Sanfilippo syndrome: Overall review

Abstract

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of the four enzymes involved in the catabolism of glycosaminoglycan heparan sulfate. It is characterized by progressive cognitive decline and severe hyperactivity, with relatively mild somatic features. This review focuses on clinical features, diagnosis, treatment, and follow-up of MPS III, and provides information about supplementary tests and differential diagnosis. Given that few reviews of MPS III have been published, several studies were compiled to establish diagnostic recommendations. Quantitative urinary glycosaminoglycan analysis is strongly recommended, and measurement of disaccharides, heparin cofactor II-thrombin complex and gangliosides is also used. Enzyme activity of the different enzymes in blood serum, leukocytes or fibroblasts, and mutational analysis for SGSH, NAGLU, HGSNAT or GNS genes are required to confirm diagnosis and differentiate four subtypes of MPS III. Although there is no global consensus for treatment, enzyme replacement therapy and gene therapy can provide appropriate results. In this regard, recent publications on treatment and follow-up are discussed.

A novel frameshift deletion in NAGLU causing sanfilipo type III‐B in an Indian family

“…MPS disorders are caused by the deficiency of a specific lysosomal enzyme which is required for the GAG degradation. Sanfilipo syndrome (MPS III), results from deficiency of different lysosomal enzymes involved in degradation of heparan sulfate . MPS III includes four subtypes on the basis of the different lysosomal enzymes involved in the degradation of GAGs .…”

“…Mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders which is characterized by abnormal accumulation of partially degraded glycosaminoglycan (GAGs) fragments in urine, blood, and cerebral spinal fluid. 1,2 MPS disorders are caused by the deficiency of a specific lysosomal enzyme which is required for the GAG degradation. Sanfilipo syndrome (MPS III), results from deficiency of different lysosomal enzymes involved in degradation of heparan sulfate.…”

“…Sanfilipo syndrome (MPS III), results from deficiency of different lysosomal enzymes involved in degradation of heparan sulfate. 1,2 MPS III includes four subtypes on the basis of the different lysosomal enzymes involved in the degradation of GAGs. [2][3][4] The four enzymes involved namely sulfamidase (MPS Type III-A), α-N-acetylglucosaminidase (MPS Type III-B), acetyl-CoA:a-glucosaminide N-acetyltransferase (MPS Type III-C), and N-acetylglucosamine-6-sulfate sulfatase (MPS Type III-D) are responsible for the stepwise degradation of heparan sulfate ( Figure 1A).…”

“…[2][3][4] The four enzymes involved namely sulfamidase (MPS Type III-A), α-N-acetylglucosaminidase (MPS Type III-B), acetyl-CoA:a-glucosaminide N-acetyltransferase (MPS Type III-C), and N-acetylglucosamine-6-sulfate sulfatase (MPS Type III-D) are responsible for the stepwise degradation of heparan sulfate ( Figure 1A). 2,4…”

Evaluation of Demographic and Clinical Characteristics of Patients with Mucopolysaccharidosis

“…In MPS patients, clinical manifestations including cardiovascular diseases (common and early finding), obstructive type respiratory diseases, auditory impairment, visual problems (corneal clouding, glaucoma, retinal degeneration), and musculoskeletal diseases (short stature, joint stiffness or hyperlaxity, peripheral nerve entrapment neuropathy), where multiple organs are involved, can be observed (1,4). In patients who are suspected of having MPS based on clinical findings, firstly urinary GAG measurement is performed followed by specific lysosomal enzyme activity in leukocytes for definitive diagnosis (5).…”