Genetic Deficiency of Adipose Triglyceride Lipase Is Associated With a Novel Type of Podocytopathy

Nagasawa, Yasuyuki; Okumura, Takahiro; Hara, Yasuhiro; Kondo, Toru; Hasegawa, Midori; Ikeda, Yoshihiko; Murohara, Toyoaki; Hirano, Ken

doi:10.1016/j.ekir.2021.07.013

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…Then, TGCV was encoded in the Orphanet (ORPHA code: 565612). Excessive TG accumulation in the myocardium and smooth muscle cells results in various complications including heart failure, cardiomyopathy, arrhythmia, coronary artery disease, chronic kidney disease, and skeletal muscle myopathy [12][13][14], all of which determine a poor prognosis. Early phase clinical trials with a novel orphan drug, CNT-01, have been successfully completed in Japan [15].…”

Section: Introductionmentioning

confidence: 99%

Methods of calculating 123I-β-methyl-P-iodophenyl-pentadecanoic acid washout rates in triglyceride deposit cardiomyovasculopathy

et al. 2022

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Objective This study aimed to optimize various methods of calculating washout rates (WRs) of 123I-β-methyl-p-iodophenyl-pentadecanoic (BMIPP), as they are essential to diagnose triglyceride deposit cardiomyovasculopathy (TGCV) which is a rare disease entity identified in Japan and has been encoded in Orphanet (ORPHA code 565612). Methods We calculated WRs of 123I-BMIPP from early (20 min) and delayed (200 min) images. We evaluated six methods of calculating WRs to discriminate TGVC patients (age, 56.8 ± 14.6 y; male, n = 13; female, n = 4) and 21 123I-BMIPP studies were involved including 4 follow-up studies. Washout rates were calculated by two planar methods using anterior images with cardiac and background regions of interest (ROIs) and by four SPECT methods using either array and polar plots or summed short-axis images. The final diagnoses of TGCV were confirmed according to the 2020 diagnostic criteria, and the diagnostic accuracy of WRs calculated using the six methods was analyzed using the area under receiver-operating characteristics curves (ROC-AUC). Multiple scatter-plot matrix methods were evaluated with correlations for comparison. Results All six methods were useful for diagnosis and did not significantly differ. The four SPECT methods showed excellent diagnostic accuracy (AUC 1.0), whereas the planar methods with and without background correction could be acceptable (AUC 0.857 and 0.964, respectively). The WRs were relatively lower for patients with CAD and remarkable metabolic defects than for patients with TGCV but without defects. Conclusions For the diagnosis of TGCV, the WR cutoff of 10% of 123I-BMIPP functioned well in planar and SPECT discrimination based on computational methods as a classifier. However, calculation optimization should improve TGCV diagnoses.

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Section: Introductionmentioning

confidence: 99%

Methods of calculating 123I-β-methyl-P-iodophenyl-pentadecanoic acid washout rates in triglyceride deposit cardiomyovasculopathy

et al. 2022

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“…Defective intracellular lipolysis of TG results in cardiomyocyte steatosis and severe heart failure [ 6 ]. To date, only ten patients have been reported globally [ [3] , [4] , [5] , 7 , 8 ]. Clinically, the patients were diagnosed in middle-age.…”

Section: Introductionmentioning

confidence: 99%

A novel homozygous missense mutation in PNPLA2 in a patient manifesting primary triglyceride deposit cardiomyovasculopathy

Hara

Ikeda

Kimura

et al. 2023

Molecular Genetics and Metabolism Reports

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“…The limitations of the present study are as follows: 1) it would be of interest to know BMIPP-WR in genetic carnitine deficiency, even a pediatric orphan disease; 2) it remains to be investigated prevalence of TGCV among HD patients in larger multi-centered cohorts; 3) the relationship between defective TG lipolysis and cardiorenal systems needs further investigation, as we recently observed that genetic ATGL deficiency can cause a novel type of podocytopathy, in addition to TGCV (20).…”

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confidence: 99%

Carnitine Administration and <sup>123</sup>I-BMIPP Washout Rate in Hemodialysis Patients with Triglyceride Deposit Cardiomyovasculopathy

Hirano,

Kodama,

Miyauchi

et al. 2023

Annals of Nuclear Cardiology

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Triglyceride deposit cardiomyovasculopathy (TGCV) is an emerging rare heart disease with high mortality, characterized by defective intracellular lipolysis of triglycerides (TG). We developed diagnostic criteria for TGCV, in which low washout rate of BMIPP (BMIPP-WR) is a key factor. The working group of the Japan Society of Nuclear Cardiology recently published practice recommendations for measuring BMIPP-WR. We reported that hemodialysis (HD) patients with TGCV exhibited a markedly higher cardiovascular risk than those without TGCV. Secondary carnitine deficiency is common in patients undergoing HD, as carnitine is removed from the circulation. However, clinical evidence linking carnitine levels to BMIPP-WR is limited. Here we report the effect of L-carnitine administration on the BMIPP-WR in 9 chronic HD patients with TGCV in a retrospective cohort. The mean age at TGCV diagnosis was 59 years. Following standard doses of oral Lcarnitine administration, plasma free carnitine levels significantly increased. However, BMIPP-WR was not changed. In normal condition, most BMIPP taken up were esterified/incorporated into TG pool, hydrolyzed by intracellular lipases, and then transported by carnitine shuttle to mitochondria. In TGCV, intracellular TG lipolysis is defective. During the intracellular metabolism of BMIPP, carnitine shuttling occurs downstream of TG lipolysis. Therefore, even when carnitine levels were increased, BMIPP-WR did not change in patients with TGCV who underwent chronic HD. A phase IIb/III clinical trial for TGCV, is underway (jRCT2051210177). Increased awareness of the disease concept of TGCV, along with its diagnostic principles and procedures using BMIPP scintigraphy, is warranted.

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Genetic Deficiency of Adipose Triglyceride Lipase Is Associated With a Novel Type of Podocytopathy

Cited by 4 publications

References 10 publications

Methods of calculating 123I-β-methyl-P-iodophenyl-pentadecanoic acid washout rates in triglyceride deposit cardiomyovasculopathy

Methods of calculating 123I-β-methyl-P-iodophenyl-pentadecanoic acid washout rates in triglyceride deposit cardiomyovasculopathy

A novel homozygous missense mutation in PNPLA2 in a patient manifesting primary triglyceride deposit cardiomyovasculopathy

Carnitine Administration and <sup>123</sup>I-BMIPP Washout Rate in Hemodialysis Patients with Triglyceride Deposit Cardiomyovasculopathy

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