Clinical characteristics.

Individuals with mucopolysaccharidosis type VII (MPS VII) can present perinatally with early demise, nonimmune hydrops fetalis, cholestatic jaundice, and hepatosplenomegaly, or in early childhood with developmental delay and characteristic musculoskeletal features (e.g., short neck, short-trunk short stature, pectus deformity, gibbus, and joint stiffness/contractures) and craniofacial features (e.g., macrocephaly, coarse hair, coarse facies, corneal clouding, and macroglossia). Skeletal survey shows features of dysostosis multiplex including thickened cortical bone, abnormal J-shaped sella turcica, paddle- or oar-shaped ribs, short, thickened clavicles, platyspondyly with anterior beaking of the lower thoracic and lumbar vertebrae, and proximal pointing of the metacarpals and metatarsals. Complications include developmental delay, intellectual disability, hepatosplenomegaly, spinal stenosis, recurrent otitis media, hearing loss, pulmonary disease, obstructive sleep apnea, hernias, feeding difficulties, and heart valve disease.

Diagnosis/testing.

The diagnosis of MPS VII is established in a proband with characteristic clinical and radiographic findings, urine glycosaminoglycan (GAG) analysis with elevated concentrations of total GAGs with increased dermatan and chondroitin sulfate, and absent or reduced beta-glucuronidase enzyme activity in leukocytes, fibroblasts, or dried blood spots; and/or biallelic pathogenic variants in GUSB identified by molecular genetic testing.

Management.

Targeted therapy: Enzyme replacement therapy with vestronidase alfa.

Supportive care: Neonatal intensive care for infants with nonimmune hydrops fetalis; surgical fusion for atlantoaxial instability, surgery as needed for scoliosis, spine monitoring during surgery; anti-inflammatory medications and/or analgesics as needed for pain due to joint stiffness; physical medicine and rehabilitation, physical therapy, and occupational therapy for issues with mobility and activities of daily living; surgical decompression for spinal stenosis, wrist splints and surgery for carpal tunnel syndrome; early intervention services, speech therapy, and school support for developmental issues; tonsillectomy and adenoidectomy for airway obstruction and sleep apnea; positive pressure ventilation as needed; pulmonary toilet for restrictive lung disease; tympanostomy tubes and hearing aids for hearing loss; treatment per ophthalmologist for corneal clouding; thickeners and gastrostomy tube placement as needed for feeding difficulties; surgical repair for hernia; treatment of cardiac disease per cardiologist; hospice care when needed.

Surveillance: Urine dermatan and chondroitin sulfate levels every six to 12 months in individuals on enzyme replacement therapy; assess growth parameters every six to 12 months throughout childhood, then annually; developmental assessment every six to 12 months throughout childhood; orthopedic evaluation annually with radiographs per orthopedist; rehabilitation medicine evaluation as needed; neurologic exam and spine MRI annually throughout childhood and then every two years or per orthopedist in those who have had spinal decompression; ENT and pulmonary evaluations annually with sleep study and pulmonary function tests based on age and clinical manifestations; audiology examination annually throughout childhood and then every two years in adolescents and adults; ophthalmology examination every one to two years; echocardiogram and EKG every one to two years; abdominal MRI every two years or until organomegaly is improved on treatment; nerve conduction study every two years starting in school age or as needed; dental exams every six to 12 months.

Agents/circumstances to avoid: Individuals who have not had cervical fusion should not participate in activities that may result in cervical spine injury such as gymnastics. Cervical spine precautions must be taken during intubation for anesthesia.

Evaluation of relatives at risk: Testing of all at-risk sibs of any age is warranted to identify as early as possible those who would benefit from prompt initiation of enzyme replacement therapy and preventive measures.

Genetic counseling.

MPS VII is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a GUSB pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the GUSB pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.

Suggestive Findings

MPS VII should be suspected in a proband with any combination of the following clinical, radiographic, laboratory, and family history findings.

