Clinical Guidance

Because reports of GNE myopathy consist mainly of single individuals or relatively small series, correlations between genotype and phenotype are difficult.

Source: GeneReviews — "GNE Myopathy"

Penetrance

Penetrance of biallelic GNE pathogenic variants is likely close to 100%. Only two older individuals with biallelic GNE pathogenic variants have been reported to be asymptomatic: One (age 67 years) was homozygous for the common Middle Eastern variant and one (age 60 years) was homozygous for the common Japanese variant .

Source: GeneReviews — "GNE Myopathy"

Diagnostic Criteria

Suggestive Findings

GNE myopathy should be suspected in individuals with the following findings.

Clinical findings

• Myopathy presenting in young adults with bilateral foot drop caused by anterior tibialis weakness, followed by slowly progressive skeletal muscle weakness. Although there is relative sparing of the quadriceps, they may become affected at late stages of the disease. The clinical picture varies depending on the stage of disease progression at which individuals are evaluated .

• Serum CK may be normal or up to four times the upper limit of normal.

Muscle histopathology

Source: GeneReviews — "GNE Myopathy"

Differential Diagnosis

The differential diagnosis includes adult-onset distal myopathies and myopathies with rimmed vacuoles . Table 2. Genes of Interest in the Differential Diagnosis of GNE Myopathy

Management Guidelines

Individuals with GNE myopathy are often evaluated and managed by a multidisciplinary team that includes clinical geneticists, neuromuscular specialists, physiatrists, physical and occupational therapists, and if needed, pulmonologists. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with GNE myopathy, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with GNE Myopathy

Clinical Guidance

It may be prudent to use medications/drugs with potential myotoxicity (e.g., colchicine, statins) with caution. It is strongly recommended that affected individuals have a healthy diet and exercise to avoid developing hypercholesterolemia, in an effort to reduce the risk associated with taking statins. Individuals with GNE myopathy should avoid lifting weights and performing repetitive activities that result in muscle pain.

Source: GeneReviews — "GNE Myopathy"

Therapies Under Investigation

N-acetylmanossamine (ManNAc) is the only therapy currently in clinical development for GNE myopathy [, , , ]. Ultragenyx discontinued the clinical development of extended-release sialic acid (Ace-ER) in 2017 following a Phase III trial that failed to detect clinical efficacy . Preclinical studies are ongoing to advance gene therapy as a potential therapy for GNE myopathy. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "GNE Myopathy"

Surveillance Guidelines

Routine follow up with the multidisciplinary team is recommended annually, or more frequently as determined by managing physician . Table 5. Recommended Multidisciplinary Team Surveillance for Individuals with GNE Myopathy

Source: GeneReviews — "GNE Myopathy"