Subclinical myopathy in a child with neutral lipid storage disease and mutations in the PNPLA2 gene

Brisca, Giacomo; Cassandrini, Denise; Scapolan, Sara; Astrea, Guja; Valle, Maura; Scuderi, Francesca; Trucco, Federica; Natali, Andrea; Magnano, Gianmichele; Gazzerro, Elisabetta; Minetti, Carlo; Arca, Marcello; Santorelli, Filippo M.; Bruno, Claudio

doi:10.1016/j.bbrc.2012.10.127

Cited by 31 publications

(31 citation statements)

References 19 publications

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“…Unlike leukocytes, in which the proportion of lipids correlates with the severity of the disease, muscle lipid accumulation does not always correlate with the motor impairment. Indeed, as reported previously by other authors [12, 26, 27], we had patients (XI, XII.1, XII.2), with high lipid storage in muscle who were asymptomatic. Only one of our patients (IV.1), who did not have a significant accumulation of lipids in muscle, displayed EMG abnormalities, mild hyperCKemia, weakness and fatigability in the absence of atrophy.…”

Section: Discussionmentioning

confidence: 67%

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Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Pennisi

Arca

Bertini

et al. 2017

Orphanet J Rare Dis

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BackgroundA small number of patients affected by Neutral Lipid Storage Diseases (NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been described in various ethnic groups worldwide. However, relatively little is known about the progression and phenotypic variability of the disease in large specific populations. The aim of our study was to assess the natural history, disability and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one patients who satisfied the criteria for NLSDs were enrolled in a retrospective cross-sectional study to evaluate the genetic aspects, clinical signs at onset, disability progression and comorbidities associated with this group of diseases.ResultsDuring the clinical follow-up (range: 2–44 years, median: 17.8 years), two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five (24%) lost their ability to walk or needed help when walking after a mean period of 30.6 years of disease. None of the patients required mechanical ventilation. No patient required a heart transplant, one patient with NLSD-M was implanted with a cardioverter defibrillator for severe arrhythmias.ConclusionThe genotype/phenotype correlation analysis in our population showed that the same gene mutations were associated with a varying clinical onset and course. This study highlights peculiar aspects of Italian NLSD patients that differ from those observed in Japanese patients, who were found to be affected by a marked hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same mutations, it is conceivable that some additional genetic or epigenetic factors affect the symptoms and progression in this group of diseases.

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Section: Discussionmentioning

confidence: 67%

“…All homozygous patients were born from consanguineous parents. We identified 10 different mutations in 15 NLSD-M patients [5, 7–12], 5 of whom were homozygous and 10 heterozygous.…”

Section: Resultsmentioning

confidence: 99%

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Pennisi

Arca

Bertini

et al. 2017

Orphanet J Rare Dis

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“…All patients (10 NLSD-M and 2 NLSD-I) had genetically confirmed recessive mutations (5 homozygotes and 5 compound heterozygotes for PNPLA2 mutation, and 2 homozygotes for ABDH5 mutations). Complete clinical data of patients has been previously reported [3,[18][19][20][21][22][23][24]. Briefly, NLSD-M patients showed a mild-to-severe muscle weakness and both NLSD-I patients had no skeletal muscle manifestations.…”

Section: Patientsmentioning

confidence: 98%

Muscle MRI in neutral lipid storage disease (NLSD)

Garibaldi

Tasca

Díaz‐Manera

et al. 2016

Neuromuscular Disorders

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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.In the original publication of this article, unfortunately, first word in the title was deleted; this error has now been corrected. Electronic supplementary materialThe online version of this article

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“…Myopathy is often subclinical at an early stage and may be detected or suspected only upon creatine-kinase (CK) screening, needle electromyography or muscle biopsy at this stage [7]. Were the three other females with LVHT or other family members seen by a myologist?…”

Section: Letter To the Editormentioning

confidence: 99%