Clinical findings

• Fetal/neonatal presentation
  • Fetal demise / neonatal mortality
  • Nonimmune hydrops fetalis (Note: Presence of hydrops does not necessarily predict subsequent severity of disease in surviving neonates.)
  • Cholestatic jaundice
  • Hepatosplenomegaly
• Early childhood presentation
  • Musculoskeletal features (short neck, odontoid hypoplasia, disproportionate short-trunk short stature, pectus carinatum or excavatum, kyphosis, gibbus deformity, scoliosis, contractures, joint stiffness, genu valgum)
  • Developmental delay / intellectual disability with variable age of onset and severity that is typically evident by age two years
  • Characteristic craniofacial features (macrocephaly, coarse hair, coarse facies, corneal clouding, thick eyebrows, macroglossia, gingival hypertrophy, small and widely spaced teeth) (See Figure 1.)
  • Recurrent otitis media or respiratory infections
  • Snoring, enlarged tonsils and adenoids, obstructive sleep apnea
  • Hearing loss (sensorineural or conductive)
  • Prominent abdomen with hepatosplenomegaly
  • Hernias (umbilical and/or inguinal)
  • Thickening of mitral and/or aortic valve leaflets, valve insufficiency, valve stenosis, left ventricular hypertrophy

Figure 1.

Serial images of a male with mucopolysaccharidosis type VII at ages (A) 2.5 months, (B) six months, (C) one year, (D) three years, (E) five years, (F) six years, (G) seven years, (H) eight years, (I) nine years, and (J) 11 years, showing characteristic (more...)

Radiographic findings. Skeletal survey shows features of dysostosis multiplex including thickened cortical bone, abnormal J-shaped sella turcica, paddle- or oar-shaped ribs, short, thickened clavicles, platyspondyly and anterior beaking of the lower thoracic and lumbar vertebrae, rounded iliac wings, shallow acetabulae, coxa valga, genu valgum, proximal pointing of the metacarpals and metatarsals, and bullet-shaped phalanges.

Laboratory findings. Urine glycosaminoglycan (GAG) analysis demonstrates elevated concentrations of dermatan and chondroitin sulfate with increased levels of total GAGs.

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of MPS VII is established in a proband with increased levels of urinary GAGs, suggestive findings, and:

• Absent or reduced beta-glucuronidase enzyme activity in leukocytes, fibroblasts, or dried blood spots
  AND/OR
• Biallelic pathogenic (or likely pathogenic) variants in GUSB identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (2) Identification of biallelic GUSB variants of uncertain significance (or of one known GUSB pathogenic variant and one GUSB variant of uncertain significance) does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas comprehensive genomic testing does not (see Option 2).

Clinical Description

Individuals with mucopolysaccharidosis type VII (MPS VII) can present perinatally with early demise, nonimmune hydrops fetalis, cholestatic jaundice, and hepatosplenomegaly, or in early childhood with developmental delay and characteristic musculoskeletal and craniofacial features. To date, <200 individuals have been identified with biallelic pathogenic variants in GUSB. The following description of the phenotypic features associated with this condition is based on these reports.

Growth. Disproportionate short-trunk short stature occurs due to vertebral body dysplasia and spinal curvature and is often evident before age two years. Even in individuals with initially normal stature, growth velocity slows prematurely [Montaño et al 2016] so that final adult height is very likely to be two standard deviations below the mean. Those who survive nonimmune hydrops fetalis are generally of shorter stature than those who did not experience hydrops.

As adolescent weight tends to be above the 50th centile, the prevalence of overweight is higher especially for individuals who are not independently ambulatory. A study of intravenous enzyme replacement therapy initiated prior to age five years found improved growth velocity and z scores after 48 weeks of treatment, but long-term effects of therapy on final adult height and weight are not known [Lau et al 2022].

Musculoskeletal features. Dysostosis multiplex may be one of the first noted manifestations of MPS VII. In addition to disproportionate short-trunk short stature, spine manifestations include progressive scoliosis, kyphosis, lumbosacral gibbus, and spinal stenosis most commonly affecting the cervical region. Atlantoaxial instability results from odontoid hypoplasia. Glycosaminoglycan (GAG) storage in joint capsules, ligaments, and other connective tissue make restriction of joint mobility and contractures also very common. This is especially evident in the hip joint, where shallow acetabulae contribute to a high frequency of hip pain, difficulty walking, and osteoarthritis later in childhood and adolescence. Genu valgum and talipes equinovarus can develop. GAG storage can also cause carpal tunnel syndrome.

Neurologic. Spinal stenosis occurs as a result of GAG deposition in the dura and atlantooccipital instability. Spinal cord compression can develop as early as age one to two years and into adolescence. Young individuals or those with cognitive impairment may not report clinical symptoms of myelopathy, but hyperreflexia and ankle clonus can be found on physical exam. Similarly, they may not report symptoms of carpal tunnel syndrome. Hydrocephalus has been reported as a rare complication, but its exact prevalence is not known.

