Neutral Lipid Storage Disease With Myopathy Research Articles

HyperCKemia: An early sign of childhood-onset neutral lipid storage disease with myopathy

Neutral lipid-storage disease with myopathy (NLSDM) is an autosomal recessive neuromuscular disorder caused by mutations in PNPLA2, and the average age at onset is 30 years. To date, only eight patients with childhood-onset NLSDM have been reported in detail. We investigated 3 unreported patients with NLSDM detected in childhood and reviewed 8 childhood-onset and 82 adult-onset patients with NLSDM documented in the literature. In the childhood-onset cohort, NLSDM presented initially as asymptomatic or paucisymptomatic hyperCKemia in 6/11 patients, and follow-up data showed onset of muscle weakness in 6/11 childhood-onset patients. In the adult-onset cohort, 95.1% (78/82) of patients showed muscle weakness. Cardiac involvement developed in 6/11 childhood-onset patients. Hepatomegaly was observed in 3/11 childhood-onset patients. Serum creatine kinase levels were elevated greater than five-fold of the upper limit of normal (ULN) in most childhood-onset patients and were elevated to less than ten-fold of the ULN in most adult-onset patients. Peripheral blood smears and muscle biopsies showed cytoplasmic lipid droplets in leukocytes and myocytes. NLSDM can present in children with asymptomatic or paucisymptomatic hyperCKemia before the onset of muscle weakness. The presence of lipid droplets in leucocytes (Jordans' anomaly) aids in diagnosing and confirming the pathogenicity of PNPLA2 variants of uncertain significance. There were no clear genotype-phenotype correlations in patients with NLSDM.

Neutral lipid storage disease with myopathy: A 10-year follow-up case report.

Mutations in PNPLA2 gene encoding for adipose triglyceride lipase (ATGL), involved in triglyceride degradation, lead to an inborn error of neutral lipid metabolism. The disorder that results in abnormal storage of neutral lipid is known as neutral lipid storage disease with myopathy (NLSDM). We report the follow-up of a 30-year-old woman with NLSDM, asymptomatic until age 23. At the age of 18, a high level of CPK and neutral lipid abnormal accumulation in muscle and skin cells suggested NLSDM diagnosis, afterwards confirmed by PNPLA2 analysis. After 5 years, she developed weakness in the upper and lower extremities. She was put on a low-fat diet with medium-chain triglycerides (MCT) oil supplementation but, although her CPK level decreased, myopathy continued to progress. At present, she presents severe skeletal myopathy without cardiac involvement. In this patient, no beneficial effects on progressive skeletal muscle weakness were detected after the MCT diet, probably due to complete loss of PNPLA2 expression.

A patient with neutral lipid storage disease with myopathy (NLSD-M): A clinical and genetic study

Neutral lipid storage disease with myopathy (NLSD-M) is an autosomal recessive disorder characterized by triglyceride-containing cytoplasmic droplets in leukocytes and muscle tissue. Usually, it presents with adult onset slowly progressive proximal muscle weakness associated with hypertrophic cardiomyopathy.

Case Report: PNPLA2 Gene Complex Heterozygous Mutation Leading to Neutral Lipid Storage Disease With Myopathy

Objective: To investigate the clinical features, skeletal muscle imaging, muscle pathology, blood smear and so on of neutral lipid storage disease with myopathy (NLSDM) caused by PNPLA2 gene mutation.Methods: The clinical data, skeletal muscle imaging, pathological data, and genetic test results of a patient with NLSDM treated in our hospital were collected in detail, and the previous literature was reviewed and compared.Results: The main symptoms were muscle weakness and muscular atrophy. Pathological findings of muscle biopsy showed fat deposition in muscle fibers with border cavitation. Fatty droplets were seen in the cytoplasm of neutrophils in peripheral blood. Magnetic resonance imaging of the muscles of both lower extremities showed that muscle in the thigh vastus intermedius, lateral muscles, biceps, and the muscle abdominal area of the middle leg were filled or replaced by fat. Genetic test results suggested mutations in the PNPLA2 gene.Conclusion: NLSDM is a rare clinical myopathy with abnormal lipid metabolism. Characteristic changes can be seen in skeletal muscle imaging and pathology. The detection of PNPLA2 gene mutation is an important basis for diagnosing NLSDM. Asymmetry and progressive limb weakness are the clinical features. Muscle MRI is mainly involved in the posterior group of the lower limbs. Jordans bodies in the peripheral blood smear and a large number of coarse-grained lipid deposits with rimmed vacuoles in muscle fibers are the characteristic pathological changes.

