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:

• 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 papular skin lesions on the upper back and sides of the upper arms [11]
• Protuberant abdomen
• Diarrhea
• Short stature [12]
• Skeletal deformities
• Joint stiffness
• Inguinal or umbilical hernia
• Developmental delay
• Intellectual disability
• Hyperactivity
• Seizures
• Hepatomegaly
• Cardiomyopathy
• Cardiac valve dysplasia
• Carpal tunnel syndrome
• Communicating hydrocephalus
• Pulmonary hypertension
• Hip dysplasia
• Airway obstruction
• Spinal stenosis

The presentation of MPS 2B usually occurs in adolescence or adulthood. 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 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]

  Noninflammatory retina disease 0000488 Sensorineural hearing impairment 0000407 Short attention span Poor attention span Problem paying attention [ more ] 0000736 Sleep apnea Pauses in breathing while sleeping 0010535 Sleep-wake cycle disturbance 0006979 Splenomegaly [rarediseases.info.nih.gov]

• Short Stature

  Early bone involvement leads to decreased growth velocity and short stature in nearly all patients. [ncbi.nlm.nih.gov]

  […] 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]

  Clinical features and disease severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities and facial dysmorphism. [news-medical.net]

  0030799 Severe short stature Dwarfism Proportionate dwarfism Short stature, severe [ more ] 0003510 Short neck Decreased length of neck 0000470 Split hand Claw hand Claw hand deformities Claw hands Claw-hand deformities Split-hand [ more ] 0001171 Thick [rarediseases.info.nih.gov]

• 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]

  In some cases of Hunter syndrome, central nervous system involvement leads to developmental delays and nervous system problems. [hunterpatients.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]

• Dysostosis

  Most patients presenting beyond the neonatal period have increased urinary glycosaminoglycans and dysostosis multiplex. [news-medical.net]

  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]

  This disorder is characterized by mental retardation, coarse faces, short stature, hearing loss, hydrocephalus, hepatosplenomegaly, dysostosis multiplex, airway obstruction, and cardiac valve disease. [genome.jp]

• 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]

  Hernias, clouding of the corneas, excessive accumulation of cerebrospinal fluid in the skull (hydrocephalus), short stature, heart disease, and coarse facial features have also been reported. [rarediseases.org]

  Symptoms usually become apparent between three and eight years of age and include coarse facial features, corneal clouding, joint stiffness, short stature and hepatosplenomegaly. Survival to adulthood is common. [news-medical.net]

• 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]

  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. [consultant360.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]

  […] voice Hoarseness Husky voice [ more ] 0001609 Inguinal hernia 0000023 Irregularity of vertebral bodies 0004582 Macroglossia Abnormally large tongue Increased size of tongue Large tongue [ more ] 0000158 Peripheral visual field loss Loss of peripheral [rarediseases.info.nih.gov]

• Nasal Congestion

  Signs of a related sinus or respiratory infection may include: cough fever headache nasal congestion sinus pain With a skin infection, mucormycosis can develop within any part of your body. [healthline.com]

  Signs & Symptoms The most common presentation is a sinus infection (sinusitis) that is accompanied by nasal congestion, nasal discharge, and sinus pain. A fever and headache can also occur. [rarediseases.org]

  The most frequently reported AEs included fever, headache, cough, pharyngitis, upper respiratory tract infection, nasal congestion, nausea, vomiting, abdominal pain, and diarrhea. The majority of AEs were mild or moderate in severity in all groups. [nature.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]

• Delayed Speech Development

  Coarse facial features, hepatomegaly, hearing difficulties and delayed speech development are common. Life expectancy in attenuated forms may be limited to Figure 4b ). [touchophthalmology.com]

• Tonsillar Hypertrophy

  In another, we carried out tonsillar volumetric reduction through radiofrequency, with recurrence of symptoms and tonsillar hypertrophy exploration of grade III/IV. [elsevier.es]

• 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]

  It is characterised by excretion of dermatan sulfate in the urine, growth retardation, lumbar kyphosis, sternal protrusion, genu valgum, usually hepatosplenomegaly, and no mental retardation. Onset occurs after two years of age. [kmle.co.kr]

  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]

  Features include coarse facial appearance, short stature, hepatosplenomegaly, intellectual disability and joint stiffness. [ggc.org]

  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]

• 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]

  Sistemik muayenede korneal bulutlanma (11 olgu) işitme kaybı (5 olgu), hepatomegali (4 olgu), adenoid hipertrofi (opere edilmiş 4 olgu), kardiyak tutulum (9 olgu), tüm hastalarda kemik incelemede disostozis multipleks bulguları saptandı. [egetipdergisi.com.tr]

  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]

• Aggressive Behavior

  The symptoms include aggressive behavior, hyperactivity, mental function decline, severe intellectual disability and spasticity. [secure.ssa.gov]