Developmental delay. A high frequency of conductive/mixed hearing loss contributes to speech delay, which is typically not recognized until after age 18 to 24 months. Gross motor and fine motor milestone acquisition is also delayed, a result of skeletal dysplasia compounded with accumulation of GAGs in the central nervous system. This may be evident in the first year of life as infants are delayed in sitting, crawling, standing, and walking. Enzyme replacement therapy may improve motor milestone acquisition, but very few individuals were assessed in the clinical trial [Lau et al 2022].

Intellectual disability. Most children with MPS VII have moderate-to-severe intellectual disability. Additionally, behavioral difficulties such as impulsivity, hyperactivity, insomnia, and hitting/kicking make this one of the most challenging aspects of MPS VII for caregivers [Montaño et al 2016]. As stored central nervous system GAGs are thought to be the etiology of neurocognitive deficits, intravenous enzyme replacement therapy is not expected to impact the intellect.

Craniofacial features. Macrocephaly, coarse hair, and gingival hypertrophy may be present in the neonatal period. Facial features coarsen with age, and affected individuals may develop macroglossia, corneal clouding, thick eyebrows, and thickened lips (see Figure 1). Dental problems include widely spaced teeth and poor enamel.

Respiratory complications. GAG storage in the upper airways and eustachian tubes results in recurrent bacterial acute otitis media as well as upper respiratory tract infections. Individuals often develop acute otitis media before they are able to clear prior middle ear effusions, resulting in chronic otitis and resultant conductive hearing loss. Macroglossia, in conjunction with adenoidal and tonsillar hypertrophy, contribute to upper airway obstructive disease and difficult airway management for anesthesiologists and otolaryngologists. Obstructive sleep apnea, lower respiratory tract infections, and restrictive lung disease also occur. As individuals get older, respiratory complications become one of the leading causes of morbidity and mortality [Montaño et al 2016]. In some instances, families and their care team opt for tracheostomy.

Gastrointestinal manifestations. Hepatosplenomegaly due to GAG storage is a common finding. Umbilical, inguinal, and hiatal hernias are also common. Unlike other MPS types, cholestatic jaundice is a well-known (if infrequent) manifestation of MPS VII and may be a consequence of fetal hepatic sinusoidal congestion and resultant liver dysfunction [Montaño et al 2016]. Feeding difficulties may necessitate thickeners and/or gastrostomy tube placement.

Cardiovascular complications. Accumulation of dermatan and chondroitin sulfate GAGs in heart valves results in progressive thickening of the heart valve leaflets. This is usually observed on echocardiography before age five years. Though initially valve thickening does not interfere with function, progressive disease results in defects of valve coaptation and subsequent valvular insufficiency and/or stenosis. Valvular disease affects all four heart valves but is most clinically significant in the mitral and aortic valves. Rarely, severity of valve dysfunction necessitates surgical valve replacement [Marek et al 2021]. Left ventricular hypertrophy and cardiomyopathy are also common findings. Life-threatening dysrhythmias, likely caused by subendocardial fibrosis, are a recurrent cause of death in individuals with MPS VII [Montaño et al 2016, Lew at al 2018]. Monitoring for abnormal cardiac rhythms should be conducted by experts in MPS during anesthesia.

Genotype-Phenotype Correlations

Genotype-phenotype correlations have been suggested, though sample size is small [Tomatsu et al 2009, Montaño et al 2016]. In general, GUSB nonsense variants and deletions tend to be associated with severe phenotypes. Individuals with residual enzyme activity >1.4% of normal enzyme activity have later disease onset and longer survival [Zielonka et al 2017].

Prevalence

MPS type VII is an ultrarare disorder with a global prevalence estimated to be <200 individuals [Harmatz et al 2018].

GUSB founder variants have been identified in the Mexican population, c.1244C>T (p.Pro415Leu) and c.[1244C>T;1222C>T] (p.[Pro415Leu;Pro408Ser]), the latter being two pathogenic variants occurring in cis. The c.1856C>T (p.Ala619Val) allele is a founder variant in the Japanese population [Tomatsu et al 2009]. The pathogenic variant c.526C>T (p.Leu176Phe) accounted for 96% of alleles in a Brazilian cohort, and almost all affected individuals were homozygous [Giugliani et al 2021]. To date, carrier frequency in these populations is unknown.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with MPS VII, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Treatment of Manifestations

Surveillance

Due to the broad clinical disease spectrum, surveillance should be tailored to the individual. To monitor existing manifestations, the individual's response to treatment, and the emergence of new manifestations, the evaluations summarized in Table 6 are recommended.

