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Mucopolysaccharidosis 7

MPS 7


Presentation

  • Finally, there are also very mild cases that are discovered during adolescence or adulthood following presentation with thoracic kyphosis.[orpha.net]
  • Both isomers were present in equal amounts. The clinical features were similar to those of the Hurler syndrome or mucopolysaccharidoses type I (McKusick 1966).[onlinelibrary.wiley.com]
  • The data are being presented in poster and oral presentations by Dr. Emil Kakkis, Chief Executive Officer of Ultragenyx, at the 11 th Annual WORLD Symposium in Orlando, Florida.[globenewswire.com]
  • The data are being presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in Innsbruck, Austria.[healthcap.eu]
  • The severe form of MPS 7 can uniquely present at birth with hydrops fetalis (severe generalized edema). This is a very severe neonatal condition in which the child retains an enormous amount of fluid throughout the body.[ultragenyx.com]
Short Stature
  • Patients with MPS 7 may experience joint stiffness, short stature, an enlarged spleen and liver and heart / lung complications. MPS 7 also causes a characteristic facial appearance and can lead to a progressive skeletal dysplasia.[ultragenyx.com]
  • MPS VII causes various skeletal abnormalities that become more pronounced with age, including short stature and joint deformities (contractures) that affect mobility.[ghr.nlm.nih.gov]
  • He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay.[ggc.org]
  • MPS II is found almost exclusively in young males and is clinically characterized by short stature, hepatosplenomegaly, joint contractures, and coarse facies.[centogene.com]
Coarse Facial Features
  • Features of MPS VII are large head coarse facial features large tongue enlarged liver and spleen heart valve abnormalites umbilical hernia may have narrow airways cloudy cornea may have ear infections and hearing loss may have narrowing of the spinal[ldnz.org.nz]
  • The child had coarse facial features, corneal clouding, depressed nasal bridge, large tongue and high arched palate with a 2-cm mouth opening [Figure 1]. Parents did not reveal any history of snoring or apneic episodes while sleeping.[joacp.org]
  • The most common clinical manifestations of MPS I include the following: Characteristic coarse facial features Frequent upper-respiratory infections and otitis media Hepatosplenomegaly Inguinal or umbilical hernia Characteristic skeletal and joint findings[centogene.com]
  • Intralysosomal accumulation of these substrates results in pathological processes that produce a progressive dysfunction resulting in multiorgan deterioration that includes hepatosplenomegaly, dysostosis multiplex, short stature, coarse facial features[surgicalneurologyint.com]
Inguinal Hernia
  • Affected individuals also frequently develop an enlarged liver and spleen (hepatosplenomegaly), heart valve abnormalities, and a soft out-pouching around the belly-button (umbilical hernia ) or lower abdomen (inguinal hernia).[ghr.nlm.nih.gov]
  • Umbilical and inguinal hernias frequently occur in MPS due to abdominal protuberance from hepatosplenomegaly and ineffective connective tissue support of the anterior abdominal wall.[joacp.org]
  • hernia Frequent upper respiratory infections, otitis media, hearing loss Sleep apnea Cloudy corneas and vision loss.[centogene.com]
  • hernias, chronic diarrhoea, CTS [ 34 ], communicating hydrocephalus and spinal cord compression.[rheumatology.oxfordjournals.org]
Intravenous Administration
  • Ultragenyx initiated a Phase 1/2 study in the UK to evaluate the safety, tolerability, efficacy, and dose of intravenous administration of rhGUS in December 2013.[healthcap.eu]
  • The most common adverse events were consistent with the symptoms of MPS 7 or related to intravenous administration of the investigational therapy, including respiratory disorders, infections, and arthralgia.[globenewswire.com]
