Compound heterozygous missense mutations in a Chinese mucopolysaccharidosis type VI patient: a case report

Abstract Background Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive inherited disease caused by mutations in the arylsulfatase B (ARSB) gene. MPS VI is a multisystemic disease resulting from a deficiency in arylsulfatase B causing an accumulation of glycosaminoglycans in the tissues and organs of the body. In this report, we present the case of a 16-year-old Chinese male who presented with vision loss caused by corneal opacity. MPS VI was confirmed by genetic diagnosis. Case presentation A 16-year-old Chinese male presented with a one-year history of binocular vision loss. The best-corrected visual acuity was 0.25 in the right eye and 0.5 in the left eye. Although slit-lamp examination revealed corneal opacification in both eyes, the ocular examinations of his parents were normal. At the same time, the patient presented with kyphotic deformity, short stature, joint and skeletal malformation, thick lips, long fingers, and coarse facial features. Genetic assessments revealed that ARSB was the causative gene. Compound heterozygous missense mutations were found in the ARSB gene, namely c.1325G > A (p. Thr442Met) (M1) and c.1197G > C (p. Phe399Leu) (M2). Genetic diagnosis confirmed that the patient had MPS VI. Conclusions This paper reports a case of MPS VI confirmed by genetic diagnosis. MPS VI is a multisystem metabolic disease, with corneal opacity as a concomitant ocular symptom. As it is difficult for ophthalmologists to definitively diagnose MPS VI, genetic testing is useful for disease confirmation.

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Early Diagnosis and Results of Enzyme Replacement Therapy in the Patient with Mucopolysaccharidosis Type VI: Clinical Case

Вопросы современной педиатрии ◽

10.15690/vsp.v20i6s.2369 ◽

2021 ◽

Author(s):

Dmitry V. Ivanov ◽

Anna I. Ostrun ◽

Vladimir M. Kenis ◽

Tatiana V. Markova ◽

Ekaterina Yu. Zakharova

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Clinical Case ◽

Mucopolysaccharidosis Type ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Mucopolysaccharidosis Type Vi ◽

Mps Vi ◽

Arylsulfatase B ◽

Arsb Gene

Background. Mucopolysaccharidosis type VI (MPS VI, Maroteaux–Lamy syndrome) is rare autosomal-recessive multisystem disease, one of the group of lysosomal storage diseases. The MPS VI pathogenesis is determined by arylsulfatase B enzyme deficiency caused by mutations in the ARSB gene. There are only few published clinical examples of this disease that covers the results of early enzyme replacement therapy (ERT) onset.Clinical case description. The child was suspected to have lysosomal storage disease at the age of 1.5 months, it was based on microscopic analysis of blood smears: Alder abnormality was revealed (granulations and red-violet inclusions in neutrophils, monocytes, lymphocytes cytoplasm). The diagnosis was confirmed at the age of 3 months: increased glycosaminoglycans (GAGs) concentration in the urine, arylsulfatase B activity decrease in dried blood spots, and pathogenic variant c.943C>T (p. R315X) in the ARSB gene in homozygous state were revealed. ERT with galsulfase was started at the age of 7 months. There was decrease in excretion of GAGs in urine to normal level after 9 and 15 months of therapy. Normal growth and body proportions for the patient’s age were determined 3 years after continuous ERT. However, there was progression of multiple dysostosis and joint stiffness, as well as eyes lesion.Conclusion. Early ERT onset cannot completely stop MPS VI progression but it allows to reduce the severity of several symptoms and improves patient’s quality of life.