Agents/Circumstances to Avoid

Atlantoaxial instability can cause serious neurologic injury. Individuals who have not had cervical fusion should not participate in activities that may result in cervical spine injury such as gymnastics. Cervical spine precautions must be taken during intubation for anesthesia.

Evaluation of Relatives at Risk

Testing of all at-risk sibs of any age is warranted to identify as early as possible those who would benefit from prompt initiation of enzyme replacement therapy and preventive measures.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Mode of Inheritance

Mucopolysaccharidosis type VII (MPS VII) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

• The parents of an affected child are presumed to be heterozygous for a GUSB pathogenic variant.
• Molecular genetic testing is recommended for the parents of the proband to confirm that both parents are heterozygous for a GUSB pathogenic variant and to allow reliable recurrence risk assessment.
• If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a de novo event in the proband or as a postzygotic de novo event in a mosaic parent [Jónsson et al 2017]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:
  • A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;
  • Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.
• Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

• If both parents are known to be heterozygous for a GUSB pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
• Based on limited case reports, affected sibs appear to manifest similar disease courses [Van Dorpe et al 1996, Montaño et al 2016].
• Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Offspring of a proband. The offspring of an individual with MPS VII are obligate heterozygotes (carriers) for a pathogenic variant in GUSB.

Other family members. Each sib of the proband's parents is at a 50% risk of being a carrier of a GUSB pathogenic variant.

Carrier Detection

Molecular genetic testing. Molecular genetic carrier testing for at-risk relatives requires prior identification of the GUSB pathogenic variants in the family.

Carriers usually have low-normal or slightly deficient beta-glucuronidase enzyme activity; thus, molecular genetic testing is required to determine carrier status.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

• The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.
• Carrier testing should be considered for the reproductive partners of known carriers and for the reproductive partners of individuals affected with MPS VII, particularly if both partners are of the same ancestral background. Founder variants have been identified in the Mexican, Japanese, and Brazilian populations (see Table 7).

DNA banking. Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see Huang et al [2022].

Prenatal Testing and Preimplantation Genetic Testing

Molecular genetic testing. Once both GUSB pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing for MPS VII are possible.

Biochemical testing. Beta-glucuronidase enzyme analysis can be performed on cultured chorionic villus cells or amniocytes.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.

Molecular Pathogenesis

Mucopolysaccharidosis type VII is caused by deficiency of the lysosomal enzyme beta-glucuronidase, which is involved in the degradation of chondroitin sulfate, dermatan sulfate, and heparan sulfate. The partially degraded glycosaminoglycans accumulate in the lysosomes of many tissues, leading to cell and organ dysfunction.

Mechanism of disease causation. Loss-of-function variants result in absent or decreased enzyme activity.

GUSB-specific laboratory technical considerations. Pseudodeficiency alleles are non-pathogenic variants that cause decreased enzyme activity in vitro but do not result in clinical disease. At least one pseudodeficiency allele has been reported for GUSB, c.454G>A (p.Asp152Asn) [Vervoort et al 1995]. In addition, several pseudogenes exist [Tomatsu et al 2009].

Acknowledgments

The authors wish to thank the individuals with mucopolysaccharidosis type VII (MPS VII) and their families along with international research efforts that continue to improve our understanding of MPS VII.

