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Orphanet Journal of Rare Diseases May 2024To investigate the peripheral nervous system involvement in sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials...
BACKGROUND
To investigate the peripheral nervous system involvement in sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system.
METHODS
The clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients.
RESULTS
Six patients (M/F: 2:4) were recruited. In addition to the classical presentation, intermittent painful paresthesia was noted in four patients, and three of whom reported it as the earliest symptom. In the NCSs, one patient had reduced compound muscle action potential amplitudes in the right ulnar nerve, while another patient had prolonged distal motor latency in the bilateral tibial and peroneal nerves. Prolonged F-wave latency (83.3%), repeater F-waves (50%), and neurogenic polyphasic waves in EMG (in 2 out of 3 examined patients) were also noted. Interestingly, a very late response was noted in the F-wave study of all patients, probably indicating lesions involving the proximal peripheral nerve or spinal cord.
CONCLUSION
In addition to the central nervous system, the peripheral nervous system is also involved in sialidosis, with corresponding clinical symptoms. Further study on these phenomena is indicated.
Topics: Humans; Male; Female; Adult; Mucolipidoses; Electromyography; Neural Conduction; Young Adult; Peripheral Nerves; Adolescent; Peripheral Nervous System; Evoked Potentials, Somatosensory; Middle Aged; Child
PubMed: 38790028
DOI: 10.1186/s13023-024-03216-8 -
Annals of Medicine and Surgery (2012) Apr 2024Sialidosis is a rare variety of lysosomal storage disease that results in intracellular accumulation of sialic acid containing compounds. The authors report the first...
BACKGROUND
Sialidosis is a rare variety of lysosomal storage disease that results in intracellular accumulation of sialic acid containing compounds. The authors report the first case of type II sialidosis, juvenile subtype in a 30-month-old male child from Nepal.
CASE PRESENTATION
Progressive hearing loss with coarse facies, hepatomegaly, kyphoscoliosis, dysostosis multiplex were the major features in a 30-month-old child born to healthy non-consanguineous parents. With the suspicion of lysosomal storage disease, urinary oligosaccharides were tested and were positive. Whole-exome sequencing revealed a mutation in the neuraminidase gene (NEU1) and established the diagnosis of sialidosis.
CLINICAL DISCUSSION
Sialidosis is a rare autosomal recessive type of lysosomal storage disease resulting due to mutation of the neuraminidase gene leading to intracellular accumulation of sialic acid compounds. Based on the presence of visual symptoms, sialidosis is classified into type I and II varieties. Our case is of type II juvenile sialidosis.
CONCLUSION
Despite rare, sialidosis is a life-threatening, and disabling disease. Exploring targeted therapy is the utmost to treat this condition.
PubMed: 38576973
DOI: 10.1097/MS9.0000000000001768 -
Journal of Children's Orthopaedics Apr 2024Literature regarding total hip arthroplasty for pediatric hip diseases is scarce. This review aims to portray the various orthopedic conditions of childhood that can... (Review)
Review
PURPOSE
Literature regarding total hip arthroplasty for pediatric hip diseases is scarce. This review aims to portray the various orthopedic conditions of childhood that can lead to significant impairment of the hip joint and, ultimately, to total hip arthroplasty in adolescence and adulthood.
METHODS
In total, 61 out of 3666 articles were selected according to (1) the diagnosis of one of the 12 pediatric hip pathologies (Legg-Perthes-Calvé disease, developmental dysplasia of the hip, slipped capital femoral epiphysis, neuromuscular hip dysplasia, post-traumatic avascular necrosis of the proximal femur, juvenile rheumatoid arthritis, achondroplasia, spondyloepiphyseal dysplasia, mucopolysaccharidosis, mucolipidosis, hip infections, and tumors) that required total hip arthroplasty; (2) minimum follow-up of 16 months; (3) assessed outcome with a clinical or radiologic score; (4) Methodological Items for Non-Randomized Studies quality score of 9 or higher. The following information for each pathology was retrieved: mean age at total hip arthroplasty, reason for total hip arthroplasty, type of total hip arthroplasty, surgical technique, mean follow-up, and outcomes.
RESULTS
Overall, the mean age at total hip arthroplasty for pediatric hip disease is in the sixth and seventh decade, except for tumors and skeletal dysplasias. The reason for performing total hip arthroplasty is often osteoarthrosis and abnormal anatomy. Prosthesis types change based on patient's conditions and technological advances; custom-made implants are used for tumors, juvenile rheumatoid arthritis, and skeletal dysplasias; for other diseases, the most frequent are modular cementless implants. Outcomes are generally good, and all studies portray functional and pain improvements.
CONCLUSION
Total hip arthroplasty is performed more frequently than in the past in patients with pediatric hip pathologies; it enhances patients' quality of life by reducing pain and improving function. However, revision rate in these patients is not negligible.
