Current Diagnosis and Management of Primary Chylomicronemia
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- Okazaki Hiroaki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
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- Gotoda Takanari
- Department of Metabolic Biochemistry, Faculty of Medicine, Kyorin University
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- Ogura Masatsune
- Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute
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- Ishibashi Shun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Jichi Medical University
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- Inagaki Kyoko
- Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Nippon Medical School
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- Daida Hiroyuki
- Faculty of Health Science, Juntendo University, Juntendo University Graduate School of Medicine
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- Hayashi Toshio
- School of Health Sciences, Nagoya University Graduate School of Medicine
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- Hori Mika
- Department of Endocrinology, Research Institute of Environmental Medicine, Nagoya University
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- Masuda Daisaku
- Department of Cardiology, Health Care Center, Rinku Innovation Center for Wellness Care and Activities (RICWA), Rinku General Medical Center
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- Matsuki Kota
- Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine
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- Yokoyama Shinji
- Institute for Biological Functions, Chubu University
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- Harada-Shiba Mariko
- Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center Research Institute
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Abstract
<p>Primary chylomicronemia (PCM) is a rare and intractable disease characterized by marked accumulation of chylomicrons in plasma. The levels of plasma triglycerides (TGs) typically range from 1,000 - 15,000 mg/dL or higher.</p><p>PCM is caused by defects in the lipoprotein lipase (LPL) pathway due to genetic mutations, autoantibodies, or unidentified causes. The monogenic type is typically inherited as an autosomal recessive trait with loss-of-function mutations in LPL pathway genes (LPL, LMF1, GPIHBP1, APOC2, and APOA5). Secondary/environmental factors (diabetes, alcohol intake, pregnancy, etc.) often exacerbate hypertriglyceridemia (HTG). </p><p>The signs, symptoms, and complications of chylomicronemia include eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, and acute pancreatitis with onset as early as in infancy. Acute pancreatitis can be fatal and recurrent episodes of abdominal pain may lead to dietary fat intolerance and failure to thrive.</p><p>The main goal of treatment is to prevent acute pancreatitis by reducing plasma TG levels to at least less than 500-1,000 mg/dL. However, current TG-lowering medications are generally ineffective for PCM. The only other treatment options are modulation of secondary/environmental factors. Most patients need strict dietary fat restriction, which is often difficult to maintain and likely affects their quality of life.</p><p>Timely diagnosis is critical for the best prognosis with currently available management, but PCM is often misdiagnosed and undertreated. The aim of this review is firstly to summarize the pathogenesis, signs, symptoms, diagnosis, and management of PCM, and secondly to propose simple diagnostic criteria that can be readily translated into general clinical practice to improve the diagnostic rate of PCM. In fact, these criteria are currently used to define eligibility to receive social support from the Japanese government for PCM as a rare and intractable disease.</p><p>Nevertheless, further research to unravel the molecular pathogenesis and develop effective therapeutic modalities is warranted. Nationwide registry research on PCM is currently ongoing in Japan with the aim of better understanding the disease burden as well as the unmet needs of this life-threatening disease with poor therapeutic options.</p>
Journal
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- Journal of Atherosclerosis and Thrombosis
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Journal of Atherosclerosis and Thrombosis 28 (9), 883-904, 2021-09-01
Japan Atherosclerosis Society