Current Diagnosis and Management of Abetalipoproteinemia.

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.

Hemolysis Is Responsible for Elevation of Serum Iron Concentration After Regular Exercises in Judo Athletes.

Serum iron concentration increases in marathon athletes after running due to mechanical destruction of red blood cells (hemolysis). This study was performed to examine whether serum iron concentration increases after regular Judo exercise, and if so, whether such post-exercise iron increase is caused by hemolysis. We examined biochemical parameters related to red blood cell and iron metabolism in 16 male competitive Judo athletes before and after traditional exercise training composed of basic movements and freestyle matchup. The parameters were adjusted for changes in plasma volume based on simultaneously measured albumin concentration. The red blood cell count, hemoglobin concentration, and hematocrit levels decreased significantly, by 6.0-8.4%, after Judo exercise. The serum iron concentration and transferrin saturation increased significantly, from 87 ± 34 µg/dL to 98 ± 29 µg/dL and from 27.1 ± 9.7% to 31.2 ± 9.0%, respectively. Furthermore, the serum free hemoglobin level increased by 33.9% (p < 0.05), and haptoglobin concentration decreased by 19.2% (p < 0.001). A significant negative correlation was observed between Δ haptoglobin concentration and Δ serum iron concentration (r = - 0.551, p = 0.027). The results of this study indicate that serum iron concentration increases significantly after Judo exercise due to hemolysis.

Treatment with medium chain fatty acids milk of CD36-deficient preschool children.

OBJECTIVE: CD36 deficiency is characterized by limited cellular long chain fatty acid uptake in the skeletal and cardiac muscles and often causes energy crisis in these muscles. However, suitable treatment for CD36 deficiency remains to be established. The aim of this study was to evaluate the clinical and metabolic effects of medium chain triacylglycerols (MCTs) in two CD36-deficient preschool children who often developed fasting hypoglycemia and exercise-induced myalgia. METHODS: Fasting blood glucose, total ketone bodies, and free fatty acids were examined and compared for usual supper diets and for diets with replacement of one component with 2 g/kg of 9% MCT-containing milk (MCT milk). Changes in serum creatine kinase and alanine aminotransferase levels, resulting from replacement of glucose water intake with 1 g/kg of MCT milk and determined by using bicycle pedaling tasks, were examined and compared. Hypoglycemic and/or myalgia episodes in daily life were also investigated. RESULTS: Biochemically, participants' blood glucose and total ketone bodies levels after overnight fasting substantially increased after dietary suppers containing MCT milk. Increases in serum creatine kinase and alanine aminotransferase levels resulting from the bicycle pedaling task were suppressed by MCT milk. Hypoglycemia leading to unconsciousness and tachycardia before breakfast decreased after introduction of dietary suppers containing MCT milk. Occurrence of myalgia in the lower limbs also decreased after intakes of MCT milk before long and/or strenuous exercising. CONCLUSION: Our results suggest that MCTs can prevent fasting hypoglycemia and exercise-induced myalgia in CD36-deficient young children.

Tape-cast and sintered ß-tricalcium phosphate laminates for biomedical applications: Effect of milled Al2O3 fiber additives on microstructural and mechanical properties.

The aim of this study was to develop the tape-cast, laminated, and sintered ß-tricalcium phosphate (ß-TCP) with milled Al(2)O(3) fibers for biomedical applications. Moreover, the effects of Al(2)O(3)-fiber content on the microstructural and mechanical properties of the sintered ß-TCP laminates were investigated. The milled Al(2)O(3) fibers were added at four different contents, namely 0, 5, 10, or 15 mass%, to the initial ß-TCP slurry. Next, ß-TCP green sheets were fabricated from the ß-TCP slurry containing the milled Al(2)O(3) fibers by a tape-casting method. Finally, six plies of ß-TCP monolayer sheet were laminated and sintered at a maximum temperature of 1100°C in a furnace. The results showed that there were large differences between the apparent porosities, dynamic hardness, and flexural properties of the sintered ß-TCP laminates with Al(2)O(3)-fiber contents of 0 and 5 mass%, but few differences among laminates with fiber contents of 5, 10, and 15 mass%. This indicates that the addition of only 5 mass% of Al(2)O(3) fibers strongly affects the degree of sintering, corresponding to crystallization of the ß-TCP matrix phase. Furthermore, the flexural moduli of our materials ranged from 10.7 to 16.0 GPa when the Al(2)O(3)-fiber content changed from 5 to 15 mass% and were the almost same as those of human bones reported by other researchers. In conclusion, sintered ß-TCP laminates with Al(2)O(3) fibers have potential uses in a wide range of biomedical applications because the microstructural and mechanical properties of the sintered ß-TCP laminates can be controlled by adding Al(2)O(3) fibers to the ß-TCP.