Adolescent with neutral lipid storage disease with myopathy caused by a new mutation of the PNPLA2 gene – a dietetic attempt

Background: Slowly progressive neutral lipid storage diseases (NLSDs) are more likely diagnosed at the adult. The typical histological finding is massive lipid storage. Since now rarely described mutations of the “patatin-like phospholipase domain-containing protein 2” (PNPLA2) gene cause NLSD with myopathy (NLSDM). Hepatomegaly or steatosis hepatitis, diabetes mellitus, hypertriglyceridemia, and dilated cardiomyopathy (CMP) may be further symptoms.

Case Report: 7-year-old boy with normal motoric abilities and hyperCKemia ca. 1,500 U/L. Pathological muscular biopsy with atrophic fibers in polygonal configuration, massive lipid storage, and autophagic vacuoles most notably in type 1-fibers. Because of slightly decreased muscular carnitine level, an isolated carnitine-transporter defect was assumed. During 7 years, there was no further clinical symptoms beside a marked hyperCKemia with muscular edema in MRI. Acylcarnitine spectrum and carnitine in plasma with and without substitution were normal. At the age of 16 years, diagnosis of arterial hypertonia with hypertrophic CMP. Thus, a re-evaluation of the diagnose followed demonstration of vacuoles in leucocytes (Jordan-anomaly), increase of muscular edema, and lipid storage in mMRI. Under suspicion of a NLSDM, a new homozygous stop mutation (p.Glu31X-/E31X) in exon 2 of the PNPLA2 gene could be found. So far, there was no sign of steatosis hepatis; cardio-MRI with slightly hypertrophic CMP. No progressive cardiovascular problems under antihypertensive therapy. No exercise intolerance. We report our experience with triglyceride-reduced, MCT-enriched diet.

Conclusion: A markedly elevation of muscular enzymes may be the single symptom of the rare NLSDM in childhood. The leading diagnostic finding is lipid accumulation in leucocytes and muscle. Molecular genetical confirmation of the diagnosis with testing the PNPLA2 gene. The effect of triglyceride-reduced, MCT-enriched diet has to be awaited.