Two Brothers With ADSS1 Myopathy: A Report of Clinical, Radiological, and Autopsy Findings.

ADSS1 myopathy, previously known as adenylosuccinate synthetase-like 1 (ADSSL1) myopathy, is an autosomal recessive muscle disease caused by variants in ADSS1 (adenylosuccinate synthase 1). ADSS1 myopathy is complicated by respiratory muscle weakness or cardiomyopathy as well as limb muscle weakness. We analyzed two siblings with ADSS1 myopathy, both harboring compound heterozygous pathogenic variants (c.

Long-term observation of patients with advanced late-onset Pompe disease undergoing enzyme replacement therapy: A 15-year observation in a single center.

Background: There have been few descriptions in the literature on long-term enzyme replacement therapy (ERT) in patients with advanced late-onset Pompe disease (LOPD).

Objectives: This study aimed to assess the efficacy and limitations of ERT in advanced LOPD patients.

Methods: We retrospectively reviewed the clinical courses of patients with advanced LOPD (two juvenile-onset and five adult-onset patients) who were treated with recombinant human alglucosidase alfa to examine improvements achieved with and limitations of ERT until their death or when switching to avalglucosidase alfa occurred.

Comprehensive Analysis of a Japanese Pedigree with Biallelic ACAGG Expansions in RFC1 Manifesting Motor Neuronopathy with Painful Muscle Cramps.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive multisystem neurologic disorder caused by biallelic intronic repeats in RFC1. Although the phenotype of CANVAS has been expanding via diagnostic case accumulation, there are scant pedigree analyses to reveal disease penetrance, intergenerational fluctuations in repeat length, or clinical phenomena (including heterozygous carriers). We identified biallelic RFC1 ACAGG expansions of 1000 ~ repeats in three affected siblings having sensorimotor neuronopathy with spinocerebellar atrophy initially presenting with painful muscle cramps and paroxysmal dry cough.

Factors influencing the decision to introduce alternative nutrition in patients with Duchenne muscular dystrophy.

Introduction/aims: Nutritional management of adults with Duchenne muscular dystrophy (DMD) is an important clinical issue. However, it is not clear which dysphagia-related factors should prompt introduction of alternative nutrition (AN). We aimed to determine which patients with DMD were introduced to AN.

Analysis of muscle magnetic resonance imaging of a large cohort of patient with VCP-mediated disease reveals characteristic features useful for diagnosis.

Background: The diagnosis of patients with mutations in the VCP gene can be complicated due to their broad phenotypic spectrum including myopathy, motor neuron disease and peripheral neuropathy. Muscle MRI guides the diagnosis in neuromuscular diseases (NMDs); however, comprehensive muscle MRI features for VCP patients have not been reported so far.

Methods: We collected muscle MRIs of 80 of the 255 patients who participated in the "VCP International Study" and reviewed the T1-weighted (T1w) and short tau inversion recovery (STIR) sequences.

Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan.

Background: A rare muscle disease, GNE myopathy is caused by mutations in the GNE gene involved in sialic acid biosynthesis. Our recent phase II/III study has indicated that oral administration of aceneuramic acid to patients slows disease progression.

Methods: We conducted a phase III, randomized, placebo-controlled, double-blind, parallel-group, multicenter study.

[Drugs for Genetic Myopathy].

Specific therapy for genetic myopathy is still limited to enzyme replacement therapy for Pompe disease with alglucosidase alfa and avalglucosidase alfa, and exon skipping therapy with antisense nucleotide viltolarsen for about 7% of patients with Duchenne muscular dystrophy. Corticosteroid treatment (predonisolone 10-15mg/day) to Duchenne muscular dystrophy, from the age of 5-6 years old, regardless of mutations. Continuation of corticosteroid after loss of ambulation is controversial.

Phase II/III Study of Aceneuramic Acid Administration for GNE Myopathy in Japan.

Background: GNE myopathy is an ultra-rare muscle disease characterized by a reduction in the synthesis of sialic acid derived from pathogenic variants in the GNE gene. No treatment has been established so far.

Objective: We evaluated the safety and efficacy of oral supplementation of aceneuramic acid in patients with GNE myopathy.

Clinical characteristics of dysphagic inclusion body myositis.

This study aimed to characterize dysphagic patients with inclusion body myositis (IBM) with cricopharyngeal bar (CPB) (n = 17; IBM-CPB(+)) by comparing their swallowing function and muscle magnetic resonance imaging data with IBM patients without CPB (n = 28; IBM-CPB(-)). IBM-CPB(+) patients were older at diagnosis and had more frequent obstruction-related dysphagia and stronger knee extension than IBM-CPB(-) patients. IBM-CPB(+) patients also had less intramuscular fatty infiltration than IBM-CPB(-) patients on T1-weighted magnetic resonance images of the rectus femoris (2.

Multidimensional analyses of the pathomechanism caused by the non-catalytic GNE variant, c.620A>T, in patients with GNE myopathy.

GNE myopathy is a distal myopathy caused by biallelic variants in GNE, which encodes a protein involved in sialic acid biosynthesis. Compound heterozygosity of the second most frequent variant among Japanese GNE myopathy patients, GNE c.620A>T encoding p.

