Novel GNE mutations in two phenotypically distinct HIBM2 patients

Abstract

Homozygous mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene cause hereditary inclusion body myopathy type 2 (HIBM2). We describe two unrelated American patients with novel GNE mutations. While one patient followed a typical disease course for HIBM2 with an onset at age 25 and rimmed vacuole pathology on muscle biopsy, the second patient had several features atypical for HIBM2. This patient's onset was at age 55, included distal weakness, quadriceps sparing and respiratory insufficiency. His muscle biopsy showed prominent necrosis without rimmed vacuoles. This study expands the phenotype and illustrates the clinical spectrum of HIBM2 identified in a U.S. based neuromuscular clinic.

Figure 1

Ultrasonic imaging of quadriceps muscle from normal control or one of two HIBM2 patients. In patient 1, echogenicity is increased in the rectus femoris (RF) and vastus intermedius (VI) compared to the subcutaneous fat (SC). In contrast, only mild atrophy of the rectus femoris is seen in patient 2. Scale is 1 cm.

Figure 2

Muscle histochemistry with modified gomori trichrome (mGT) or hematoxylin and eosin (H&E) and immunohistochemistry with anti-LC3 or anti-Lamp2 of patient 1 (top) and patient 2 (bottom). Open arrows denote rimmed vacuoles, closed arrows mark LC3 positive inclusions and stars highlight necrotic fibers.