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Mutation type profile and Exon distribution of MPS III. (A) Mutation type profile in patients with MPS IIIA and IIIB. (B,C) Exon distribution of the SGSH and NAGLU mutations in this study. Most were missense mutations (92.3% in SGSH mutations, 88.9% in NAGLU mutations). J. Pers. Med. 2022, 12, x FOR PEER REVIEW 10 of 15
Source publication
Background:
Mucopolysaccharidosis type III (MPS III) is an autosomal recessive lysosomal storage disorder characterised by progressive neurocognitive deterioration. MPS III subtypes are clinically indistinguishable, with a wide range of symptoms and variable severity. The natural history of this disorder within an Asian population has not yet been...
Citations
... Previous studies have reported only five cases of MPS IIIC in Asia, which includes two siblings in a Korean family, two cases from China, one case from Japan, confirming its ultra-rare occurrence in Asia (Kim et al. 2022;Kong et al. 2020a, b;Kurihara et al. 1996;Lin et al. 2018). ...
... However, they occurred in trans in only one patient in our cohort. This combination has been identified in the Korean MPS IIIC sibling (Kim et al. 2022). ...
Background
Mucopolysaccharidosis type IIIC (MPS IIIC; Sanfilippo syndrome C) is a rare lysosomal storage disease caused by mutations in the heparan-α-glucosaminide N-acetyltransferase (HGSNAT) gene, resulting in the accumulation of heparan sulfate. MPS IIIC is characterized by severe neuropsychiatric symptoms and mild somatic symptoms.
Methods
Our study analyzed the clinical presentation and biochemical characteristics of ten Chinese MPS IIIC patients from eight families. Whole exome sequencing was applied to identify the variants in HGSNAT gene. In one patient with only one mutant allele identified firstly, whole genome sequencing was applied. The pathogenic effect of novel variants was evaluated in silico.
Results
The mean age at the onset of clinical symptoms was 4.2 ± 2.5 years old, and the mean age of diagnosis was 7.6 ± 4.5 years old, indicating a delay of diagnosis. The most common onset symptoms were speech deterioration, and the most frequent presenting symptoms are speech deterioration, mental deterioration, hyperactivity and hepatomegaly, sequentially. All mutant alleles of 10 patients have been identified. There were eleven different HGSNAT variants, and the most common one was a previously reported variant c.493 + 1G > A. There were six novel variants, p.R124T, p.G290A, p.G426E, c.743 + 101_743 + 102delTT, c.851 + 171T > A and p.V582Yfs*18 in our cohort. Extraordinarily, two deep intron variants were identified in our cohort, with the variant c.851 + 171T > A identified by whole genome sequencing.
Conclusion
This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients, which would assist in the early diagnosis and genetic counselling of MPS IIIC.
... В качестве наиболее раннего симптома отмечена задержка речи (88,2%), задержка моторики (76,5%), общее отставание (64,7%) и гиперактивность (41,2%). В исследовании A. Meyer et al., включавшем 85 пациентов с МПС IIIA и IIID из Испании и Турции, первые симптомы заболевания дебютировали в 7-месячном возрасте, регрессия речевой, двигательной и когнитивной функций проявилась к 3,3 года с потерей всех трех оцениваемых способностей к 12,5 года [12][13][14]. ...
Introduction . Mucopolysaccharidosis type III (Sanfilippo syndrome) is a rare multi-stem disease caused by the accumulation of glycosaminoglycans (GAG) in the cells of various organs, leading to a violation of their function, specific phentopic signs and progressive neurocognitive disorders. Neurologic manifestations are leading in the clinical picture of the disease, as by the time of manifestation, and by severity. In most patients, in the first and even second years of life, children have normal development or indistinctly pronounced deviations. In the absence of substitute enzyme therapy for this type of MPS, a severe delay in intellectual and speech development develops rapidly, recurrent respiratory episodes in the form of pneumonia and bronchial obstruction are observed, the child is disabled early. Polymorphism and non-specificity of clinical manifestations, lack of alertness of doctors to orphan diseases are a common cause of late diagnosis of MPS. The article presents an overview of data on the prevalence, genetic and phenotypic variants of type III mucopolysaccharidosis, features of patient management and presentation of clinical observation of a child with this pathology.
Clinical observation . We present our own prolonged clinical observation of a type III MPS case in a patient who has been under our supervision for 12 years. The diagnosis was established and confirmed at the age of three years. The disease was manifested by neuropsychiatric regression and systemic somatic manifestations. Motor deficits, cognitive impairments with the development of dementia and recurrent aspiration syndrome progressed in the dynamics of the child.
Conclusions . The classical clinical picture of type III MPS is distinguished by the aggressive development of cognitive and motor disorders at 2–3 years of life, characteristic phenotypic and somatic manifestations of the disease. This case demonstrates the multiplicity of problems and the need for interaction between doctors of various specialties.
