Atypical presentation of GNE myopathy with asymmetric hand weakness

Dios, John Karl L. de; Shrader, Joseph A.; Joe, Galen O.; McClean, Jeffrey C.; Williams, Kayla; Evers, Robert; Malicdan, May Christine V.; Ciccone, Carla; Mankodi, Ami; Huizing, Marjan; McKew, John C.; Bluemke, David A.; Gahl, William A.; Carrillo-Carrasco, Nuria

doi:10.1016/j.nmd.2014.07.006

Cited by 20 publications

(11 citation statements)

References 22 publications

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“…Both extremes of muscle overuse or underuse (such as fractures or prolonged inactivity) may increase the rate of progression. Severe and prolonged muscle overuse, associated with intense pain, has been shown to cause significant weakness and atrophy of muscles involved in work-related repetitive muscle overuse in a patient with GNE myopathy [18]. A balanced physical activity, which includes regular exercise, as feasible and tolerated, should be encouraged in patients with GNE myopathy, with the possible exception of lifting weights.…”

Section: Clinical Manifestations Of Gne Myopathymentioning

confidence: 99%

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

2018

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GNE myopathy, previously known as hereditary inclusion body myopathy (HIBM), or Nonaka myopathy, is a rare autosomal recessive muscle disease characterized by progressive skeletal muscle atrophy. It has an estimated prevalence of 1 to 9:1,000,000. GNE myopathy is caused by mutations in the GNE gene which encodes the rate-limiting enzyme of sialic acid biosynthesis. The pathophysiology of the disease is not entirely understood, but hyposialylation of muscle glycans is thought to play an essential role. The typical presentation is bilateral foot drop caused by weakness of the anterior tibialis muscles with onset in early adulthood. The disease slowly progresses over the next decades to involve skeletal muscles throughout the body, with relative sparing of the quadriceps until late stages of the disease. The diagnosis of GNE myopathy should be considered in young adults presenting with bilateral foot drop. Histopathologic findings on muscle biopsies include fiber size variation, atrophic fibers, lack of inflammation, and the characteristic Brimmed^vacuoles on modified Gomori trichome staining. The diagnosis is confirmed by the presence of pathogenic (mostly missense) mutations in both alleles of the GNE gene. Although there is no approved therapy for this disease, preclinical and clinical studies of several potential therapies are underway, including substrate replacement and gene therapy-based strategies. However, developing therapies for GNE myopathy is complicated by several factors, including the rare incidence of disease, limited preclinical models, lack of reliable biomarkers, and slow disease progression.

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Section: Clinical Manifestations Of Gne Myopathymentioning

confidence: 99%

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

2018

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“…Cardiac and respiratory functions are typically spared. Some cases present with proximal leg weakness,3,4 finger weakness,5 or calf atrophy 4. Rimmed vacuoles on muscle pathology are a clue for a diagnosis of GNE myopathy, while it is not detected in all cases of genetically confirmed GNE myopathy.…”

Section: Introductionmentioning

confidence: 99%

Progression of GNE Myopathy Based on the Patient-Reported Outcome

et al. 2019

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Background and Purpose GNE myopathy is a rare progressive myopathy caused by biallelic mutations in the GNE gene, and frequently accompanied by rimmed vacuoles in muscle pathology. The initial symptom of foot drop or hip-girdle weakness eventually spreads to all limbs over a period of decades. Recent advances in pathophysiologic research have facilitated therapeutic trials aimed at resolving the core biochemical defect. However, there remains unsettled heterogeneity in its natural course, which confounds the analysis of therapeutic outcomes. We performed the first large-scale study of Korean patients with GNE myopathy. Methods We gathered the genetic and clinical profiles of 44 Korean patients with genetically confirmed GNE myopathy. The clinical progression was estimated retrospectively based on a patient-reported questionnaire on the status of the functional joint sets and daily activities. Results The wrist and neck were the last joints to lose antigravity functionality irrespective of whether the weakness started from the ankle or hip. Two-thirds of the patients could walk either independently or with an aid. The order of losing daily activities could be sorted from standing to eating. Patients with limb-girdle phenotype showed an earlier age at onset than those with foot-drop onset. Patients with biallelic kinase domain mutations tended to progress more rapidly than those with epimerase and kinase domain mutations. Conclusions The reported data can guide the clinical management of GNE myopathy, as well as provide perspective to help the development of clinical trials.

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“…MD of caveolinopathy appears to lack specificity, so it should be distinguished from other distal myopathies . Tibialis anterior muscles are affected in Nonaka myopathy, and asymmetric distal muscle involvement has been reported . However, rimmed vacuoles are also detected in muscle biopsies of this myopathy .…”

Section: Discussionmentioning

confidence: 96%

Mutation in the caveolin‐3 gene causes asymmetrical distal myopathy

et al. 2016

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Mutations in the gene encoding caveolin-3 (CAV3) can cause a broad spectrum of clinical phenotypes, including limb girdle muscular dystrophy, rippling muscle disease, distal myopathy (MD), idiopathic persistent elevation of serum creatine kinase and cardiomyopathy. MD is a relatively rare subtype of caveolinopathy. Here, we report a sporadic case of a middle-aged female Chinese patient with MD in which a CAV3 mutation was identical to that previously reported in cases of rippling muscle disease. T1-weighted enhanced skeletal muscle MRI of the lower limbs showed an abnormal signal in the distal and proximal muscles. A muscle biopsy revealed moderate dystrophic changes, and immunohistochemical staining showed reduced CAV-3 expression in the plasmalemma. Genetic analysis revealed a heterozygous c.136G > A (p.Ala46Thr) CAV3 mutation that appeared to be de novo because it was absent from the patient's parents. This study suggested that the CAV3 c.136G > A (p.Ala46Thr) mutation can cause MD as well as different phenotypes in different individuals, suggesting that additional unknown loci must affect the disease phenotypes.

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Atypical presentation of GNE myopathy with asymmetric hand weakness

Cited by 20 publications

References 22 publications

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

Progression of GNE Myopathy Based on the Patient-Reported Outcome

Mutation in the caveolin‐3 gene causes asymmetrical distal myopathy

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