- Single cell analyses demonstrate that a heme - GATA1 feedback loop regulates red cell differentiation. [Journal Article]
- BloodBlood 2018 Dec 10
- Erythropoiesis is the complex, dynamic, and tightly-regulated process that generates all mature red blood cells. To understand this process, we mapped the developmental trajectories of progenitors fr...
Erythropoiesis is the complex, dynamic, and tightly-regulated process that generates all mature red blood cells. To understand this process, we mapped the developmental trajectories of progenitors from wildtype, erythropoietin-treated and Flvcr1-deleted mice at single cell resolution. Importantly, we linked the quantity of each cell's surface proteins to its total transcriptome, which is a novel method. Deletion of Flvcr1 results in high levels of intracellular heme, allowing us to identify heme-regulated circuitry. Our studies demonstrate that in early erythroid cells (CD71+Ter119neg-lo), heme increases ribosomal protein transcripts; suggesting that heme, in addition to upregulating globin transcription and translation, guarantees ample ribosomes for globin synthesis. In later erythroid cells (CD71+Ter119lo-hi), heme decreases GATA1, GATA1-target gene, and mitotic spindle gene expression. These changes occur quickly. For example, in confirmatory studies using human marrow erythroid cells, ribosomal protein transcripts and proteins increase, and GATA1 transcript and protein decrease, within 15-30 minutes of amplifying endogenous heme synthesis with ALA. Since GATA1 initiates heme synthesis, GATA1 and heme together direct red cell maturation, and heme stops GATA1 synthesis, our observations reveal a GATA1-heme autoregulatory loop and implicate GATA1 and heme as the co-master regulators of the normal erythroid differentiation program. In addition, since excessive heme could amplify ribosomal protein imbalance, prematurely lower GATA1 and impede mitosis, these data may help explain the ineffective (early termination of) erythropoiesis in Diamond Blackfan anemia and del(5q) myelodysplasia, disorders with excessive heme in CFU-E/proerythroblasts; explain why these anemias are macrocytic; and show why children with GATA1 mutations have DBA-like clinical phenotypes.
- AA amyloidosis associated with morbid obesity (clinical case). [Journal Article]
- RCReumatol Clin 2018 Dec 04
- We present the case of a 45-year-old woman who was hospitalized due to severe macrocytic anemia and renal failure. The patient presented a morbid obesity. The immunological study showed anti-ENA anti...
We present the case of a 45-year-old woman who was hospitalized due to severe macrocytic anemia and renal failure. The patient presented a morbid obesity. The immunological study showed anti-ENA anti-SSA (Ro52) positive, with negative antinuclear antibodies. Also in the proteinogram (serum immunofixation) the presence of monoclonal bands IgG lambda and IgG kappa, monoclonal component 7.2% (4.68g/L), with elevation of free light chains (kappa 95.94mg/L (3.3-19.4), evidenced, lambda 145.17mg/L (5.71-26.3)). The bone marrow study showed an infiltration of 5% of plasma cells and positive for AA amyloid. Finally, a percutaneous renal biopsy was performed, which again showed amyloid infiltration. In the genetic study, 2 mutations of the family Mediterranean fever gene (MEFV) have been identified. Secondary AA amyloidosis has been described associated with obesity, in addition to a percentage of cases of unknown etiology.
- Arrhythmia in thiamine responsive megaloblastic anemia syndrome. [Journal Article]
- TJTurk J Pediatr 2018; 60(3):348-351
- Argun M, Baykan A, Hatipoğlu N, Akın L, Şahin Y, Narin N, Kurtoğlu S. Arrhythmia in thiamine responsive megaloblastic anemia syndrome. Turk J Pediatr 2018; 60: 348-351. Thiamine responsive megaloblas...
Argun M, Baykan A, Hatipoğlu N, Akın L, Şahin Y, Narin N, Kurtoğlu S. Arrhythmia in thiamine responsive megaloblastic anemia syndrome. Turk J Pediatr 2018; 60: 348-351. Thiamine responsive megaloblastic anemia syndrome (TRMAS) is a rare, autosomal recessive disorder characterized by megaloblastic anemia, diabetes mellitus, and progressive sensorineural deafness. Mutations in the SLC19A2 gene that codes for thiamine transporter 1 protein cause TRMAS, and more than 30 homozygous mutations have been identified to date. Congenital heart diseases and arrhythmias have been reported in few patients. We present cardiac features of five patients with TRMAS. Five patients had macrocytic anemia, diabetes mellitus, and sensorineural deafness. Two siblings had also optic atrophy. SLC19A2 gene mutation was shown in all patients. Two patients developed supraventricular tachycardia during an episode of diabetic ketoacidosis. Five patients had absent P waves on baseline electrocardiography, and one patient had additional low QRS voltage. None of the patients had structural heart disease. Discontinuation of thiamine treatment appears to trigger supraventricular tachycardia episodes at puberty.
