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Mucopolysaccharidosis, MPS-II(MPS2)

MedGen UID:
7734
Concept ID:
C0026705
Disease or Syndrome
Synonyms: Attenuated MPS (subtype; formerly known as mild MPS II); Hunter Syndrome; I2S deficiency; IDS deficiency; Iduronate 2-sulfatase deficiency; MPS 2; MPS2; Mucopolysaccharidosis type 2; Mucopolysaccharidosis type II; Mucopolysaccharidosis with skin involvement; Severe MPS II; SIDS deficiency; Sulfoiduronate sulfatase deficiency
SNOMED CT: Mucopolysaccharidosis, MPS-II (70737009); Hunter's syndrome (70737009); Sulfoiduronidate sulfatase deficiency (70737009); Iduronate 2-sulfatase deficiency (70737009); Hunter syndrome (70737009); Hunter disease (70737009); MPSII - Mucopolysaccharidosis type II (70737009); Mucopolysaccharidosis type II (70737009); MPS 2 - Mucopolysaccharidosis 2 (70737009); Deficiency of iduronate-2-sulfatase (70737009); Iduronate sulfatase deficiency (70737009); Sulfo-iduronate sulfatase deficiency (70737009)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): IDS (Xq28)
 
Monarch Initiative: MONDO:0010674
OMIM®: 309900
Orphanet: ORPHA79388

Disease characteristics

Excerpted from the GeneReview: Mucopolysaccharidosis Type II
Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation. The vast majority of affected individuals are male; on rare occasion heterozygous females manifest findings. Age of onset, disease severity, and rate of progression vary significantly among affected males. In those with early progressive disease, CNS involvement (manifest primarily by progressive cognitive deterioration), progressive airway disease, and cardiac disease usually result in death in the first or second decade of life. In those with slowly progressive disease, the CNS is not (or is minimally) affected, although the effect of GAG accumulation on other organ systems may be early progressive to the same degree as in those who have progressive cognitive decline. Survival into the early adult years with normal intelligence is common in the slowly progressing form of the disease. Additional findings in both forms of MPS II include: short stature; macrocephaly with or without communicating hydrocephalus; macroglossia; hoarse voice; conductive and sensorineural hearing loss; hepatosplenomegaly; dysostosis multiplex; spinal stenosis; and carpal tunnel syndrome. [from GeneReviews]
Authors:
Maurizio Scarpa   view full author information

Additional descriptions

From OMIM
Mucopolysaccharidosis II (MPS2) is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues, and organs. Patients with MPS II excrete excessive amounts of chondroitin sulfate B (dermatan sulfate) and heparitin sulfate (heparan sulfate) in the urine (McKusick, 1972; Wraith et al., 2008).  http://www.omim.org/entry/309900
From MedlinePlus Genetics
Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a condition that affects many different parts of the body. The condition occurs almost exclusively in boys, although it has been reported in a few girls. It is a progressively debilitating disorder; however, the rate of progression varies among affected individuals.

At birth, individuals with MPS II do not display any features of the condition. 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. Narrowing of the airway causes frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). As the disorder progresses, individuals need medical assistance to keep their airway open.

Many other organs and tissues are affected in people with MPS II. Individuals with this disorder often have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), a short neck, an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with MPS II usually have thick skin that is not very stretchy. Some affected individuals also have distinctive white skin growths that look like pebbles. Most people with this disorder develop hearing loss. Some individuals with MPS II develop problems with the light-sensitive tissue in the back of the eye (retina) and have reduced vision. Carpal tunnel syndrome commonly occurs in children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord. The heart is also significantly affected by MPS II, and many individuals develop heart valve problems. Heart valve abnormalities can cause the heart to become enlarged (ventricular hypertrophy) and can eventually lead to abnormalities in the heart's rhythm (arrhythmia) and heart failure.

Children with MPS II grow steadily until about age 5, and then their growth slows and they develop short stature. Individuals with this condition have joint deformities (contractures) that significantly affect mobility. Most people with MPS II also have dysostosis multiplex, which refers to multiple skeletal abnormalities that can be seen on x-rays. Dysostosis multiplex includes a generalized thickening of certain bones, particularly the ribs.

