neutral lipid storage disease with myopathy

BACKGROUND: Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), also known as Glutaric Aciduria Type II, is an exceptionally rare autosomal recessive genetic disorder that disrupts the metabolism of fatty acids, amino acids, and choline. It presents with a wide range of clinical manifestations, from severe neonatal-onset forms to milder late-onset cases, with symptoms including metabolic disturbances and muscle weakness. Jordan's anomaly is a distinctive morphological feature found in peripheral blood white cells and is typically associated with Neutral Lipid Storage Disease (NLSD)...

The rare disorder known as Neutral Lipid Storage Disease with Myopathy presents with a variety of clinical manifestations, including myopathy, cardiac dysfunction, and other organ complications. Early diagnosis is crucial due to the increased risk of cardiomyopathy. We describe the clinical, histopathological, muscle imaging, and genetic findings of nine neutral lipid storage myopathy patients. Proximal weakness and asymmetric involvement may suggest lipid storage myopathy. While skeletal muscle weakness was the main manifestation in our patients, one case presented only with hyperCKemia...

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...

BACKGROUND: Neutral lipid storage disease with myopathy (NLSD-M) is an autosomal recessive disease that manifests itself around the 3rd to 4th decade with chronic myopathy predominantly proximal in the shoulder girdle. Clinical myotonia is uncommon. We will report a rare case of association of pathogenic variants on PNPLA2 and CLCN1 genes with a mixed phenotype of NLSD-M and a subclinical form of Thomsen's congenital myotonia. CASE PRESENTATION: We describe a patient with chronic proximal myopathy, subtle clinical myotonia and electrical myotonia on electromyography (EMG)...

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Neutral lipid storage disease type M (NLSD-M) is an ultra-rare, autosomal recessive disorder that causes severe skeletal and cardiac muscle damage and lipid accumulation in all body tissues. In this hereditary pathology, the defective action of the adipose triglyceride lipase (ATGL) enzyme induces the enlargement of cytoplasmic lipid droplets and reduction in the detachment of mono- (MG) and diglycerides (DG). Although the pathogenesis of muscle fiber necrosis is unknown, some studies have shown alterations in cellular energy production, probably because MG and DG, the substrates of Krebs cycle, are less available...

Primary triglyceride deposit cardiomyovasculopathy (P-TGCV), caused by a rare genetic mutation in PNPLA2 encoding adipose triglyceride lipase (ATGL), exhibits severe cardiomyocyte steatosis and heart failure. Here, we report the case of a 51-year-old man with P-TGCV homozygous for a novel PNPLA2 mutation (c.446C > G, P149R) in the catalytic domain of ATGL. Analyses of endomyocardial biopsy specimens and in vitro expression experiments showed mutant protein expression with conserved lipid binding, but reduced lipolytic activity, indicating mutation pathogenicity...

Chanarin-Dorfman syndrome (CDS) is a rare, autosomal recessive disorder of impaired triacylglycerol catabolism leading to cytoplasmic deposition of triglycerides in various cell types. We describe the case of an 8-month-old boy with cataracts, strabismus, motor delays, and an ichthyosiform rash since birth. Genetic testing revealed a pathogenic variant of the ABHD5 gene, suggestive of CDS, and further workup demonstrated hepatic steatosis and myopathy. His ichthyosis improved with initiation of a diet low in very long-chain fatty acids and medium-chain fatty acid supplementation...

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BACKGROUND: The lipid storage myopathy (LSM) diagnosis is based on the patient's clinical manifestations and muscle pathology. However, when genetic testing is lacking, there is a high rate of misdiagnosis of the disease. This study aimed to investigate the clinical and pathological features of genetically diagnosed LSM in northern China, analyze genetic mutations' characteristics, and improve the LSM diagnostic rate. METHODS: Twenty patients with LSM diagnosed were collected; meanwhile, the clinical data, muscle samples, and routine pathological staining of muscle specimens were collected...

