PMC4766941_01
Histochemical, clinical and molecular characterization of NLSDM patient.. Light microscopy of frozen transverse sections of skeletal muscle biopsy stained with Gomori trichrome (A) and Oil Red O (B) show an increase of lipid droplets; electron microscopy reveals massive line-up of lipid droplets without signs of mitochondrial alteration (C).Whole-body MRI showing: in (D) mild fatty infiltration of trapezius, deltoid and infraspinatus muscles; in (E) the posterior thigh muscles (hamstring, semimembranosus and semitendinosus) more severely involved than the quadriceps; in (F)severe fatty infiltration of leg muscles, with partial saving of anterior and posterior tibialis; and in (G) the diffuse involvement of the gluteus muscles. Electropherogram of PNPLA2 exon 2 sequence with the c.41_47delGCTGCGG homozygous mutation in patient (H); wild type sequence of exon 2 in a control subject in (I).
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A muscle biopsy revealed numerous vacuoles (Fig. 1A) positive to lipid staining in most fibers (Fig. 1B). Electron microscopy showed numerous lipid droplets between myofibrils in most fibers, often causing sarcomere disorganization; while mitochondria were normal (Fig 1C). A neutral lipid storage myopathy was hypothesized and molecular analysis of the PNPLA2 gene revealed a homozygous novel deletion of seven nucleotides in exon 2 (c.41_47delGCTGCGG) (Fig 1H). Whole-body MRI detected mild fatty infiltration of bilateral trapezius, deltoid and infraspinatus; severe fatty degeneration of pelvic girdle muscles, hamstring, semimembranosus and semitendinosus; diffuse fatty infiltration of leg muscles with partial saving of anterior and posterior tibialis (Fig 1D-G).
Left ventricle fibrosis detected by cardiovascular magnetic resonance.. Contrast-enhanced inversion-recovery gradient-echo images of left ventricle (basal portion, panel A and middle portion, panel B) in short-axis views, showing subepicardial late gadolinium enhancement of interventricular septum (arrows) and meso-subepicardial late gadolinium enhancement of anterior-lateral free wall (head arrows). LV = left ventricle.
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Cardiac MRI detected left ventricular dilation with diffused hypokinesia, moderate-severe reduction of left ventricular systolic function (ejection fraction FE 36%) and fibrosis of cardiac wall, without fatty infiltration (Fig. 2).