There are two types of MPS II: the neuropathic form, which is more severe, and the non-neuropathic form, which is less severe. While both types affect many different organs and tissues as described above, people with neuropathic MPS II also experience a decline in intellectual function and a more rapid disease progression. Individuals with this form begin to lose basic functional skills (developmentally regress) between the ages of 6 and 8. Their life expectancy is 10 to 20 years. Individuals with non-neuropathic MPS II also have a shortened lifespan, but they typically live into adulthood, and their intelligence is not affected. Heart disease and airway obstruction are major causes of death in people with both types of MPS II.  https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-ii

Clinical features

From HPO
Dermatan sulfate excretion in urine
MedGen UID:
343207
Concept ID:
C1854774
Finding
An increased concentration of dermatan sulfate in the urine.
Heparan sulfate excretion in urine
MedGen UID:
340721
Concept ID:
C1854827
Finding
An increased concentration of heparan sulfates in the urine.
Urinary glycosaminoglycan excretion
MedGen UID:
871129
Concept ID:
C4025598
Finding
Excretion of glycosaminoglycan in the urine. Glycosaminoglycans are long unbranched polysaccharides consisting of a repeating disaccharide unit.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middle fingers as far as oligo- or monodactyl hands.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Abnormal heart valve morphology
MedGen UID:
892837
Concept ID:
C0241654
Finding
Any structural abnormality of a cardiac valve.
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Mild short stature
MedGen UID:
461427
Concept ID:
C3150077
Finding
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Intestinal pseudo-obstruction
MedGen UID:
5864
Concept ID:
C0021847
Disease or Syndrome
A functional rather than mechanical obstruction of the intestines, associated with manifestations that resemble those caused by an intestinal obstruction, including distension, abdominal pain, nausea, vomiting, constipation or diarrhea, in an individual in whom a mechanical blockage has been excluded.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Progressive loss of neural cells and tissue.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Sleep apnea
MedGen UID:
11458
Concept ID:
C0037315
Disease or Syndrome
An intermittent cessation of airflow at the mouth and nose during sleep is known as sleep apnea. Apneas that last at least 10 seconds are considered significant, but individuals with sleep apnea may experience apneas lasting from 20 seconds up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep.
Obstructive sleep apnea syndrome
MedGen UID:
101045
Concept ID:
C0520679
Disease or Syndrome
Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003).
Cervical cord compression
MedGen UID:
167271
Concept ID:
C0852866
Finding
Compression of the spinal cord in the cervical region, generally manifested by paresthesias and numbness, weakness, difficulty walking, abnormalities of coordination, and neck pain or stiffness.
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Isolated scaphocephaly
MedGen UID:
82712
Concept ID:
C0265534
Congenital Abnormality
Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Dysostosis multiplex
MedGen UID:
1851010
Concept ID:
C5848292
Disease or Syndrome
Airway obstruction
MedGen UID:
1387
Concept ID:
C0001883
Disease or Syndrome
Obstruction of conducting airways of the lung.
Tracheobronchomalacia
MedGen UID:
137939
Concept ID:
C0340231
Disease or Syndrome
Williams-Campbell syndrome is a congenital disorder characterized by severe bronchiectasis and recurrent pulmonary infections caused by a cartilage abnormality involving the 4th-6th order subsegmental bronchi. It typically presents in infancy or childhood with symptoms of coughing, wheezing, and dyspnea. Imaging reveals normal central airways with severe bilateral cystic bronchiectasis in the subsegmental bronchi, often associated with bronchial wall thickening, mucous plugging, and bronchomalacia. During dynamic imaging, the abnormal bronchi will demonstrate ballooning on inspiratory imaging and collapse/air-trapping on expiratory imaging (summary by Marini et al., 2017).
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Decreased iduronate sulfatase level
MedGen UID:
1814356
Concept ID:
C5676791
Finding
An decreased level of iduronate-2-sulfatase activity in the blood circulation.
Hoarse voice
MedGen UID:
5602
Concept ID:
C0019825
Sign or Symptom
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Widely spaced teeth
MedGen UID:
337093
Concept ID:
C1844813
Finding
Increased spaces (diastemata) between most of the teeth in the same dental arch.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Hypertrichosis
MedGen UID:
43787
Concept ID:
C0020555
Disease or Syndrome
Hypertrichosis is increased hair growth that is abnormal in quantity or location.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Optic papillitis
MedGen UID:
10565
Concept ID:
C0030353
Finding
Papilledema refers to edema (swelling) of the optic disc secondary to any factor which increases cerebral spinal fluid pressure.
Abnormality of retinal pigmentation
MedGen UID:
350681
Concept ID:
C1862475
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMucopolysaccharidosis, MPS-II