Revision History

• 4 January 2024 (sw) Review posted live
• 7 July 2023 (as) Original submission

Literature Cited

• Giugliani R, Barth AL, Dumas MRC, da Silva Franco JF, de Rosso Giuliani L, Grangeiro CHP, Horovitz DDG, Kim CA, de Araújo Leão EKE, de Medeiros PFV, Miguel DSCG, Moreira MESA, Dos Santos HMGP, da Silva LCS, da Silva LR, de Souza IN, Nalin T, Garcia D. Mucopolysaccharidosis VII in Brazil: natural history and clinical findings. Orphanet J Rare Dis. 2021;16:238. [PMC free article: PMC8141134] [PubMed: 34022924]
• Harmatz P, Whitley CB, Wang RY, Bauer M, Song W, Haller C, Kakkis E. A novel blind start study design to investigate vestronidase alfa for mucopolysaccharidosis VII, an ultra-rare genetic disease. Mol Genet Metab. 2018;123:488-94. [PubMed: 29478819]
• Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. J Community Genet. 2022;13:389-97. [PMC free article: PMC9314484] [PubMed: 35834113]
• Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature. 2017;549:519-22. [PubMed: 28959963]
• Lau HA, Viskochil D, Tanpaiboon P, Lopez AG, Martins E, Taylor J, Malkus B, Zhang L, Jurecka A, Marsden D. Long-term efficacy and safety of vestronidase alfa enzyme replacement therapy in pediatric subjects < 5 years with mucopolysaccharidosis VII. Mol Genet Metab. 2022;136:28-37. [PubMed: 35331634]
• Lew V, Pena L, Edwards R, Wang RY. Cardiovascular histopathology of a 11-year old with mucopolysaccharidosis VII demonstrates fibrosis, macrophage infiltration, and arterial luminal stenosis. JIMD Rep. 2018;39:31-7. [PMC free article: PMC5953895] [PubMed: 28702876]
• Marek J, Kuchynka P, Mikulenka V, Palecek T, Sikora J, Hulkova H, Lambert L, Linkova H, Zemanek D, Tesarova M, Linhart A, Zeman J, Magner M. Combined valve replacement and aortocoronary bypass in an adult mucopolysaccharidosis type VII patient. Cardiovasc Pathol. 2021;50:107297. [PubMed: 33045360]
• Montaño AM, Lock-Hock N, Steiner RD, Graham BH, Szlago M, Greenstein R, Pineda M, Gonzalez-Meneses A, Çoker M, Bartholomew D, Sands MS, Wang R, Giugliani R, Macaya A, Pastores G, Ketko AK, Ezgü F, Tanaka A, Arash L, Beck M, Falk RE, Bhattacharya K, Franco J, White KK, Mitchell GA, Cimbalistiene L, Holtz M, Sly WS. Clinical course of Sly syndrome (mucopolysaccharidosis type VII). J Med Genet. 2016;53:403-18. [PMC free article: PMC4893087] [PubMed: 26908836]
• Morrison A, Oussoren E, Friedel T, Cruz J, Yilmaz N. Pathway to diagnosis and burden of illness in mucopolysaccharidosis type VII - a European caregiver survey. Orphanet J Rare Dis. 2019;14:254. [PMC free article: PMC6854616] [PubMed: 31727109]
• Poswar FO, Henriques Nehm J, Kubaski F, Poletto E, Giugliani R. Diagnosis and emerging treatment strategies for mucopolysaccharidosis VII (Sly syndrome). Ther Clin Risk Manag. 2022;18:1143-55. [PMC free article: PMC9791935] [PubMed: 36578769]
• Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-24. [PMC free article: PMC4544753] [PubMed: 25741868]
• Sparks TN, Lianoglou BR, Adami RR, Pluym ID, Holliman K, Duffy J, Downum SL, Patel S, Faubel A, Boe NM, Field NT, Murphy A, Laurent LC, Jolley J, Uy C, Slavotinek AM, Devine P, Hodoglugil U, Van Ziffle J, Sanders SJ, MacKenzie TC, Norton ME; University of California Fetal–Maternal Consortium; University of California, San Francisco Center for Maternal–Fetal Precision Medicine. Exome sequencing for prenatal diagnosis in nonimmune hydrops fetalis. N Engl J Med. 2020;383:1746-56. [PMC free article: PMC7650529] [PubMed: 33027564]
• Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. Hum Genet. 2020;139:1197-207. [PMC free article: PMC7497289] [PubMed: 32596782]
• Tomatsu S, Montaño AM, Dung VC, Grubb JH, Sly WS. Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly syndrome). Hum Mutat. 2009;30:511-9. [PMC free article: PMC3048808] [PubMed: 19224584]
• Van Dorpe J, Moerman P, Pecceu A, Van den Steen P, Fryns JP. Non-immune hydrops fetalis caused by beta-glucuronidase deficiency (mucopolysaccharidosis VII). Study of a family with 3 affected siblings. Genet Couns. 1996;7:105-12. [PubMed: 8831129]
• Vervoort R, Islam MR, Sly W, Chabas A, Wevers R, de Jong J, Liebaers I, Lissens W. A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene. Am J Hum Genet. 1995;57:798-804. [PMC free article: PMC1801516] [PubMed: 7573038]
• Wang RY, da Silva Franco JF, López-Valdez J, Martins E, Sutton VR, Whitley CB, Zhang L, Cimms T, Marsden D, Jurecka A, Harmatz P. The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII. Mol Genet Metab. 2020;129:219-27. [PubMed: 32063397]
• Zielonka M, Garbade SF, Kölker S, Hoffmann GF, Ries M. Quantitative clinical characteristics of 53 patients with MPS VII: a cross-sectional analysis. Genet Med. 2017;19:983-8. [PubMed: 28383542]