A novel PNPLA2 mutation causing total loss of RNA and protein expression in two NLSDM siblings with early onset but slowly progressive severe myopathy

Neutral lipid storage disease with myopathy (NLSDM) is a rare autosomal recessive disorder, due to an enzymatic error of lipid metabolism. Patients present always with skeletal muscle myopathy and variable cardiac and hepatic involvement. NLSDM is caused by mutations in the PNPLA2 gene, which encodes the adipose triglyceride lipase (ATGL). Here we report the molecular characterization and clinical findings of two NLSDM siblings carrying the novel c.187+1G > C homozygous PNPLA2 mutation, localized in the splice site of intron 2. Molecular analyses revealed that neither aberrant PNPLA2 mRNA isoforms, nor ATGL mutated protein were detectable in patient's cells.Clinically, both patients presented early onset muscle weakness, in particular of proximal upper limb muscles. In almost 15 years, muscle damage affected also distal upper limbs.This is a NLSDM family, displaying a severe PNPLA2 mutation in two siblings with clinical presentation characterized by an early onset, but a slowly evolution of severe myopathy.

Clinical findings and autophagic pathology in neutral lipid storage disease with myopathy.

Neutral lipid storage disease with myopathy (NLSDM) is a triglyceride metabolic disorder caused by defects of adipose triglyceride lipases (ATGL). The coexistence of lipid vacuoles and rimmed vacuoles in the myofibers is a characteristic pathological change in some NLSDM cases. However, it has not been explored whether autophagic abnormalities exist in the NLSDM myofibers with rimmed vacuole. Herein, we report that 5 patients with NLSDM initially presented with muscle weakness in the right arm related to long-term physical efforts, then developed muscle weakness of other limbs. Pathogenic mutations in the PNPLA2 gene were identified in all patients. Myopathological analysis showed a coexistence of massive lipid vacuoles and rimmed vacuoles, which was not associated with the age of onset or mutation sites, but closely related to the severity of muscle degeneration. The rimmed vacuoles showed strong immunopositivity to autophagic markers, but were negative to apoptotic markers. Significant immunoreactivity of p62 was observed in the rimmed vacuoles, while the lysosomal marker LAMP1 was severely decreased. Our study expanded the clinical and genetic spectrum of NLSDM. Loss of ATGL activity in muscle fibers with rimmed vacuoles induced a marked increase in autophagic formation, but lowered down the turnover of autolysosomes due to malfunction of lysosomes.

Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function.

Neutral lipid storage disease with myopathy (NLSDM) and with ichthyosis (NLSDI) are rare autosomal recessive disorders caused by mutations in the PNPLA2 and in the ABHD5/CGI58 genes, respectively. These genes encode the adipose triglyceride lipase (ATGL) and α-β hydrolase domain 5 (ABHD5) proteins, which play key roles in the function of lipid droplets (LDs). LDs, the main cellular storage sites of triacylglycerols and sterol esters, are highly dynamic organelles. Indeed, LDs are critical for both lipid metabolism and energy homeostasis. Partial or total PNPLA2 or ABHD5/CGI58 knockdown is characteristic of the cells of NLSD patients; thus, these cells are natural models with which one can unravel LD function. In this review we firstly summarize genetic and clinical data collected from NLSD patients, focusing particularly on muscle, skin, heart, and liver damage due to impaired LD function. Then, we discuss how NLSD cells were used to investigate and expand the current structural and functional knowledge of LDs.

Neutral lipid storage disease with myopathy and dropped head syndrome. Report of a new variant susceptible of treatment with late diagnosis

Neutral lipid storage disease with myopathy (NLSDM) is characterized by the accumulation of cytoplasmic triglyceride droplets in various tissues; this very rare condition is caused by mutations in the PNPLA2 gene, susceptible to specific pharmacological management that decreases clinical progression. We describe the clinical and biochemical characteristics of a Colombian patient with a previously unreported homozygous mutation in the PNPLA2 gene with a difficult to manage disease, who was diagnosed late by advances in molecular techniques.