Professional guidelines

PubMed

Yee KS, Alexanderian D, Merberg D, Natarajan M, Wang S, Wu Y, Whiteman DAH
Mol Genet Metab 2023 Nov;140(3):107652. Epub 2023 Jul 13 doi: 10.1016/j.ymgme.2023.107652. PMID: 37506513
Scott CR, Elliott S, Hong X, Huang JY, Kumar AB, Yi F, Pendem N, Chennamaneni NK, Gelb MH
J Pediatr 2020 Jan;216:204-207. Epub 2019 Nov 12 doi: 10.1016/j.jpeds.2019.09.036. PMID: 31732130Free PMC Article
Zareba G
Drugs Today (Barc) 2007 Nov;43(11):759-67. doi: 10.1358/dot.2007.43.11.1157619. PMID: 18174963

Curated

Beck M, Wijburg FA, Gal A
Eur J Hum Genet 2012 Jan;20(1) Epub 2011 Aug 24 doi: 10.1038/ejhg.2011.143. PMID: 21863056Free PMC Article

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Iduronate 2-Sulfatase Deficiency, Mucopolysaccharidosis Type II, 2022

American College of Medical Genetics and Genomics, Algorithm, Mucopolysacchardosis Type II (MPSII): Decreased Iduronate 2-Sulfatase (I2S) activity, 2022

Recent clinical studies

Etiology

Muenzer J, Burton BK, Amartino HM, Harmatz PR, Gutiérrez-Solana LG, Ruiz-Garcia M, Wu Y, Merberg D, Alexanderian D, Jones SA
Orphanet J Rare Dis 2023 Nov 16;18(1):357. doi: 10.1186/s13023-023-02805-3. PMID: 37974184Free PMC Article
Vollebregt AAM, Ebbink BJ, Rizopoulos D, Lequin MH, Aarsen FK, Shapiro EG, van der Ploeg AT, van den Hout JMP
J Inherit Metab Dis 2021 May;44(3):751-762. Epub 2021 Jan 25 doi: 10.1002/jimd.12342. PMID: 33330992Free PMC Article
Scott CR, Elliott S, Hong X, Huang JY, Kumar AB, Yi F, Pendem N, Chennamaneni NK, Gelb MH
J Pediatr 2020 Jan;216:204-207. Epub 2019 Nov 12 doi: 10.1016/j.jpeds.2019.09.036. PMID: 31732130Free PMC Article
Vedolin L, Schwartz IV, Komlos M, Schuch A, Puga AC, Pinto LL, Pires AP, Giugliani R
AJNR Am J Neuroradiol 2007 Jun-Jul;28(6):1029-33. doi: 10.3174/ajnr.A0510. PMID: 17569950Free PMC Article