Fatigue
  • […] of UX003 study drug treatment ] The PedsQL 18-item scale is comprised of 3 dimensions: general fatigue (6 items), sleep/rest fatigue (6 items) and cognitive fatigue (6 items).[clinicaltrials.gov]
  • For the fatigue scores, four patients improved at or above the MID level after 24 weeks of treatment and nine of 12 showed improvement at some point during the study.[checkorphan.org]
Splenomegaly
  • Splenomegaly occurs in the hematopoietic system. Inborn mucopolysaccharide metabolic disorders due to β-glucuronidase deficiency with granular inclusions in granulocytes occurs in the biochemical and metabolic systems.[en.wikipedia.org]
  • […] 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]
Respiratory Disorders
  • The most common adverse events were consistent with the symptoms of MPS 7 or related to intravenous administration of the investigational therapy, including respiratory disorders, infections, and arthralgia.[globenewswire.com]
Pharyngitis
  • As the patients grow older, the deposition of glycosaminoglycans in the pharyngeal tissues and tracheal cartilages becomes larger, conditioning intraluminal narrows of the conductive airway, leading to increase difficulties in airway establishment.[omicsonline.org]
Failure to Thrive
  • […] to thrive, intellectual disability, and developmental delay.[ 5 12 ] The extensive storage of these glycosaminoglycans is also known to cause meningeal thickening.[ 4 ] Intraoperatively, our patient was noted to have thickened arachnoid membrane, which[surgicalneurologyint.com]
Hepatosplenomegaly
  • Clinical description Clinical signs are extremely variable: there are prenatal forms with non-immune hydrops fetalis, and severe neonatal forms with dysmorphism, hernias, hepatosplenomegaly, club feet, dysostosis, severe hypotonia and neurological disorders[orpha.net]
  • Affected individuals also frequently develop an enlarged liver and spleen (hepatosplenomegaly), heart valve abnormalities, and a soft out-pouching around the belly-button (umbilical hernia ) or lower abdomen (inguinal hernia).[ghr.nlm.nih.gov]
  • The Phase 3 study will also evaluate the safety and tolerability of rhGUS, pulmonary function, walking, stair climb, shoulder flexion, fine and gross motor function, hepatosplenomegaly, cardiac size and function, visual acuity, patient and caregiver assessment[biospace.com]
  • Coarse facies, mild dysostosis multiplex, hepatosplenomegaly and joint contractures may also be present. There is considerable variation in onset and severity of the clinical phenotype even within a sibship.[genedx.com]
  • MPS II is found almost exclusively in young males and is clinically characterized by short stature, hepatosplenomegaly, joint contractures, and coarse facies.[centogene.com]
Hepatomegaly
  • Hepatomegaly occurs in the gastrointestinal system. Splenomegaly occurs in the hematopoietic system.[en.wikipedia.org]
  • Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment.[genecards.org]
  • Somatic manifestations such as hepatomegaly, dysostosis multiplex, coarse facies and hypertrichosis are relatively mild compared to the other mucopolysaccharidoses.[invitae.com]
  • Ultrasound abdomen showed moderate hepatomegaly. The echocardiogram showed mitral valve prolapse with moderate mitral regurgitation and tricuspid valve collapse with mild tricuspid regurgitation.[neurologyindia.com]
  • Other 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[rheumatology.oxfordjournals.org]
Hearing Impairment
  • 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]
Hirsutism
  • Patient had virilization of the external genitalia with hirsutism and masculine voice. Patient had ambiguous genitalia. There was history of unexplained sibling death in the family at 1 year of age.[joacp.org]
Corneal Opacity
