J Clin Neurol.  2019 Jul;15(3):275-284. 10.3988/jcn.2019.15.3.275.

Progression of GNE Myopathy Based on the Patient-Reported Outcome

• Park YE
• Kim DS
• Choi YC
• Shin JH

• KMID: 2451109
• DOI: http://doi.org/10.3988/jcn.2019.15.3.275

Abstract

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.

Keyword

nonaka type distal myopathy; limb-girdle muscular dystrophies; disease progression; mutation; surveys and questionnaires

MeSH Terms

Age of Onset
Ankle
Disease Progression
Eating
Extremities
Foot
Hip
Humans
Joints
Muscular Diseases*
Muscular Dystrophies, Limb-Girdle
Neck
Pathology
Phenotype
Phosphotransferases
Population Characteristics
Retrospective Studies
Surveys and Questionnaires
Vacuoles
Wrist
Phosphotransferases

Figure

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  Fig. 1 GNE mutations identified in our patients.

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  Fig. 2 Decrease in the number of functional joints. A: All of the functional joints in each of the patients. B: The functional joint sets were correlated with the disease duration (p<0.0001), and the mean yearly rate of decrease was −0.2581.

• 

  Fig. 3 Functional status during ambulation and daily activities. A: The disease duration clearly differed between the ambulatory and wheelchair-bound patients, at 4.5±0.7 and 17.4±2.2 years, respectively. B: All of the daily activities that could be performed independently by each of the patients. C: The number of independent daily activities was correlated with the disease duration (p=0.012). ADL: activities of daily living.

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  Fig. 4 Disease severity according to the types of initial symptoms. A: The onset age was significantly younger in the subgroup with limb-girdle phenotype. B: The duration from the onset to the diagnosis was significantly longer in the subgroup with limb-girdle phenotype. C and D: Disease progression as represented by the functional joint sets according to disease duration did not differ between the subgroups of foot-drop onset and limb-girdle phenotype (p=0.5731).

• 

  Fig. 5 Disease severity according to the domains of GNE mutations. A: The onset age did not differ significantly among the three subgroups of KD, ED/KD, and ED. B–D: Disease progression as represented by the number functional joint sets according to disease duration significantly rapid in the order of KD (B), ED/KD (C), and ED (D) (p=0.0062). ED: epimerase domain, KD: kinase domain.

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