Clinical, biochemical, and molecular characterization of mucopolysaccharidosis type III in 34 Egyptian patients

Abstract

Mucopolysaccharidosis type III (MPS III) is a rare autosomal recessive lysosomal storage disorder characterized by progressive neurocognitive deterioration. There are four MPS III subtypes (A, B, C, and D) that are clinically indistinguishable with variable rates of progression. A retrospective analysis was carried out on 34 patients with MPS III types at Cairo University Children's Hospital. We described the clinical, biochemical, and molecular spectrum of MPS III patients. Of 34 patients, 22 patients had MPS IIIB, 7/34 had MPS IIIC, 4/34 had MPS IIIA, and only 1 had MPS IIID. All patients presented with developmental delay/intellectual disability, and speech delay. Ataxia was reported in a patient with MPS IIIC, and cerebellar atrophy in a patient with MPS IIIA. We reported 25 variants in the 4 MPS III genes, 11 of which were not previously reported. This is the first study to analyze the clinical and genetic spectrum of MPS III patients in Egypt. This study explores the genetic map of MPS III in the Egyptian population. It will pave the way for a national registry for rare diseases in Egypt, a country with a high rate of consanguineous marriage and consequently a high rate of autosomal recessive disorders.

Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation

“…The p.L146P is a missense mutation previously described only in one Italian patient, drastically changing the protein structure, and leading to a severe phenotype [ 33 ]. Neurodegeneration in mucopolysaccharidosis III has been demonstrated independently of the specific genetic mutation [ 34 – 36 ], being the result of axonal dystrophy with an accumulation of ubiquitin-positive lesions containing phosphorylated-tau, wildtype α-synuclein, APP and β-amyloid, as shown by clinical and preclinical evidence [ 37 – 39 ]. However, mice carrying heterozygous p.D31N mutation in SGSH did not show an increased presence of brain pathology or neurodegeneration compared to controls, nor a significant accumulation of heparan sulfate despite a 50% reduction in SGSH levels.…”