apnoea, hydrocephalus, carpal tunnel syndrome, spinal[touchneurology.com]
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]
Joint Stiffness
  • Skeletal irregularities, vision problems, heart problems, diarrhea, joint stiffness, stunted growth and delayed development may be present.[symptoma.com]
  • The phenotype of the patient was severe, including joint stiffness, kyphosis, hepatomegaly, hypertrophic cardiomyopathy, moderate mental retardation, and bilateral hearing loss.[ncbi.nlm.nih.gov]
  • In both forms, symptoms include: Carpal tunnel syndrome Coarse features of the face Deafness (gets worse over time) Increased hair growth Joint stiffness Large head A physical exam and tests may show: Abnormal retina (back of the eye) Decreased iduronate[medlineplus.gov]
  • 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]
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]
  • Individuals with this disorder often have a large head ( macrocephaly ), a buildup of fluid in the brain (hydrocephalus), an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia ) or lower abdomen[ghr.nlm.nih.gov]
Skeletal Dysplasia
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]
  • 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]
  • 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]
  • 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]
  • 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]
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]
Seizure
  • In addition, both had features not commonly seen in this disorder, e.g. early onset of seizures in one patient and ptosis in the other.[ncbi.nlm.nih.gov]
  • Tonic–clonic seizures are the most common type of seizure in Hunter syndrome, but absent and myoclonic seizures have also been reported. 15 It is possible that absence seizures (petit mal) are under-reported; neurologists should be aware of this and seek[touchneurology.com]
  • He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay.[ggc.org]
  • 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]
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 can be effectively treated by insertion of a ventriculoperitoneal shunt, which can improve motor development in early stages of the disease. 17 It is suggested that nerve conduction studies be performed in patients every 1[touchneurology.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 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]
  • 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]
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]
  • In the early-onset, severe form, symptoms include: Aggressive behavior Hyperactivity Mental function gets worse over time Severe intellectual disability Jerky body movements In the late (mild) form, there can be mild to no mental deficiency.[medlineplus.gov]
  • […] in neuronopathic disease, can cause patients to become frustrated and may exacerbate behavioural difficulties. 9,15 Hyperactivity may appear to lesson with age, but this is usually because patients becoming increasingly physically disabled as the disease[touchneurology.com]
  • 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]
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]
  • 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]

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 Enlarged spleen Hernia in the groin Joint contractures (from joint stiffness) Tests may include: Enzyme study Genetic testing for a change in the iduronate sulfatase gene Urine test for heparan sulfate and dermatan sulfate The medicine called idursulfase[medlineplus.gov]
  • Individuals with this disorder often have a large head ( macrocephaly ), a buildup of fluid in the brain (hydrocephalus), an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia ) or lower abdomen[ghr.nlm.nih.gov]

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.
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Last updated: 2019-07-11 20:43