  • The symptoms include: in the head, neck, and face: coarse (Hurler-like) facies and macrocephaly, frontal prominence, premature closure of sagittal lambdoid sutures, and J-shaped sella turcica in the eyes: corneal opacity and iris coloboma in the nose:[en.wikipedia.org]
Hydrops Fetalis
  • More than half of infants with hydrops fetalis do not survive beyond early infancy. Some adults with MPS 7 can have a less severe physical or skeletal disease.[ultragenyx.com]
  • The most severe cases of MPS VII are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth.[ghr.nlm.nih.gov]
  • The most severe cases of MPS VII are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with this condition are stillborn or die soon after birth.[ldnz.org.nz]
  • Clinical description Clinical signs are extremely variable: there are prenatal forms with non-immune hydrops fetalis, and severe neonatal forms with dysmorphism, hernias, hepatosplenomegaly, club feet, dysostosis, severe hypotonia and neurological disorders[orpha.net]
  • Fetal deaths due to nonimmune hydrops fetalis have been noted. In mild cases, survival to age 19-20 years has been reported.[emedicine.medscape.com]
Macrocephaly
  • The features of MPS VII include a large head ( macrocephaly ), a buildup of fluid in the brain (hydrocephalus), distinctive-looking facial features that are described as " coarse ," and a large tongue ( macroglossia ).[ghr.nlm.nih.gov]
  • The symptoms include: in the head, neck, and face: coarse (Hurler-like) facies and macrocephaly, frontal prominence, premature closure of sagittal lambdoid sutures, and J-shaped sella turcica in the eyes: corneal opacity and iris coloboma in the nose:[en.wikipedia.org]
  • Other forms of MPS VII are less severe and present during early childhood and are characterized by the following signs and symptoms: Macrocephaly and hydrocephalus Distinctive facial features and macroglossia Hepatosplenomegaly Cardiac valve abnormalities[centogene.com]
Long Arm
  • arm of chromosome 7 (7q11.21; OMIM #253220).[emedicine.medscape.com]
  • The gene that causes MPS IIIA is located on the long arm of chromosome 17. MPS IIIB( Sanfilippo syndrome type B) is due to a deficiency in N-acetyl-alpha-D-glucosaminidase (NAG).[encyclopedia.com]
Joint Deformity
  • MPS VII causes various skeletal abnormalities that become more pronounced with age, including short stature and joint deformities (contractures) that affect mobility.[ghr.nlm.nih.gov]
Short Neck
  • Airway evaluation: abnormal neck anatomy, short neck with limited mobility, hyromental and thyromentonian distance less than 6 cm, severely limited jaw protrusion, mouth opening inferior to 6 cm, mallampati IV and snoring.[omicsonline.org]
  • She had dysmorphic facial features, macroglossia, a short neck, a low hair line, a high arched palate, corneal haziness, Mongolian spots over back, exaggerated thoracic kyphosis, and short stout fingers.[neurologyindia.com]
Frontal Bossing
  • Figure 1: (a - c) Magnetic resonance image showing scaphocephaly with frontal bossing and bilateral frontotemporal atrophy; (d - f) computed tomography surface shaded display showing craniosynostosis involving metopic, sagittal and bilateral lambdoid[neurologyindia.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]
  • He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay.[ggc.org]
  • In March, the drug failed a mid-stage study testing it as a seizure medication for Glut1 DS patients.[biopharmadive.com]
  • Additional clinical symptoms include intellectual disability, progressive neurologic symptoms including aggressive behavior, poor coordination, seizures and hearing loss.[genedx.com]
  • SEIZURES Seizures are a problem found in severe forms of MPS and especially in MPS III (Sanfilippo syndrome). Patients with seizures are given a type of prescription medication known as an anticonvulsant.[encyclopedia.com]

