2026-03-30 | Ultrasound-guided one-point puncture lumbosacral plexus block combined with laryngeal mask airway general anesthesia for thigh amputation in a patient with mucopolysaccharidosis: a case report.
Mucopolysaccharidosis (MPS) is a group of rare inherited lysosomal storage disorders caused by deficiencies of specific enzymes, leading to abnormal accumulation of glycosaminoglycans in tissues throughout the body. It is often associated with a difficult airway, cervical spine instability, restrictive pulmonary dysfunction, and cardiovascular pathologies, which significantly increase perioperative risks. This manuscript reports a case of a 36-year-old male MPS patient (clinical phenotype highly suggestive of type IV) who underwent right mid-to-upper thigh amputation for a pathological fracture of the right femur. Given his potential difficult airway (Mallampati class III, thyromental distance <6 cm), mild kyphosis, and restrictive pulmonary dysfunction, the anesthetic plan consisted of an ultrasound-guided one-point puncture, dual-target lumbosacral plexus block (35 mL of 0.15% ropivacaine) combined with supraglottic airway (laryngeal mask airway, LMA) under general anesthesia. The block successfully provided an L2-S3 sensory level and served as the basis for postoperative multimodal analgesia. The surgery lasted 2 h with 500 mL blood loss, requiring 2 units of red blood cells. Hemodynamics remained stable, and no additional muscle relaxants were administered. The patient regained consciousness and the LMA was removed 10 min postoperatively. The Numerical Rating Scale (NRS) pain scores at 2, 6, 12, and 24 h postoperatively were 2, 3, 2, and 1, respectively. Functional exercise began on postoperative day 1 without major complications. The patient was discharged 15 days after surgery and was hospitalized for a total of 18 days. With strict patient selection and thorough preparation of emergency airway protocols, combining an LMA with an ultrasound-guided one-point puncture lumbosacral plexus block can be a safe and feasible individualized anesthetic strategy for lower limb proximal surgery in MPS patients. This approach helps avoid intubation risks, reduces opioid consumption, and promotes early recovery. However, due to the considerable difficulty of airway management in patients with MPS, elective surgery requires multidisciplinary consultation and comprehensive airway assessment to ensure perioperative safety.
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2026-03-05 | P044: First report of GLP-1 agonist use in MCAD deficiency
Case Presentation: A 29-year-old Hispanic female presented with a clinical and biochemical diagnosis of MPSIVA.She has short stature, mild corneal clouding, pectus carinatum, required multiple knee surgeries and her x-ray showed bullet shaped vertebrae.This individual had two affected siblings with MPSIVA who are unavailable for testing.Her mother is mildly affected and presents with corneal clouding and short stature.Diagnostic Workup: This individual initially had an LSD panel which identified one pathogenic variant in the GALNS gene, c.107T>C, which was insufficient to explain the patient's phenotype.ES with RNA-seq was ordered.RNA-seq analysis identified an 11 bp deletion in an alternative transcript (NM_001323544.2), leading to frameshift: p.(Gly43Aspfs*5).This aberrant transcript was a consequence of a single nucleotide change (c.121-210C>T) located in intron 1 and is 210 bp upstream of the splice acceptor site for exon 2 in the MANE transcript (NM_000512.5).As this variant is located at the startproximal nonsense-mediated mRNA decay insensitivity region, re-initiation of translation at the next in-frame start codon (p.47) is possible.This variant was originally classified as likely benign (LB) due to being observed at a frequency of 0.31% (523/166064 alleles) with the highest frequency noted in the African subpopulation at 3.05% in the gnomAD database.However, this variant has also been reported in the compound heterozygous and homozygous state in four individuals with MPSIVA and has been classified as a "Potentially Disease Associated Mutation" in the Human Gene Mutation Database.Based on the RNA-seq analysis and other affected individuals identified with this variant, the lab was able to upgrade the variant from LB to a variant of uncertain significance (VUS) and may represent a hypomorphic allele.Outcome and Follow-Up: The provider was able to provide this individual with a molecular diagnosis of MPSIVA based on the detection of two GALNS variants.Since then, we have tested the mildly affected mother who was found to be homozygous for the c.121-210C>T variant with consistent RNA-seq results to the proband.This strengthens the understanding that this is a hypomorphic allele.Testing the proband's siblings is still recommended. Conclusion:The use of ES with RNA-seq was able to identify a variant that was -210 nucleotides upstream of the splice acceptor site and lead to an upgrade in variant classification from LB to VUS.This highlights the diagnostic advantages of using RNA-seq over standard DNA-only testing methodology.RNAseq can aid in identifying aberrant splicing, mono-allelic expression, and aberrant expression which can increase diagnostic yield.Having a molecular diagnosis can provide individuals with different treatment options, including possible GT enrollment, and family planning options.
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2026-03-05 | Development and characterization of a model of mucopolysaccharidosis type IVA for evaluating therapies targeting bone disease.
Mucopolysaccharidosis type IVA (MPSIVA) is a lysosomal storage disease (LSD) caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which causes the accumulation of keratan sulphate (KS) and chondroitin sulphate (CS). Patients with MPSIVA typically present with severe skeletal and joint disorders, which are not addressed by conventional therapies. Currently, no animal model accurately replicates the human disease, hindering the development of novel therapeutic interventions. To overcome this limitation, we established, by CRISPR-Cas9 technology, a Galns-/- mouse model that expresses a non-functional enzyme and accumulates CS and KS in the urine, plasma and distinct tissues, and glycosaminoglycans in the spleen. The mice exhibit shortened long bones, trabecular bone alterations and skeletal abnormalities in the growth plate. Additionally, we observed increased levels of inflammatory and oxidative markers in visceral organs and plasma. Our newly developed model of MPSIVA demonstrates clear and quantifiable signs of skeletal alterations, providing novel means of assessment of the safety and efficacy of innovative therapies, including hematopoietic stem and progenitor cell gene therapy, which has recently been shown to provide a beneficial effect on skeletal alterations in Hurler syndrome.
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