PubMed: 38567046
DOI: 10.1177/18632521241229608 -
JIMD Reports Mar 2024Mucopolysaccharidoses (MPS) screening is tedious and still performed by analysis of total glycosaminoglycans (GAG) using 1,9-dimethylmethylene blue (DMB) photometric...
Mucopolysaccharidoses (MPS) screening is tedious and still performed by analysis of total glycosaminoglycans (GAG) using 1,9-dimethylmethylene blue (DMB) photometric assay, although false positive and negative tests have been reported. Analysis of differentiated GAGs have been pursued classically by gel electrophoresis or more recently by quantitative LC-MS assays. Secondary elevations of GAGs have been reported in urinary tract infections (UTI). In this manuscript, we describe the diagnostic accuracy of urinary GAG measurements by LC-MS for MPS typing in 68 untreated MPS and mucolipidosis (ML) patients, 183 controls and 153 UTI samples. We report age-dependent reference values and cut-offs for chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS) and keratan sulfate (KS) and specific GAG ratios. The use of HS/DS ratio in combination to GAG concentrations normalized to creatinine improves the diagnostic accuracy in MPS type I, II, VI and VII. In total 15 samples classified to the wrong MPS type could be correctly assigned using HS/DS ratio. Increased KS/HS ratio in addition to increased KS improves discrimination of MPS type IV by excluding false positives. Some samples of UTI patients showed elevation of specific GAGs, mainly CS, KS and KS/HS ratio and could be misclassified as MPS type IV. Finally, DMB photometric assay performed in MPS and ML samples reveal four false negative tests (sensitivity of 94%). In conclusion, specific GAG ratios in complement to quantitative GAG values obtained by LC-MS enhance discrimination of MPS types. Exclusion of patients with UTI improve diagnostic accuracy in MPS IV but not in other types.
PubMed: 38444580
DOI: 10.1002/jmd2.12412 -
JIMD Reports Mar 2024Lysosomal storage disorders (LSDs) in adults have milder phenotype and variable age at presentation. Several studies have described the phenotype, genotype and treatment...
Lysosomal storage disorders (LSDs) in adults have milder phenotype and variable age at presentation. Several studies have described the phenotype, genotype and treatment outcomes for adult-onset LSDs like Gaucher, Fabry, Pompe disease and others. We describe the first systematic study on the occurrence of LSDs in an adult population from India. It describes, the key clinical signs seen in these patients and those from literature review that can aid in early detection. Of 2102 biochemically diagnosed LSDs cases, 32 adult patients were identified with LSDs. Based on the clinical suspicion, screening test and enzyme study was carried out. Twenty-two patients were subjected to a genetic study to identify the causative variant in a respective gene. Of the 32 adult patients, we observed a maximum percentage of 37.5% ( = 12) cases with Gaucher disease, followed by 13% ( = 4) with Fabry disease. We found 10% of cases with MPS IVA and MPS I, and 9% cases with Pompe. Single case of adult mucolipidosis III and two cases each of Type 1 Sialidosis, Niemann-Pick disease B and metachromatic leukodystrophy were identified. We observed two common variants p.Leu483Pro and p.Ala487Thr in the gene in 23% of Indian patients with adult Gaucher disease. No common variants were observed in other aforementioned LSDs. Study identified 50% of Fabry patients and 4% of Gaucher patients diagnosed at our centre to be adults. The prevalence of adult Pompe patients was low (3.4%) as compared to 80% reported in the Caucasian population. Adult LSDs such as, MPS III, GM1/GM2 gangliosidosis and Krabbe disease were not identified in our cohort.
PubMed: 38444573
DOI: 10.1002/jmd2.12407 -
Cellular and Molecular Gastroenterology... 2024Microvillus inclusion disease (MVID) is a rare condition that is present from birth and affects the digestive system. People with MVID experience severe diarrhea that is... (Review)
Review
Microvillus inclusion disease (MVID) is a rare condition that is present from birth and affects the digestive system. People with MVID experience severe diarrhea that is difficult to control, cannot absorb dietary nutrients, and struggle to grow and thrive. In addition, diverse clinical manifestations, some of which are life-threatening, have been reported in cases of MVID. MVID can be caused by variants in the MYO5B, STX3, STXBP2, or UNC45A gene. These genes produce proteins that have been functionally linked to each other in intestinal epithelial cells. MVID associated with STXBP2 variants presents in a subset of patients diagnosed with familial hemophagocytic lymphohistiocytosis type 5. MVID associated with UNC45A variants presents in most patients diagnosed with osteo-oto-hepato-enteric syndrome. Furthermore, variants in MYO5B or STX3 can also cause other diseases that are characterized by phenotypes that can co-occur in subsets of patients diagnosed with MVID. Recent studies involving clinical data and experiments with cells and animals revealed connections between specific phenotypes occurring outside of the digestive system and the type of gene variants that cause MVID. Here, we have reviewed these patterns and correlations, which are expected to be valuable for healthcare professionals in managing the disease and providing personalized care for patients and their families.