  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]

  Your child may also behave aggressively and seem unable to sense danger. As your child's overall physical functioning declines, these behavior problems tend to become less severe. Seizures also may occur in children with Hunter syndrome. [mayoclinic.org]

  behavior Aggression Aggressive behaviour Aggressiveness [ more ] 0000718 Arrhythmia Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ] 0011675 Hypertension 0000822 Impulsivity Impulsive 0100710 Large central [rarediseases.info.nih.gov]

• 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]

• Hyperactivity

  Children are often goes unrecognized or misdiagnosed as having idiopathic developmental/speech delay, attention deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorders. [anadolupsikiyatri.net]

  The symptoms include aggressive behavior, hyperactivity, mental function decline, severe intellectual disability and spasticity. [secure.ssa.gov]

  A prominent feature is neurological damage that presents as developmental delay and hyperactivity but progresses to mental retardation and dementia. [uniprot.org]

  […] 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 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]

• Seizure

  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]

  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]

  He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay. [ggc.org]

  Seizure 0001250 Stereotypy Repetitive movements Repetitive or self-injurious behavior [ more ] 0000733 Percent of people who have these symptoms is not available through HPO Abnormal heart valve morphology 0001654 Asthma 0002099 Cervical cord compression [rarediseases.info.nih.gov]

• 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]

  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]

  Some severe problems, such as hydrocephalus, are more common in neuronopathic disease, whereas others disorders (such as carpal tunnel syndrome and spinal cord compression) are equally likely in both forms of the condition. 15 Chronic communicating hydrocephalus [touchneurology.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]

• Cervical Cord Compression

  compression Pressure on spinal cord 0002176 Temporomandibular joint ankylosis Freezing of jaw joint 0012478 Upper airway obstruction 0002781 Wide nasal bridge Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose [rarediseases.info.nih.gov]

• 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]

• Abdominal Pain

  […] include: Cough Coughing blood (occasionally) Fever Shortness of breath Symptoms of gastrointestinal mucormycosis include: Abdominal pain Blood in the stools Diarrhea Vomiting blood Symptoms of kidney (renal) mucormycosis include: Fever Pain in the upper [medlineplus.gov]

  Symptoms can include abdominal pain and vomiting of blood (hematemesis). Lesions can develop that cause a hole to form in the stomach or intestines (perforation). [rarediseases.org]

  The most frequently reported AEs included fever, headache, cough, pharyngitis, upper respiratory tract infection, nasal congestion, nausea, vomiting, abdominal pain, and diarrhea. The majority of AEs were mild or moderate in severity in all groups. [nature.com]

  The most frequently reported AEs during the study (with a excess incidence of at least a 9% compared with placebo in either idursulfase treated group) included headache, nasopharyngitis, abdominal pain, arthralgia and pruritus. [cochranelibrary.com]

• Abdominal Distension

  Color Doppler ultrasound of the abdomen showed no hepatosplenomegaly although abdominal distension was obvious. The boy also showed no impaired mental or psychomotor development. Neither of his parents showed any symptoms. [journals.lww.com]

  distension associated with thoracic deformities.5,7 The nervous system is also commonly affected in some types of MPS, and results in the occurrence of neural and/or spinal cord compression, eventually leading to cognitive impairment.8,9 These changes [scielo.br]

• Macroglossia

  Oropharyngeal and tracheobronchial deposition of glycosaminoglycans results in airway obstruction due to macroglossia, supraglottic narrowing, and tracheomalacia. [symptoma.com]

  An enlarged tongue (macroglossia) and narrowing of the trachea results in upper respiratory infections and sleep apnea. As the syndrome develops, patients need medical assistance to keep their airway open. [transparencymarketresearch.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]

  DS, HS α-L-Iduronidase MPS I H/S Hurler-Scheie syndrome Intermediate phenotype, macrocephaly, macroglossia, joint limitations. [hindawi.com]

• Widely Spaced Teeth

  spaced teeth Wide-spaced teeth Widely-spaced teeth [ more ] 0000687 X-linked recessive inheritance 0001419 [rarediseases.info.nih.gov]

• 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]

  pigmentation 0007703 Cardiomyopathy Disease of the heart muscle 0001638 Communicating hydrocephalus 0001334 Constrictive median neuropathy 0012185 Corneal opacity 0007957 Global developmental delay 0001263 Hip dysplasia 0001385 Hip osteoarthritis 0008843 [rarediseases.info.nih.gov]

• Joint Stiffness

  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. [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]

  […] sulfatase enzyme in blood serum or cells Heart murmur and leaky heart valves Enlarged 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 [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]

  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]

• Genu Valgum

  valgum, usually hepatosplenomegaly, and no mental retardation; onset occurs after 2 years of age. [drugs.com]

