Table 1 MIPEP variants in four unrelated patients from four unrelated families

Zygosity

Compound heterozygous

Compound heterozygous

Homozygous

Compound heterozygous

Nucleotide change(s)

c.1745 T > G; c.212 T > A

c.916C > T; c.1804G > T

c.1027A > G

c.1534C > G; NA

Protein change(s)

p.L582R; p.L71Q

p.L306F; p.E602*

p.K343E

p.H512D; NA

db SNP ID(s)

NA

rs143912947, NA

NA

NA

ExAC frequency

NA

8.2 × 10⁻⁶, NA

NA

3.2 × 10⁻⁵, NA

Mutation Taster

D

D

D

D, NA

SIFT

D

D

D

D

PolyPhen-2

0.99, 1.00

0.98, NA

0.97

1.00, NA

CADD 1.0 (Phred-like)

29.9, 28.0

29.5, 48

28.5

33, NA

Metabolic myopathy features

Examination of skeletal muscle showed:

1. Moderate variation in fiber size with type 1 fiber predominance

2. Many fibers with increase in subsarcolemmal oxidative activity

3. Increased mitochondria in many fibers by trichrome stain

4. Marked mitochondrial proliferation and pleomorphism on electron microscopy

5. Marked increase in lipid droplets on electron microscopy

Examination of quadriceps muscle by light microscopy showed:

1. Mild variation in fiber size; type 1 fiber predominance with type 1 to type 2 fiber ratio of 70:30

2. Diffuse, moderate to marked increase in glycogen stores on PAS special stain

Electron microscopy showed: membrane-bound glycogen deposits; diffuse, mild to moderate increase in lipid droplets on oil-red-O special stain and no increase in oxidative enzyme staining; no increase in mitochondria or mitochondrial pleomorphism, no evidence for a dystrophic process

NA

Light and electron microscopic findings of the skeletal muscle (diaphragm) and cardiac muscle showed:

1. Numerous lipid droplets, glycogen deposition (especially cardiac muscle), and large aggregates of mitochondria.

2. In the skeletal myofibers, the aggregates of mitochondria were often adjacent to vessels. Many of the mitochondria were quite enlarged and had bloated vesicular cristae

3. The ventricles showed thick trabeculae that spanned the lumen and focal clefts in their thick walls. The myofibers swirled and interlaced together. A few, scattered nuclei were enlarged and box-car shaped. Cross striations were well-preserved