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Hydrocephalus in mucopolysaccharidosis Type VI successfully treated with endoscopic third ventriculostomy

Journal of Neurosurgery Pediatrics ◽

10.3171/2012.11.peds11419 ◽

2013 ◽

Vol 11 (3) ◽

pp. 327-330 ◽

Cited By ~ 7

Author(s):

Ângelo Raimundo da Silva Neto ◽

Gervina Brady Moreira Holanda ◽

Maria Cláudia Saldanha Farias ◽

Gladstone Santos da Costa ◽

Hougelle Simplício Gomes Pereira

Keyword(s):

Carpal Tunnel Syndrome ◽

Fourth Ventricle ◽

Endoscopic Third Ventriculostomy ◽

Third Ventriculostomy ◽

Communicating Hydrocephalus ◽

Mucopolysaccharidosis Type ◽

Mucopolysaccharidosis Type Vi ◽

Mps Vi ◽

Arylsulfatase B ◽

Tunnel Syndrome

Mucopolysaccharidosis (MPS) Type VI, or Maroteaux-Lamy syndrome, is characterized by a deficiency of the enzyme arylsulfatase B (ASB). In patients with this disorder, craniocervical compression, carpal tunnel syndrome, and communicating hydrocephalus are common. Traditionally, hydrocephalus occurring in patients with MPS VI has been treated with shunt placements. Considering obstruction of the outlets from the fourth ventricle at the craniocervical transition, the authors decided to treat a female patient with MPS VI via endoscopic third ventriculostomy. She was 12 years old and had refractory headaches. This seems to be the first reported instance of the neuroendoscopic treatment of hydrocephalus in a patient with MPS VI. The pathophysiology is briefly discussed.

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Thrombocytopenia associated with galsulfase treatment

Human & Experimental Toxicology ◽

10.1177/0960327110379023 ◽

2010 ◽

Vol 30 (7) ◽

pp. 768-771 ◽

Cited By ~ 4

Author(s):

Murat Doğan ◽

Yasar Cesur ◽

Erdal Peker ◽

Ahmet F Oner ◽

Sekibe Zehra Dogan

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Lysosomal Storage Disorder ◽

Mucopolysaccharidosis Type ◽

Lysosomal Storage ◽

Cultured Fibroblasts ◽

Enzyme Replacement ◽

Mucopolysaccharidosis Type Vi ◽

Mps Vi ◽

Arylsulfatase B

Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder that results from a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase or arylsulfatase B (ASB). It is a relatively rare disorder, with an estimated incidence of 1 in 248,000 to 1 in 300,000. The diagnosis is made on the basis of findings of elevated urine glycosaminoglycans and a deficiency of ASB activity in leukocytes or cultured fibroblasts. In treatment of MPS VI, enzyme replacement therapy (galsulfase; human recombinant ASB enzyme) became available. Infusions of galsulfase were generally well tolerated. But in some patients, infusion-associated reactions including rash, urticaria, headache, hypotension, nausea, and vomiting were documented and were managed successfully by interrupting or slowing the rate of infusion and/or by the administration of antihistamines, antipyretics, corticosteroids, or oxygen. Here, we report a case with MPS VI who developed thrombocytopenia after third dose of therapy. To the best of our knowledge, this is the first report about thrombocytopenia associated with galsulfase therapy in the literature. Additionally, with this report, we want to share our approach for this case.

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Mucopolysaccharidosis type VI enzyme replacement therapy initiated in adulthood: Findings from the MPS VI clinical surveillance program

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2017.12.141 ◽

2018 ◽

Vol 123 (2) ◽

pp. S59

Author(s):

Paul Harmatz ◽

Christina Lampe ◽

Rossella Parini ◽

Reena Sharma ◽

Elisa Leão Teles ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Surveillance Program ◽

Mucopolysaccharidosis Type ◽

Enzyme Replacement ◽

Mucopolysaccharidosis Type Vi ◽

Mps Vi ◽

Clinical Surveillance

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Overexpression of N-acetylgalactosamine-4-sulphatase induces a multiple sulphatase deficiency in mucopolysaccharidosis-type-VI fibroblasts

Biochemical Journal ◽

10.1042/bj2940657 ◽

1993 ◽

Vol 294 (3) ◽

pp. 657-662 ◽

Cited By ~ 19

Author(s):