Novel PNPLA2 gene mutation in a child causing neutral lipid storage disease with myopathy

BackgroundPNPLA2 gene mutations cause neutral lipid storage disease with myopathy (NLSD-M) or cardiomyopathies. The clinical phenotype, blood test results, imaging examination and gene analysis can be used to improve the understanding of NLSD-M, reduce the misdiagnosis rate and prevent physical disability and even premature death.Case presentationWe report a Chinese child with NLSD-M presenting with marked asymmetric skeletal myopathy and hypertrophic cardiomyopathy. Blood biochemical tests revealed increased creatine kinase levels, and echocardiography revealed a diffuse and thick left ventricular wall. Gene analysis revealed a homozygous mutation c.155C > G (p.Thr52Arg) in PNPLA2.ConclusionsAn understanding of the characteristic features is essential for the early diagnosis of NLSD-M. Our data expand the allelic spectrum of PNPLA2 mutations, providing further evidence for genetic and clinical NLSD-M heterogeneity in younger individuals.

F41. Expanding the phenotype-genotype correlations of PNPLA2 mutations

Introduction Neutral lipid storage disease with myopathy (NLSD-M), due to diverse PNPLA2 mutations, usually presents with an asymmetrical weakness, proximal involvement of upper limbs and posterior compartment of lower limbs. NLSD-M can be associated with other co-morbidities, like diabetes mellitus, hyperlipidemia, and most commonly, cardiomyopathy, which can be detected in almost 50% of patients. Although clinical manifestations begin around the third decade, late onset disease with unusual symptoms, such as fatigue and exercise intolerance, has been reported. Magnetic resonance imaging (MRI) of skeletal muscles reveals fatty degeneration, with a predilection for shoulder girdle and lower limb muscles. Electromyographic (EMG) features have been reported in one patient, where complex repetitive discharges (CRD) and myotonic discharges were detected in a few muscles. Methods Description of the clinical, neurophysiological, muscle MRI, pathological and genetic findings of a novel mutation in the PNPLA2 gene. This work received ethics board approval. Results Two sisters (aged 31 years at first examination), born 3 years apart from consanguineous parents, presented with a 2 year history of progressive motor deficits, proximal/asymmetric in upper limbs and distal/symmetric in lower limbs. The most severely affected muscles were: deltoids, biceps, external cuff rotators, gastrocnemius and tibialis anterior muscles. EMG recordings showed diffuse short-duration motor unit potentials, with asymmetrical distribution; some long duration, polyphasic potentials in distal muscles; profuse CRD in the biceps and tibialis anterior and sparse CRD in paravertebral muscles. MRI revealed an asymmetrical fatty replacement in the posterior compartment of thigs and legs, paravertebral musculature, deltoids and biceps. Jordans’ anomaly, characterized by lipid accumulation in leukocytes, was detected in peripheral blood smears in both patients. Muscle biopsy showed cytoplasmic vacuoles, suggestive of neutral lipid accumulation. Genetic analysis revealed a homozygous deletion in exon 6 of PNPLA2 gene (c.995delG), not yet described in the literature. Five years after the initial symptoms, the elder sister was completely dependent for upper limb activities, although she had independent walking, while the younger sister had only minor fine motor skills impairment. Creatine phosphokinase levels increased in a stepwise manner over the years in the elder sister (97–2840 UI/L), while stable levels were found in the younger one (621–681 UI/L). Cardiomyopathy was not present in those patients. Conclusion NLSD-M due to PNPLA2 gene mutations should be suspected in patients presenting with an asymmetrical myopathy with upper limb predominance; profuse and also asymmetrical EMG and MRI abnormalities, even without cardiomyopathy. Although some mutations have been described, genotypical variability seems to be common, so novel mutations should be sought for genetic counselling purposes.