Diagnosis

Sofronova V, Gurinova E, Petukhova D, Fukamatsu H, Yamamoto T, Aoyama Y, Golikova P, Moskvitin G, Ivanova R, Savvina M, Vasilev F, Moriwaki T, Terawaki S, Sukhomyasova A, Maksimova N, Otomo T
Int J Mol Sci 2023 Mar 15;24(6) doi: 10.3390/ijms24065647. PMID: 36982718Free PMC Article
Wang J, Bhalla A, Ullman JC, Fang M, Ravi R, Arguello A, Thomsen E, Tsogtbaatar B, Guo JL, Skuja LL, Dugas JC, Davis SS, Poda SB, Gunasekaran K, Costanzo S, Sweeney ZK, Henry AG, Harris JM, Henne KR, Astarita G
Int J Mol Sci 2020 Jul 30;21(15) doi: 10.3390/ijms21155449. PMID: 32751752Free PMC Article
Scott CR, Elliott S, Hong X, Huang JY, Kumar AB, Yi F, Pendem N, Chennamaneni NK, Gelb MH
J Pediatr 2020 Jan;216:204-207. Epub 2019 Nov 12 doi: 10.1016/j.jpeds.2019.09.036. PMID: 31732130Free PMC Article
Vedolin L, Schwartz IV, Komlos M, Schuch A, Puga AC, Pinto LL, Pires AP, Giugliani R
AJNR Am J Neuroradiol 2007 Jun-Jul;28(6):1029-33. doi: 10.3174/ajnr.A0510. PMID: 17569950Free PMC Article

Therapy

Muenzer J, Vijayaraghavan S, Stein M, Kearney S, Wu Y, Alexanderian D
Genet Med 2022 Jul;24(7):1437-1448. Epub 2022 May 20 doi: 10.1016/j.gim.2022.04.002. PMID: 35588317
Vollebregt AAM, Ebbink BJ, Rizopoulos D, Lequin MH, Aarsen FK, Shapiro EG, van der Ploeg AT, van den Hout JMP
J Inherit Metab Dis 2021 May;44(3):751-762. Epub 2021 Jan 25 doi: 10.1002/jimd.12342. PMID: 33330992Free PMC Article

Prognosis

Vollebregt AAM, Ebbink BJ, Rizopoulos D, Lequin MH, Aarsen FK, Shapiro EG, van der Ploeg AT, van den Hout JMP
J Inherit Metab Dis 2021 May;44(3):751-762. Epub 2021 Jan 25 doi: 10.1002/jimd.12342. PMID: 33330992Free PMC Article
Vedolin L, Schwartz IV, Komlos M, Schuch A, Puga AC, Pinto LL, Pires AP, Giugliani R
AJNR Am J Neuroradiol 2007 Jun-Jul;28(6):1029-33. doi: 10.3174/ajnr.A0510. PMID: 17569950Free PMC Article

Clinical prediction guides

Muenzer J, Burton BK, Amartino HM, Harmatz PR, Gutiérrez-Solana LG, Ruiz-Garcia M, Wu Y, Merberg D, Alexanderian D, Jones SA
Orphanet J Rare Dis 2023 Nov 16;18(1):357. doi: 10.1186/s13023-023-02805-3. PMID: 37974184Free PMC Article
Sofronova V, Gurinova E, Petukhova D, Fukamatsu H, Yamamoto T, Aoyama Y, Golikova P, Moskvitin G, Ivanova R, Savvina M, Vasilev F, Moriwaki T, Terawaki S, Sukhomyasova A, Maksimova N, Otomo T
Int J Mol Sci 2023 Mar 15;24(6) doi: 10.3390/ijms24065647. PMID: 36982718Free PMC Article
Vollebregt AAM, Ebbink BJ, Rizopoulos D, Lequin MH, Aarsen FK, Shapiro EG, van der Ploeg AT, van den Hout JMP
J Inherit Metab Dis 2021 May;44(3):751-762. Epub 2021 Jan 25 doi: 10.1002/jimd.12342. PMID: 33330992Free PMC Article
Vedolin L, Schwartz IV, Komlos M, Schuch A, Puga AC, Pinto LL, Pires AP, Giugliani R
AJNR Am J Neuroradiol 2007 Jun-Jul;28(6):1029-33. doi: 10.3174/ajnr.A0510. PMID: 17569950Free PMC Article

Supplemental Content

Table of contents

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Iduronate 2-Sulfatase Deficiency, Mucopolysaccharidosis Type II, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Mucopolysacchardosis Type II (MPSII): Decreased Iduronate 2-Sulfatase (I2S) activity, 2022
    • EuroGenetest, 2011
      Clinical utility gene card for: mucopolysaccharidosis type II.

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