Distinctive chaperonopathy in skeletal muscle associated with the dominant variant in DNAJB4.

DnaJ homolog, subfamily B, member 4, a member of the heat shock protein 40 chaperones encoded by DNAJB4, is highly expressed in myofibers. We identified a heterozygous c.270 T > A (p.

[Pompe Disease: Extraordinary Measures].

Extraordinary Measures is a 2010 film about parents who tried to develop a drug with a glycobiology scientist to save their children suffering from a milder subtype of infantile Pompe disease (non-classic infantile-onset form), which can be said as an intermediate type between infantile onset and late-onset types. This movie is based on a nonfiction book The Cure by Geeta Anand. Pompe disease (glycogen storage disease type 2) is a myopathy, that affects the diaphragm.

Long-term evaluation parameters in GNE myopathy: a 5-year observational follow-up natural history study.

Background: A number of clinical trials targeting GNE myopathy patients have been conducted. However, useful clinical parameters for postmarketing surveillance and long-term clinical observation have not yet been established.

Objective: We conducted a 5-year observational follow-up natural history study to identify evaluation parameters, which may be useful for the long-term observation of GNE myopathy patients.

Simultaneous measurement of the size and methylation of chromosome 4qA-D4Z4 repeats in facioscapulohumeral muscular dystrophy by long-read sequencing.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder characterized by asymmetric muscle wasting and weakness. FSHD can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in SMCHD1, DNMT3B, or LRIF1. Genetic diagnosis of FSHD is challenging because of the complex procedures required.

RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy.

Dystrophinopathy is caused by alterations in DMD. Approximately 1% of patients remain genetically undiagnosed, because intronic variations are not detected by standard methods. Here, we combined laboratory and in silico analyses to identify disease-causing genomic variants in genetically undiagnosed patients and determine the regulatory mechanisms underlying abnormal DMD transcript generation.

A 78-year-old Japanese male with late-onset PHKA1-associated distal myopathy: Case report and literature review.

PHKA1 mutations are causative for glycogen storage disease type IXd (GSDIXd), a myopathy that can be asymptomatic or associated with exercise intolerance, and rarely is accompanied by weakness or atrophy of limbs. Here we report a patient with GSDIXd who developed distal myopathy which was not accompanied by exercise intolerance at age 71. Muscle MRI revealed severe but gradual involvement of muscles with disease progression in the order of medial gastrocnemius, soleus, lateral gastrocnemius, and gluteus muscles.

Myoglobinopathy affecting facial and oropharyngeal muscles.

Myoglobinopathy is a rare autosomal dominant myopathy that manifests in adulthood with proximal and axial weakness and variable respiratory and cardiac failure. Muscle pathology features associated with myoglobinopathy include characteristic sarcoplasmic bodies in skeletal and cardiac muscles. Here we present the first case of myoglobinopathy in an Asian individual.

Sick sinus syndrome concomitant with myopathy associated with anti-mitochondrial antibodies: a case report.

Background: Anti-mitochondrial antibody (AMA)-associated myopathy is known to be concomitant with primary biliary cirrhosis and to cause both skeletal muscle disorders and arrhythmias, myocardium disorders, and respiratory muscle disorders. We report a case of AMA-associated myopathy in which the bradycardia-related symptoms preceded the skeletal muscle symptoms.

Case Summary: A 59-year-old woman visited the emergency room in our hospital following a syncopal event.

Unique Lewy pathology in myotonic dystrophy type 1.

Lewy body-related α-synucleinopathy (Lewy pathology) has been reported in patients with myotonic dystrophy (DM) type 1 (DM1), but no detailed report has described the prevalence and extent of its occurrence. We studied consecutive full autopsy cases of DM1 at the National Center of Neurology and Psychiatry (NCNP) Brain Bank for intractable psychiatric and neurological disorders. Thirty-two cases, genetically determined to be DM1 (59.

Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy.

Aims: Oculopharyngodistal myopathy (OPDM) is caused by the expansion of CGG repeats in NOTCH2NLC (OPDM_NOTCH2NLC) GIPC1 (OPDM_GIPC1), or LRP12 (OPDM_LRP12). Neuronal intranuclear inclusion disease (NIID) is clinically distinct from OPDM but is also caused by the expansion of CGG repeats in NOTCH2NLC, which may be an indicator of intranuclear inclusion in skin biopsy. We investigated the presence of intranuclear inclusions in skin biopsies from patients with OPDM and muscle diseases with a similar pathology to evaluate whether they will have similar diagnostic findings on skin biopsy.

A case of delayed diagnosis of Becker muscular dystrophy due to underlying developmental disorders.

Background: Developmental disorders associated with Becker muscular dystrophy (BMD), possibly resulting from a lack of dystrophin in the brain, have been reported, but their importance is not fully understood. We report a case of a BMD patient who had been socially withdrawn due to mental retardation and autism spectrum disorder and could not receive appropriate medical services, resulting in delayed detection of severe cardiomyopathy and embolic strokes which developed as complications of BMD.

Case Report: The case is a 41-year-old male.