Mucopolysaccharidosis-Plus Syndrome

Abstract

Previously, we reported a novel disease of impaired glycosaminoglycans (GAGs) metabolism without deficiency of known lysosomal enzymes—mucopolysaccharidosis-plus syndrome (MPSPS). MPSPS, whose pathophysiology is not elucidated, is an autosomal recessive multisystem disorder caused by a specific mutation p.R498W in the VPS33A gene. VPS33A functions in endocytic and autophagic pathways, but p.R498W mutation did not affect both of these pathways in the patient’s skin fibroblast. Nineteen patients with MPSPS have been identified: seventeen patients were found among the Yakut population (Russia) and two patients from Turkey. Clinical features of MPSPS patients are similar to conventional mucopolysaccharidoses (MPS). In addition to typical symptoms for conventional MPS, MPSPS patients developed other features such as congenital heart defects, renal and hematopoietic disorders. Diagnosis generally requires evidence of clinical picture similar to MPS and molecular genetic testing. Disease is very severe, prognosis is unfavorable and most of patients died at age of 10–20 months. Currently there is no specific therapy for this disease and clinical management is limited to supportive and symptomatic treatment.

Mucopolysaccharidosis-Plus Syndrome, a Rapidly Progressive Disease: Favorable Impact of a Very Prolonged Steroid Treatment on the Clinical Course in a Child

“…Mucopolysaccharidosis-plus syndrome (MPS-PS) is an autosomal recessive disorder recently described within LSD. The only mutation reported so far is the c.1492C>T (p.R498W) missense mutation in the VPS33A gene [ 7 , 8 , 9 , 10 ].…”

“…Twenty-four patients have been described to date: twenty-two patients among the Yakut population [ 7 , 9 ] and two from Turkey [ 8 ]. All patients from Yakutia (northeast Siberia, the Sakha Republic in the Russian Federation) were born to nonconsanguineous healthy parents.…”

“…All patients from Yakutia (northeast Siberia, the Sakha Republic in the Russian Federation) were born to nonconsanguineous healthy parents. The incidence rate of MPS-PS among Yakuts is predicted as 1 per 12–15,000 births [ 7 ], while allele frequency has been found to be 1 in 110 in a random healthy population [ 8 ]. In fact, the Yakut population is characterized by a high degree of genetic homogeneity due to geographical isolation and low migration.…”

Editorial: Molecular Aspects of Mucopolysaccharidoses

“…Mucopolysaccharidoses (MPS) are a group of 13 diseases (see Table 1 for details) belonging to lysosomal storage disorders (LSD) that occur with cumulative frequencies of all their types of about 1 per 40,000—50,000 live births ( Çelik et al, 2021 ). Out of these 13 types of MPS, 11 are known since many years, while 2 types were discovered recently, MPS X ( Verheyen et al, 2022 ) and MPS-plus-syndrome (MPSPS) ( Vasilev et al, 2020 ). All MPS diseases are caused by mutations in genes coding for enzymes involved in metabolism (usually catabolism) of glycosaminoglycans (GAGs) (formerly called mucopolysaccharides).…”

“… a Summary on mucopolysaccharidoses I-IX was presented by Tomatsu et al (2018) , MPS X has been discovered recently by Verheyen et al (2022) , and MPS-plus-syndrome (MPSPS) was characterized recently by Vasilev et al (2020) (note that an MPS plus-like syndrome has been described in patients with mutations in the VPS16 gene, coding for vacuolar protein sorting protein 16; Yıldız et al, 2021 ). …”