Patients with neutral lipid storage disease with myopathy (NLSDM) in Southwestern China

ObjectivesNeutral lipid storage disease with myopathy (NLSDM) is a rare metabolic myopathy occurring owing to mutations in the patatin like phospholipase domain containing 2 (PNPLA2) gene. Till date, less than 50 patients with PNPLA2 mutations have been reported. In this study, we describe the clinical, pathological, and genetic findings, and muscle magnetic resonance imaging (MRI) changes in four Chinese patients with NLSDM. Patients and methodsPeripheral blood smears were stained using Wright’s stain. Muscle biopsies, muscle MRI, and sequence analysis of PNPLA2 gene were performed. ResultsAll patients exhibited slowly progressive myopathy during adulthood. Cardiomyopathy, sensorineural hearing loss, hepatic adipose infiltration, and hypertriglyceridemia were observed in some patients. Jordan’s anomaly was detected in the blood smears of all patients. Muscle biopsies revealed the presence of massive lipid droplets and rimmed vacuoles in two patients. MR images of the lower lumbar, pelvis, and lower extremities showed the involvement of posterior compartment muscles. The anterior compartment muscles were found to be less affected. Gene analysis for PNPLA2 revealed an identical homozygous mutation c.757 + 1G > T in all patients. ConclusionPatients with NLSDM display clinical heterogeneities despite sharing the same mutation (c.757 + 1G > T) of the PNPLA2 gene, may suggest a founder effect in the region.

Muscle MRI in neutral lipid storage disease (NLSD)

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.

Generation of induced Pluripotent Stem Cells as disease modelling of NLSDM.

Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare defect of triacylglycerol metabolism, characterized by the abnormal storage of neutral lipid in organelles known as lipid droplets (LDs). The main clinical features are progressive myopathy and cardiomyopathy. The onset of NLSDM is caused by autosomal recessive mutations in the PNPLA2 gene, which encodes adipose triglyceride lipase (ATGL). Despite its name, this enzyme is present in a wide variety of cell types and catalyzes the first step in triacylglycerol lipolysis and the release of fatty acids.Here, we report the derivation of NLSDM-induced pluripotent stem cells (NLSDM-iPSCs) from fibroblasts of two patients carrying different PNPLA2 mutations. The first patient was homozygous for the c.541delAC, while the second was homozygous for the c.662G > C mutation in the PNPLA2 gene. We verified that the two types of NLSDM-iPSCs possessed properties of embryonic-like stem cells and could differentiate into the three germ layers in vitro. Immunofluorescence analysis revealed that iPSCs had an abnormal accumulation of triglycerides in LDs, the hallmark of NLSDM. Furthermore, NLSDM-iPSCs were deficient in long chain fatty acid lipolysis, when subjected to a pulse chase experiment with oleic acid. Collectively, these results demonstrate that NLSDM-iPSCs are a promising in vitro model to investigate disease mechanisms and screen drug compounds for NLSDM, a rare disease with few therapeutic options.

Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene

Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene

Hypophagia and metabolic adaptations in mice with defective ATGL-mediated lipolysis cause resistance to HFD-induced obesity

Adipose triglyceride lipase (ATGL) initiates intracellular triglyceride (TG) catabolism. In humans, ATGL deficiency causes neutral lipid storage disease with myopathy (NLSDM) characterized by a systemic TG accumulation. Mice with a genetic deletion of ATGL (AKO) also accumulate TG in many tissues. However, neither NLSDM patients nor AKO mice are exceedingly obese. This phenotype is unexpected considering the importance of the enzyme for TG catabolism in white adipose tissue (WAT). In this study, we identified the counteracting mechanisms that prevent excessive obesity in the absence of ATGL. We used "healthy" AKO mice expressing ATGL exclusively in cardiomyocytes (AKO/cTg) to circumvent the cardiomyopathy and premature lethality observed in AKO mice. AKO/cTg mice were protected from high-fat diet (HFD)-induced obesity despite complete ATGL deficiency in WAT and normal adipocyte differentiation. AKO/cTg mice were highly insulin sensitive under hyperinsulinemic-euglycemic clamp conditions, eliminating insulin insensitivity as a possible protective mechanism. Instead, reduced food intake and altered signaling by peroxisome proliferator-activated receptor-gamma (PPAR-γ) and sterol regulatory element binding protein-1c in WAT accounted for the phenotype. These adaptations led to reduced lipid synthesis and storage in WAT of HFD-fed AKO/cTg mice. Treatment with the PPAR-γ agonist rosiglitazone reversed the phenotype. These results argue for the existence of an adaptive interdependence between lipolysis and lipid synthesis. Pharmacological inhibition of ATGL may prove useful to prevent HFD-induced obesity and insulin resistance.

Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings

Neutral lipid storage disease with myopathy (NLSD-M) is a rare autosomal recessive disorder characterised by an abnormal accumulation of triacylglycerol into cytoplasmic lipid droplets (LDs). NLSD-M patients are mainly affected by progressive myopathy, cardiomyopathy and hepatomegaly. Mutations in the PNPLA2 gene cause variable phenotypes of NLSD-M. PNPLA2 codes for adipose triglyceride lipase (ATGL), an enzyme that hydrolyses fatty acids from triacylglycerol. This report outlines the clinical and genetic findings in a NLSD-M Italian family with three affected members. In our patients, we identified two novel PNPLA2 missense mutations (p.L56R and p.I193F). Functional data analysis demonstrated that these mutations caused the production of ATGL proteins able to bind to LDs, but with decreased lipase activity. The oldest brother, at the age of 38, had weakness and atrophy of the right upper arm and kyphosis. Now he is 61 years old and is unable to raise arms in the horizontal position. The second brother, from the age of 44, had exercise intolerance, cramps and pain in lower limbs. He is currently 50 years old and has an asymmetric distal amyotrophy. One of the two sisters, 58 years old, presents the same PNPLA2 mutations, but she is still oligo-symptomatic on neuromuscular examination with slight triceps muscle involvement. She suffered from diabetes and liver steatosis. This NLSD-M family shows a wide range of intra-familial phenotypic variability in subjects carrying the same mutations, both in terms of target-organs and in terms of rate of disease progression.

Metabolic Consequences of Adipose Triglyceride Lipase Deficiency in Humans: An In Vivo Study in Patients With Neutral Lipid Storage Disease With Myopathy

The role of adipose triglyceride lipase (ATGL) in intermediate substrates metabolism has not been fully elucidated in humans. Our objective was to evaluate the consequences of ATGL deficiency on body fat distribution, insulin sensitivity, fatty acids metabolism, and energy substrate utilization. Body composition and organ fat content were measured by bioimpedance and (1)H nuclear magnetic resonance spectroscopy; heart glucose metabolism by [(18)F]deoxyglucose positron emission tomography and insulin sensitivity and β-cell function by oral glucose tolerance and 2-step euglycemic-hyperinsulinemic clamp. Lipolysis ([(2)H5]glycerol turnover) and indirect calorimetry were evaluated at fasting, after oral glucose load, during the clamp, and also during an iv epinephrine infusion. These metabolic investigations were carried out during hospitalization. Three patients affected by neutral lipid storage disease with myopathy (NLSDM) due to homozygosity for loss-of-function mutations in the ATGL gene and 6 sex-, age-, and body mass index-matched controls were studied. As expected, NLSDM patients showed diffuse, although heterogeneous, fat infiltration in skeletal muscles associated with increased visceral fat. Although heart and liver were variably affected, fat content in the pancreas was increased in all patients. Compared with healthy controls, NLSDM patients showed impaired insulin response to glucose possibly related to the severe pancreatic steatosis, preserved whole-body insulin sensitivity, and a shift toward glucose metabolism in the heart. Fasting nonesterified fatty acid concentrations as well as basal lipolytic rates and the antilipolytic effect of insulin were normal in NLSDM patients, whereas the lipolytic effect of norepinephrine was impaired. Finally, no significant abnormality in the respiratory quotient was noted in NLSDM patients. In humans, ATGL has a remarkable effect on cellular lipid droplet handling, and its lack causes both perivisceral, skeletal muscle, and pancreas fat accumulation; in contrast, the impact on whole-body insulin sensitivity and fatty acid metabolism is minor.