- Relationship between cobalamin and folate deficiencies and anemia in dogs. [Journal Article]
- JVJ Vet Intern Med 2018 Nov 29
- CONCLUSIONS: The association between cobalamin and folate deficiencies and macrocytic, nonregenerative anemia established in humans is not routinely present in dogs.
- Prevalence, morphological characterization, and associated factors of anemia among children below 5 years of age attending St. Mary's Hospital Lacor, Gulu District, Northern Uganda. [Journal Article]
- JBJ Blood Med 2018; 9:195-201
- CONCLUSIONS: We report the high prevalence of anemia among children below 5 years of age in Gulu District, Northern Uganda. Thus, strategies geared at addressing the etiologic causes (such as, nutrient deficiency and parasitic infections) are key to reduce it in the region.
- A descriptive study of clinico-hematological profile of megaloblastic anemia in a tertiary care hospital. [Journal Article]
- MJMed J Armed Forces India 2018; 74(4):365-370
- CONCLUSIONS: MA is one of common causes of pancytopenia and severe anemia. Diet plays an important role in causation of MA in vegetarians. An alternative etiology is however, more likely to be found in patients on mixed diet. While overt neurological abnormalities are common in MA, subclinical neuropathy is uncommon.
- Macrocytic anemia is associated with the severity of liver impairment in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective cross-sectional study. [Journal Article]
- BGBMC Gastroenterol 2018 Nov 01; 18(1):161
- CONCLUSIONS: Macrocytic anemia was found to be associated with the severity of liver impairment and might be a predictor for short-term mortality in patients with HBV-related decompensated cirrhosis.
- Psychomotor regression due to vitamin B12 deficiency. [Case Reports]
- PAPan Afr Med J 2018; 30:152
- A vitamin B12 deficiency in infants is rare, but may sometimes be seen in breastfed babies of strict vegetarian mothers. Vitamin B12, also known as cobalamin, is only found in meat and other animal p...
A vitamin B12 deficiency in infants is rare, but may sometimes be seen in breastfed babies of strict vegetarian mothers. Vitamin B12, also known as cobalamin, is only found in meat and other animal products. Most babies have a sufficient supply as long as the mother was not deficient herself. Symptoms and signs of vitamin B12 deficiency appear between the ages of 2 to 12 months and include vomiting, lethargy, failure to thrive, hypotonia, and arrest or regression of developmental skills. Urinary concentrations of methylmalonic acid and homocystine are characteristically elevated in vitamin B12 deficiency. Early treatment for a vitamin B12 deficiency in an infant involves immediate administration of vitamin B12 to the baby and the breastfeeding mother. The infant and mother will each receive an injection of vitamin B12 containing 1,000 mcg or more of the vitamin, and the mother will continue to receive injections every month to raise her own stores. After the initial injection, the baby will often receive future vitamin B12 through food sources. We present a case of vitamin B12 deficiency in a 9-month-old girl presented with psychomotor regression, hypotonia and lethargy. The child was exclusively breast-fed from birth by a mother who was on strict vegetarian diet and belong to a low socio-economic status. Laboratory data revealed bicytopenia with macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The Brain CT revealed a cerebral atrophy and delayed myelination. Vitamin B12 supply was effective on anaemia and psychomotor delay. This case figures out the importance of an early diagnosis in front of psychomoteur regression and hypotonia, given the risk of incomplete neurologic recovery due to vitamin B12 deficiency mainly in the setting of maternal nutritional deficiency.
- Prevalence of low folate deficiency after wheat flour supplementation - should we still measure serum folate? [Journal Article]
- HTHematol Transfus Cell Ther 2018 Oct-Dec; 40(4):305-309
- CONCLUSIONS: In the studied population, the prevalence of serum folic acid deficiency after folate supplementation was low at 1.73%. There was a significant decrease in folate deficiency after folate was added to wheat flour. Given the low prevalence of folic acid deficiency observed in this and similar studies, and the observed change with supplementation, we conclude that routine measurement of serum folate is of limited clinical use.
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- Comprehensive Laboratory Analysis of Korean Acute Alcoholic Intoxication Patients Reveals the Need for a National Hepatitis B Virus Vaccination Program in Korea. [Journal Article]
- KJKorean J Fam Med 2018; 39(6):360-363
- CONCLUSIONS: Patients with AAIP who were transferred to ED had various laboratory abnormalities (anemia, thrombocytopenia, high HbA1c). They had low positive rate of anti-HBs Ab. This might be a public health problem, suggesting the need of hepatitis B virus vaccination program for AAIP. Our data suggest the need of further nationwide studies.