Workup

  • This would require addition to the CSF before workup, and the lack of stable isotope–labeled precursor molecules (GAGs) precludes this possibility.[clinchem.aaccjnls.org]
  • CASE REPORT The patient is a 6-year-old male who was referred to a pediatric clinic for an incidentally found CM-I and cervicothoracic syrinx [ Figure 1 ] identified during a preoperative workup prior to the surgical management of a progressive thoracolumbar[surgicalneurologyint.com]

Treatment

  • Changes from before treatment (baseline) to 24 weeks after treatment in each domain variable were scored against pre-specified MIDs.[clinicaltrials.gov]
  • All patients experienced treatment emergent adverse events, which were generally mild to moderate in severity. Six of the eight patients with infusion associated reactions (IARs) on rhGUS treatment had events involving the IV catheter.[checkorphan.org]
  • Management and treatment Multidisciplinary management allows adapted symptomatic treatment, which is essential for improving the quality of life of the patients. In late-onset forms, treatment is mainly orthopaedic.[orpha.net]
  • The use of enzyme replacement therapy as a potential treatment is based on 20 years of research work in murine models of the disease.[biospace.com]

Prognosis

  • Prognosis Prognosis is poor for antenatal forms, most often leading to death in utero. Neonatal and childhood forms have a very limited life expectancy, whereas milder forms have a prolonged survival.[orpha.net]
  • Prognosis Fetal deaths have been reported in severe cases. In patients with milder cases, survival to age 19-20 years has been reported.[emedicine.medscape.com]
  • The decision for surgery should be taking into account, the characterization of the metabolic disorder, its course, prognosis, and life expectancy.[neurologyindia.com]
  • Prognosis Life expectancy for individuals with an MPS is extremely varied.[encyclopedia.com]
  • With such an approach, current management options may alleviate some of the neurological symptoms of Hunter syndrome, but treatments that target accumulation of GAGs in the central nervous system are required if we hope to further improve the prognosis[touchneurology.com]

Etiology

  • Etiology The disease is caused by beta-D-glucuronidase deficiency, which leads to accumulation of several glycosaminoglycans (dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS)) in lysosomes.[orpha.net]

Epidemiology

  • Summary Epidemiology Less than 40 patients with neonatal to moderate presentation have been reported since the initial description of the disease by Sly in 1973.[orpha.net]
  • Epidemiology Frequency Sly syndrome is a rare form of mucopolysaccharidosis with an estimated worldwide frequency of 1 per 250,000 births. United States Sly syndrome is extremely rare in the United States, and few cases have been described.[emedicine.medscape.com]
  • Relevant External Links for GUSB Genetic Association Database (GAD) GUSB Human Genome Epidemiology (HuGE) Navigator GUSB Atlas of Genetics and Cytogenetics in Oncology and Haematology: GUSB No data available for Genatlas for GUSB Gene Identification and[genecards.org]
  • The overall frequency of either p.R59H or 1622-1627insG was 57.7% of the disease-causing alleles, and this epidemiological study suggested a carrier frequency of 1:58 for this population 31.[centogene.com]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology Mutations in the beta-glucuronidase ( GUSB ) gene cause Sly syndrome. This gene instructs the production of the beta-glucuronidase enzyme, which is involved in the breakdown of glycosaminoglycans (GAGs).[emedicine.medscape.com]
  • [Frontiers in Bioscience, Landmark, 22, 385-406, January 1, 2016] Mucopolysaccharidosis VI: Pathophysiology, diagnosis and treatment 1 UCSF Benioff Children’s Hospital Oakland, Department of Gastroenterology, Oakland, CA, USA, 2 BioMarin Pharmaceutical[bioscience.org]
  • A clear understanding of the pathophysiology is important for the management of such patients.[joacp.org]
  • Pathophysiology of the MPS disorders The MPSs are chronic and progressive syndromes that produce a spectrum of signs and symptoms in multiple organ systems. A good example of this is seen in individuals with MPS I.[rheumatology.oxfordjournals.org]

Prevention

  • Prevention No specific measures can prevent the gene mutations that cause MPS.[encyclopedia.com]
  • Maintenance steroid therapy intraoperatively prevents adrenal crisis. Daily cortisol production ranges from 9 to 11 mg/ m 2 /day. [18] Stress causes ACTH mediated increase in the cortisol production.[joacp.org]
  • Currently, HSCT with bone marrow or umbilical cord blood stem cells has been shown to prevent many of the clinical features of the severe phenotypes of MPS I, VI and VII [ 55–57 ].[rheumatology.oxfordjournals.org]
  • […] ganglion cells and loss of hair cells. 9,24 Carpal tunnel syndrome caused by entrapment of the median or ulnar nerves has been reported to affect 96 % of children who have Hunter syndrome but may be underdiagnosed, for patients’ cognitive impairment often prevents[touchneurology.com]
  • Preventing mucopolysaccharidosis type II (Hunter syndrome): PGD and establishing a Hunter (46, XX) stem cell line. Prenat Diagn. 2011 Jun 27. [Medline].[emedicine.medscape.com]

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