  It is characterised by excretion of dermatan sulfate in the urine, growth retardation, lumbar kyphosis, sternal protrusion, genu valgum, usually hepatosplenomegaly, and no mental retardation. Onset occurs after two years of age. [kmle.co.kr]

  Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. [novapublishers.org]

  MPS IVA patients with genu valgum, total (000s) Table 17. MPS IVA patients with eye problems, total (000s) Table 18. MPS IVA patients with a history of ear infections, total (000s) Table 19. [giikorea.co.kr]

  valgum, hypermobile joints Waddling gait with frequent falls Qualitative urine glycosaminoglycan (GAG) analysis demonstrates keratan sulfate and chondroitin 6-sulfate. [centogene.com]

• Severe Short Stature

  0030799 Severe short stature Dwarfism Proportionate dwarfism Short stature, severe [ more ] 0003510 Short neck Decreased length of neck 0000470 Split hand Claw hand Claw hand deformities Claw hands Claw-hand deformities Split-hand [ more ] 0001171 Thick [rarediseases.info.nih.gov]

• 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]

  Both the children had a history of recurrent respiratory infections and intermittent joint pain since early childhood. On examination, they had short stature, big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers. [mjdrdypu.org]

• Hypertrichosis

  Other symptoms may include carpal tunnel syndrome, coarse facial features, deafness, hairy body (hypertrichosis), joint stiffness, and a large head (macrocephaly). [secure.ssa.gov]

  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]

  Additional dermatological findings include hypertrichosis, thickened skin, and multiple Mongolian spots. Hypertrichosis may result in synophrys. [emedicine.medscape.com]

  […] more ] 0000268 Flexion contracture Flexed joint that cannot be straightened 0001371 Hearing impairment Deafness Hearing defect [ more ] 0000365 Heparan sulfate excretion in urine 0002159 Hydrocephalus Too much cerebrospinal fluid in the brain 0000238 Hypertrichosis [rarediseases.info.nih.gov]

• Coarseness of the Skin

  The clinical features are limited to short stature, a large head, a short neck, coarse facial features, skin eruptions, and mild mental retardation with normal intelligence, anterior open bite due to enlarged tongue suggested of mucopolysaccharidosis. [jnsbm.org]

• Skin Thickening

  thickening, claw and shortened fingers (bradydactyly) with painless nodules. [amhsr.org]

• 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]

  impairment Conductive deafness Conductive hearing loss [ more ] 0000405 Contractures of the large joints 0005781 Decreased nerve conduction velocity 0000762 Developmental regression Loss of developmental milestones Mental deterioration in childhood [ [rarediseases.info.nih.gov]

• Hearing Problem

  Problems usually start before age 3, and common presenting features include: Coarsening of facial features. Thickening of the tongue. Decline in intellectual function. Hearing problems. Swollen and stiff joints. Abdominal hernias. [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]

• Short Neck

  There is often 'pebbling' of the skin over the neck and chest. Joint stiffness, short stature, and skeletal deformities are common. Many have short necks, a protuberant abdomen, a broad chest, and facial coarseness. [disorders.eyes.arizona.edu]

  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]

  […] delays resulting in short stature. [rarediseases.org]

• 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]

  […] vermilion border Full lips Increased volume of lip Plump lips Prominent lips Thick lips [ more ] 0012471 Umbilical hernia 0001537 5%-29% of people have these symptoms Abnormal aortic morphology 0001679 Abnormal epiphyseal ossification 0010656 Abnormal [rarediseases.info.nih.gov]

• Broad Nasal Bridge

  bridge Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal [rarediseases.info.nih.gov]

• 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]

  This disorder is characterized by mental retardation, coarse faces, short stature, hearing loss, hydrocephalus, hepatosplenomegaly, dysostosis multiplex, airway obstruction, and cardiac valve disease. [genome.jp]

  At the age of 3 years 6 months, she had a coarse face, hearing loss, hepatosplenomegaly, severe thoracolumbar kyphosis, limitations of joint mobility, mental retardation, and mitroaortic valvular dysplasia, but no corneal clouding. [jmg.bmj.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]

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:

• Echocardiogram
• Pulmonary function testing [13]
• Sleep study 
• Hearing test
• Nerve conduction velocity for carpal tunnel syndrome
• CT or MRI of the brain stem and cervical spine and lumbar puncture to assess for hydrocephalus and spinal cord compression
• Eye examination with slit lamp to assess visual acuity and corneal and retinal disease
• Developmental assessment

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

• Enlargement of the Spleen

  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]

  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]

  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]

  Patients with this disorder often develop an enlarged liver and spleen (hepatosplenomegaly), a large head (macrocephaly) and fluid buildup in the brain (hydrocephalus), umbilical hernia or lower abdomen hernia (inguinal hernia). [transparencymarketresearch.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 / [sangamo.com]

• 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]

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.

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.

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].

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.

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.

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

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.

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.

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