Muscle MRI in neutral lipid storage disease (NLSD)

Matteo Garibaldi,Elena Maria Pennisi,Lorenzo Maggi,Elisabetta Tasca,Simonetta Gerevini,Donatella Pantoli,Olimpia Musumeci,Antonio Toscano,Giorgio Tasca,Pierfancesco Ottaviani,Jordi Diaz-Manera,Roberto Massa,Francesco Laschena,Claudio Bruno,Giovanni Antonini,Chiara Fiorillo,Enrico Bertini,Adele D’Amico,Corrado Angelini

doi:10.1007/s00415-017-8498-8

Abstract

Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism resulting in lipid droplets accumulation in different tissues. Skeletal muscle could be affected in both two different form of disease: NLSD with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle imaging data of 12 patients from the Italian Network for NLSD: ten patients presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus, semimembranosus, soleus and gastrocnemius medialis in the lower limbs and infraspinatus in the upper limbs were the most affected muscles. Gracilis, sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid were spared. Muscle involvement was not homogenous and characteristic “patchy” replacement was observed in at least one muscle in all the patients. Half of the patients showed one or more STIR positive muscles. In both NLSD-I cases muscle involvement was not observed by T1-TSE sequences, but one of them showed positive STIR images in more than one muscle in the leg. Our data provides evidence that muscle imaging can identify characteristic alterations in NLSD-M, characterized by a specific pattern of muscle involvement with “patchy” areas of fatty replacement. Larger cohorts are needed to assess if a distinct pattern of muscle involvement exists also for NLSD-I.

Highlights

Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism characterized by a defect in the catabolic pathway of triacylglycerols resulting in systemic accumulation of triglycerides in cytoplasmic droplets, notably in the leukocytes (Jordan’s anomaly)
Two different recessive forms have been described: (1) the NLSD with myopathy (NLSD-M) caused by molecular defects in the adipose triglyceride lipase gene (ATGL, called patatin-like phospholipase domaincontaining 2, PNPLA2) coding for a rate-limiting enzyme catalyzing the first step of hydrolysis of triglycerides [1], and (2) the NLSD with ichthyosis (NLSD-I or Chanarin-Dorfman Disease) due to mutations in the ABHD5 gene coding an homonymous activator protein of ATGL [2]
We present a systematic study of muscle imaging in a large cohort of NLSD patients

Summary

Introduction

Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism characterized by a defect in the catabolic pathway of triacylglycerols resulting in systemic accumulation of triglycerides in cytoplasmic droplets, notably in the leukocytes (Jordan’s anomaly). Typical NLSD-I presentation include an early onset ichthyosis (nonbullous congenital ichthyosiform erythroderma, NCIE) associated with liver and mild skeletal muscle involvement [3]. Evidence is accumulating on the usefulness of muscle imaging in defining specific patterns of muscle involvement in inherited muscle diseases to help clinicians in the diagnostic workup [5,6,7]. Metabolic myopathies have not yet been widely investigated and most of the studies concern Pompe Disease, which present a characteristic pattern of muscle involvement [8,9,10]

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