Effects of Bezafibrate Treatment in a Patient and a Carrier With Mutations in the PNPLA2 Gene, Causing Neutral Lipid Storage Disease With Myopathy

Neutral lipid storage disease with myopathy (NLSDM) is a rare but severe genetic disorder characterized by excessive lipid accumulation in tissues including skin, bone marrow, heart, liver, and muscles. Clinically, NLSDM patients present with severe dilated cardiomyopathy, skeletal muscle myopathy, and insulin resistance.1 NLSDM is caused by a defect in the PNPLA2 gene encoding the enzyme adipose triglyceride lipase (ATGL),2 which catalyzes the breakdown of triglycerides in multiple tissues and is the rate-limiting step of lipolysis. Although heterozygous carriers and homozygous patients both present with similar clinical symptoms, the severity of these symptoms in homozygous patients is more dramatic, leading to premature death attributed to dilated cardiomyopathy in some patients.1,2 To date, the only available treatment is strict dietary guidelines and is focused on treating the comorbidities rather than targeting the primary defect. To investigate cardiac lipotoxicity in NLSDM, ATGL-deficient mice have been investigated. Just like NLSDM patients, ATGL-deficient mice are also characterized by excessive lipid storage in skeletal muscle, liver, and heart, and they develop cardiomyopathy at a young age, resulting in premature death.3 Interestingly, we reported recently that a lack of ATGL resulted in a diminished cardiac peroxisome proliferator-activated receptor (PPAR) activity and mitochondrial function, suggesting that lipolysis-derived fatty acids or fatty acid byproducts serve as transcriptional activators of PPARs.4 Subsequently, pharmacological treatment of ATGL-deficient mice with PPAR agonists completely reversed the mitochondrial defects, restored cardiac function, and prevented premature death. These promising findings inspired us to investigate whether PPAR agonist treatment in patients and carriers of a PNPLA2 gene defect could also have beneficial effects. Although NSLDM is a very rare disease, we had the opportunity to study 2 sisters with PNPLA2 gene mutations. Patient 1 is a 37-year-old woman with a body mass index of 21.4 kg/m2. …

A Late-Onset Case of Neutral Lipid Storage Disease with Myopathy,Dropped Head Syndrome, and Peripheral Nerve Involvement

Neutral lipid storage disease with myopathy (NLSDM) is a rare autosomal recessive disorder of neutral lipid metabolism. Clinical manifestations include progressive skeletal myopathy, cardiomyopathy, and liver dysfunction. Clinical severity is variable and additional symptoms may include diabetes mellitus, chronic pancreatitis, hypothyroidism, neurosensory hearing loss, and short stature. We report a 79-year-old man with progressive proximal arm weakness, lipid storage myopathy, dropped head syndrome, and peripheral nervous system involvement. He harboured a novel homozygous missense mutation, c.570A>C (p.S191R) in the patatin-like phospholipase domain containing 2 (PNPLA2) gene, confirming the diagnosis of NLSDM. The S191R mutation causes late-onset NLSDM without cardiac dysfunction. The previously unreported association with dropped head syndrome expands the clinical spectrum of NLSDM.

Neutral lipid storage disease with myopathy: A whole-body nuclear MRI and metabolic study

Neutral lipid storage disease with myopathy (NLSDM) is caused by a mutation in the gene encoding adipose triglyceride lipase (ATGL), and is characterized by the presence of numerous triglyceride-containing cytoplasmic droplets in type I muscle fibers. Major clinical manifestations concern the heart and skeletal muscle, and some patients also present diabetes mellitus. We report the clinical, metabolic, and whole-body nuclear magnetic resonance imaging findings of three patients with NLSDM. Muscle MRI study was consistent with previous descriptions, and allowed to show a common pattern of fatty replacement. Muscle changes predominated in the paravertebral muscles, both compartments of legs, and posterior compartment of the thighs. A more variable distribution of muscle involvement was observed on upper limbs, with marked asymmetry in one patient, and alterations predominating on supra and infra spinatus, biceps brachialis and anterior compartment of arms. Cardiac NMR studies revealed anomalies despite normal echocardiography in two patients. Endocrine studies showed low leptin and adiponectine levels, a moderate increase in insulin levels at fasting state, and even greater increase after oral glucose tolerance test in one patient. Two patients had elevated triglycerides and low cholesterol-HDL. Based on these analyses, regular control of cardiometabolic risks appear mandatory in the clinical follow-up of these subjects.