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...

The diagnostic evaluation of a patient with suspected hereditary muscle disease can be challenging. Clinicians rely largely on clinical history and examination features, with additional serological, electrodiagnostic, radiologic, histopathologic, and genetic investigations assisting in definitive diagnosis. Hematological testing is inexpensive and widely available, but frequently overlooked in the hereditary myopathy evaluation. Hematological abnormalities are infrequently encountered in this setting; however, their presence provides a valuable clue, helps refine the differential diagnosis, tailors further investigation, and assists interpretation of variants of uncertain significance...

ABHD5 protein is widely involved in lipid and energy homeostasis. Mutations in the ABHD5 gene are associated with the onset of Neutral Lipid Storage Disease with Ichthyosis (NLSDI), historically known as Chanarin Dorfman Syndrome (CDS). CDS is a rare autosomal recessive lipid storage disease, characterized by non-bullous congenital ichthyosiform eritrhoderma (NCIE), hepatomegaly and liver steatosis. Myopathy, neurosensory hearing loss, cataracts, nystagmus, strabismus, and mental impairment are considered additional findings...

Lipid myopathies are rare and heterogeneous multi-systemic diseases that may be hereditary or acquired and affect the skeletal muscle [1]. Four types usually demonstrate accumulation of lipids in muscle biopsy specimens that can be visualised using Oil-Red-O (ORO) stain. These comprise (i) Multiple Acyl-CoA Dehydrogenase deficiency (MADD), (ii) Primary Carnitine Deficiency (PCD), (iii) Neutral Lipid Storage Disease with Ichthyosis (NLSDI), and (iv) Neutral Lipid Storage Disease with myopathy (NLSDM) [2]. MADD is an autosomal recessive disorder of fatty acid oxidation with early-onset during the neonatal period or late-onset during child- or adulthood [3]...

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...

Neutral lipid storage disease with myopathy is an ultra-rare, inherited autosomal recessive neuromuscular metabolic disorder caused by pathogenic variants in PNPLA2. It typically presents in adults as a progressive myopathy and is associated with myocardiopathy, hepatic involvement, and high creatine kinase levels. Only three children and adolescents with neutral lipid storage disease with myopathy have been reported. We report a female infant with congenital hypotonia born to consanguineous parents, whose mother presented with polyhydramnios during pregnancy...

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Mutations in the PNPLA2 gene cause neutral lipid storage disease with myopathy (NLSDM) or triglyceride deposit cardiomyovasculopathy. We report a detailed case study of a 53-year-old man with NLSDM. The PNPLA2 gene was analyzed according to the reported method. We summarized the clinical, laboratory, and genetic information of 56 patients, including our patient and 55 other reported patients with homozygous or compound heterozygous mutations in the PNPLA2 gene. We found a novel homozygous mutation (c.194delC) in the PNPLA2 gene that resulted in frameshift...

NLSDM is a rare metabolic myopathy caused by mutations in the patatin-like phosphatase domain protein 2 (PAPLA2) genes. In the present study, we describe the clinical and genetic findings in our Chinese patient with NLSDM. Sequence analysis of PNPLA2 gene was performed. Gene analysis for PNPLA2 revealed an identical homozygous mutation c.757+1G>T in our patient. The clinical symptoms of our patient are related to the type of mutation in the PNPLA2 gene and environmental effects.

INTRODUCTION: Neutral lipid storage disease with myopathy (NLSDM) is a rare lipid metabolism disorder. In this study we evaluated some circulating miRNAs levels in serum samples and the MRI of three affected siblings. METHODS: Three members of one NLSDM family were identified: two brothers and one sister. Muscles of lower and right upper extremities were studied by MRI. Expression profile of miRNAs, obtained from serum samples, was detected using qRT-PCR. RESULTS: Two brothers presented with progressive skeletal myopathy, while the sister had severe hepatosteatosis and diabetes...