D S Anson ◽

V Muller ◽

J Bielicki ◽

G S Harper ◽

J J Hopwood

Keyword(s):

Practical Importance ◽

High Titre ◽

Skin Fibroblasts ◽

Mucopolysaccharidosis Type ◽

Subcellular Compartment ◽

Mucopolysaccharidosis Type Vi ◽

Steroid Sulphatase ◽

Mps Vi ◽

Genetically Determined ◽

Processing Mechanism

High-titre stocks of an amphotropic retrovirus, constructed so as to express a full-length cDNA encoding the human lysosomal enzyme N-acetylgalactosamine-4-sulphatase (4-sulphatase) from the cytomegalovirus immediate early promoter, were used to infect skin fibroblasts from a clinically severe mucopolysaccharidosis type VI (MPS VI) patient. The infected MPS VI cells showed correction of the enzymic defect with the enzyme being expressed at high levels and in the correct subcellular compartment. Surprisingly this did not result in correction of glycosaminoglycan turnover as measured by accumulation of 35S in metabolically labelled cells. We demonstrate that this is apparently caused by an induced reduction of the activities of other lysosomal sulphatases, presumably due to competition for a sulphatase-specific processing mechanism by the over-expressed 4-sulphatase. The level of steroid sulphatase, which is a microsomal sulphatase, was also reduced. Infection of skin fibroblasts from a second, clinically mildly affected, MPS VI patient with the same virus also resulted in no significant change in the level of glycosaminoglycan storage. However, in this case the cause of the observed phenomenon was less clear. These results are of obvious practical importance when considering gene therapy for a sulphatase deficiency such as MPS VI and also provide possible new avenues for exploration of the processes involved in sulphatase synthesis and genetically determined multiple sulphatase deficiency.

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Case of a Mongolian child with extensive Mongolian spots in mucopolysaccharidosis type VI: Identification of a novel mutation in the arylsulfatase B gene

The Journal of Dermatology ◽

10.1111/1346-8138.12237 ◽

2013 ◽

Vol 40 (9) ◽

pp. 758-759

Author(s):

Ken Okamura ◽

Batmunkh Munkhbat ◽

Batbaatar Batchimeg ◽

Gen Tamiya ◽

Yutaka Hozumi ◽

...

Keyword(s):

Novel Mutation ◽

Mucopolysaccharidosis Type ◽

Mucopolysaccharidosis Type Vi ◽

Arylsulfatase B

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Arylsulfatase B* has demonstrated positive phase-III results in patients with mucopolysaccharidosis type VI.

Inpharma Weekly ◽

10.2165/00128413-200414410-00013 ◽

2004 ◽

Vol &NA; (1441) ◽

pp. 7

Author(s):

&NA;

Keyword(s):

Phase Iii ◽

Positive Phase ◽

Mucopolysaccharidosis Type ◽

Mucopolysaccharidosis Type Vi ◽

Arylsulfatase B

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Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) in the pre-Columbian culture of Colombia

Colombia Medica ◽

10.25100/cm.v45i2.1441 ◽

2014 ◽

pp. 85-88 ◽

Cited By ~ 3

Author(s):

Harry Pachajoa ◽

Carlos Armando Rodriguez

Keyword(s):

Lysosomal Storage Disorder ◽

Autosomal Recessive ◽

Pacific Coast ◽

Facial Dysmorphism ◽

Mucopolysaccharidosis Type ◽

Lysosomal Storage ◽

Dysostosis Multiplex ◽

Mucopolysaccharidosis Type Vi ◽

Corneal Clouding ◽

Arylsulfatase B

Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism, with intelligence usually normal. We present evidence of the possible existence of Maroteaux Lamy syndrome in pre-Columbian pottery 2000 years ago, in the Colombo Ecuadorian Pacific coast of the Tumaco-Tolita culture.

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