Topics: Humans; Mucolipidoses; Microvilli; Malabsorption Syndromes; Phenotype; Animals; Myosin Type V; Mutation; Genetic Predisposition to Disease
PubMed: 38307491
DOI: 10.1016/j.jcmgh.2024.01.015 -
Pediatrics and Neonatology Mar 2024
Topics: Female; Humans; Hydrops Fetalis; Mucolipidoses
PubMed: 38296756
DOI: 10.1016/j.pedneo.2022.05.023 -
Children (Basel, Switzerland) Dec 2023Congenital dermal melanocytosis (DM) represents a common birthmark mainly found in children of Asian and darker skin phototype descent, clinically characterized by an...
Congenital dermal melanocytosis (DM) represents a common birthmark mainly found in children of Asian and darker skin phototype descent, clinically characterized by an oval blue-grey macule or macules, commonly located on the lumbosacral area. In rare DM cases, when presenting with diffuse macules persisting during the first years of life, it could represent a cutaneous feature of mucopolysaccharidoses (MPS). Extensive congenital DM is actually associated with Hurler syndrome (MPS type I) and Hunter syndrome (MPS type II), although several reports also described this association with MPS type VI and other lysosomal storage disorders (LySD), including GM1 gangliosidosis, mucolipidosis, Sandhoff disease, and Niemann-Pick disease. Here, we present the case of a two-year-old boy presenting with extensive dermal melanocytosis, generalized hypertrichosis, and chronic itch, harboring a heterozygous variant of uncertain significance, NM_152419.3: c.493C>T (p.Pro165Ser), in the exon 4 of gene, whose mutations are classically associated with MPS IIIC, also known as Sanfilippo syndrome. This is the first report that highlights the association between extensive congenital DM and MPS type IIIC, as well as a pathogenetic link between heterozygous LySD carrier status and congenital DM. We speculate that some cases of extensive congenital DM could be related to heterozygous LySD carriers, as a manifestation of a mild clinical phenotype.
PubMed: 38136122
DOI: 10.3390/children10121920 -
Genetics and Molecular Biology 2023Mucolipidosis II and III (MLII and MLIII) are autosomal recessive diseases caused by pathogenic variants in GNPTAB and GNPTG genes that lead to defects in...
Mucolipidosis II and III (MLII and MLIII) are autosomal recessive diseases caused by pathogenic variants in GNPTAB and GNPTG genes that lead to defects in GlcNAc-1-phosphotransferase. This enzyme adds mannose 6-phosphate residues to lysosomal hydrolases, which allows enzymes to enter lysosomes. Defective GlcNAc-1-phosphotransferase causes substrate accumulation and inflammation. These diseases have no treatment, and we hypothesized that the use of substrate reduction therapy and immunomodulation may be beneficial at the cell level and as a future therapeutic approach. Fibroblasts from two patients with MLIII alpha/beta and 2 patients with MLIII gamma as well as from one healthy control were treated with 10 µM miglustat, 20 µM genistein, and 20 µM thalidomide independently. ELISA assay and confocal immunofluorescence microscopy were used to evaluate the presence of heparan sulfate (HS) and the impact on substrate accumulation. ELISA assay showed HS reduction in all patients with the different treatments used (p=0.05). HS reduction was also observed by immunofluorescence microscopy. Our study produced encouraging results, since the reduction in substrate accumulation, even partial, may offer benefits to the phenotype of patients with inborn errors of metabolism.
PubMed: 38047750
DOI: 10.1590/1678-4685-GMB-2023-0117 -
Data in Brief Dec 2023Retinal degenerative diseases (RDDs) are a diverse group of retinal disorders that cause visual impairment. While RDD prevalence is high, little is known about the...
Retinal degenerative diseases (RDDs) are a diverse group of retinal disorders that cause visual impairment. While RDD prevalence is high, little is known about the molecular mechanisms underlying the pathogenesis within many of these disorders. Here we use transcriptome analysis to elucidate the molecular mechanisms that drive early onset photoreceptor neuron function loss in the mouse model of the RDD Mucolipidosis type IV (MLIV). MLIV is a lysosomal storage disorder resulting from loss of function mutations in the gene. encodes a lysosomal cation channel, the transient receptor potential channel mucolipin 1 (Trpml1). To identify changes in gene expression during onset in MLIV we used a genetic mouse model () which recapitulates clinical attributes of the human disease. We conducted transcriptome analysis in 6-week old control and mice under normal 12:12 light cycle as well as low and high light stress conditions. These data will be valuable to the vision research community for identifying differentially expressed in early onset MLIV potentially leading to new insights into the pathophysiology of this RDD. Raw FASTQ files and processed counts files for the RNA-seq libraries are deposited in the NCBI Sequence Read Archive (SRA) and have been assigned BioProject accession PRJNA1002601 [1].
PubMed: 38020430
DOI: 10.1016/j.dib.2023.109659