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1.
Semin Cardiothorac Vasc Anesth ; 23(4): 409-412, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30985242

RESUMO

A 40-year-old male with alcoholic cirrhosis and end-stage renal disease presented for simultaneous liver and kidney transplantation. Hemodialysis was utilized intraoperatively during liver transplantation. During the procedure, the patient developed refractory hypotension and ultimately received hydroxocobalamin for vasoplegia. Shortly after administration, the hemodialysis machine ceased working after a "blood leak" alarm developed. Without the ability to continue intraoperative dialysis, the kidney transplantation portion of his surgery was postponed. The patient was transferred to the intensive care unit, where he underwent continuous renal replacement therapy overnight, and his kidney transplant proceeded the following morning.


Assuntos
Hidroxocobalamina/administração & dosagem , Diálise Renal , Vasoplegia/tratamento farmacológico , Adulto , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Masculino
2.
Clin Med (Lond) ; 19(2): 129-130, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30872294

RESUMO

An 18-year-old female patient presented to the emergency department with non-specific neurological and gastrointestinal symptoms and was found to be pancytopenic. Her vitamin B12 level was low with a normal mean corpuscular volume and her full blood count 2 months previously had been within normal range. She reported heavy use of nitrous oxide over the previous 2 weeks and other investigations revealed no cause for her pancytopenia. Her pancytopenia resolved with discontinuation of nitrous oxide and vitamin B12 treatment. Heavy use of nitrous oxide should be considered as a cause of pancytopenia.


Assuntos
Óxido Nitroso/efeitos adversos , Pancitopenia/etiologia , Deficiência de Vitamina B 12 , Adolescente , Feminino , Humanos , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/uso terapêutico , Deficiência de Vitamina B 12/induzido quimicamente , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/tratamento farmacológico
4.
J Cardiothorac Vasc Anesth ; 33(5): 1301-1307, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30606508

RESUMO

OBJECTIVE: To compare the efficacy of methylene blue with combination therapy with hydroxocobalamin in patients experiencing vasoplegic syndrome after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. PARTICIPANTS: Patients who received methylene blue with or without hydroxocobalamin for refractory vasoplegic syndrome rescue therapy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 0.the ability to maintain mean arterial pressure (MAP) >60 mmHg beyond 1hour after study drug administration. Other pertinent outcomes included MAP at hours 6, 12, and 24 post-administration; both raw and proportional changes of vasopressor doses from baseline at hours 1, 6, 12, and 24 post-administration; and change in pulmonary artery catheter hemodynamics. Overall, 28 doses were administered in 14 patients in the monotherapy group and 17 doses (10 methylene blue, 7 hydroxocobalamin) were administered in 6 patients in the combination therapy group. There were no differences in ability to maintain MAP at 1hour, with 71% of the monotherapy and 82% of combination therapy patients meeting MAP goals (p = 0.49). Pairwise comparisons demonstrated vasopressor reductions at 6, 12, and 24hours in both groups, but only significant reductions at 1hour were observed in the combination therapy group (-0.06 µg/kg/min; p = 0.003) but not in the monotherapy group (-0.015 µg/kg/min; p = 0.14). CONCLUSION: This is the first study to compare methylene blue monotherapy with combination therapy, which suggests there may be an advantage to combination therapy. Further characterization of ideal dosing, timing, and agent selection should be investigated on a larger scale format.


Assuntos
Hidroxocobalamina/administração & dosagem , Azul de Metileno/administração & dosagem , Vasoconstritores/administração & dosagem , Vasoplegia/tratamento farmacológico , Vasoplegia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Vasoplegia/diagnóstico , Complexo Vitamínico B/administração & dosagem
6.
Eur J Nutr ; 58(1): 261-270, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29209773

RESUMO

PURPOSE: We compare the effect of 8-week oral supplementation with cyano-B12 (currently used in vitamin pills) and hydroxo-B12 (predominant form in the diet) in a population with nutritional vitamin B12 deficiency. METHODS: Fifty-one healthy Indian adults with baseline serum cobalamin < 200 pmol/L were supplied for 8 weeks with daily oral supplements of 3-µg cyano-B12 (n = 15), 3-µg hydroxo-B12 (n = 16), or a placebo (n = 20). Blood at baseline, and each following week, was examined for total cobalamin, holotranscobalamin, methylmalonic acid, and homocysteine. RESULTS: The study groups did not differ at baseline and were characterized by [median (range)] serum cobalamin [128 (68-191) pmol/L], holotranscobalamin [16 (6-41) pmol/L], methylmalonic acid [0.8 (0.3-1.7) µmol/L], homocysteine [17.9 (8.5-100.9) µmol/L], and a combined indicator of B12 status 4cB12 of - 1.65 (- 0.64 to - 4.07). The group supplemented with cyano-B12 showed a higher increase in total serum cobalamin than the group treated with hydroxo-B12, while other biomarkers changed comparably in the two groups. After 8 weeks of treatment, the biomarker values of the supplemented groups (pooled) differed significantly from the placebo group. Yet, the vitamin B12 status was still poor [cobalamin: 168 (87-302) pmol/L; holotranscobalamin: 19 (8-45) pmol/L; methylmalonic acid: 0.7 (0.2-1.7) µmol/L; homocysteine: 17.2 (2.6-96.8) µmol/L; 4cB12 = - 1.34 (- 0.33 to - 3.3)]. CONCLUSION: 8-week supplementation with 3-µg cyano-B12 elevated serum cobalamin more than 3 µg hydroxo-B12, but all other biomarkers changed similarly in both groups. Supplementation with 3 µg vitamin B12 did not reverse the low status in individuals with nutritional vitamin B12 deficiency. CLINICAL TRIAL REGISTRY OF INDIA: REF/2017/02/013343.


Assuntos
Suplementos Nutricionais , Hidroxocobalamina/uso terapêutico , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Administração Oral , Adulto , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/sangue , Índia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/sangue , Adulto Jovem
7.
A A Pract ; 12(9): 332-335, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30431443

RESUMO

In this case report, we describe 2 patients with septic shock requiring high-dose vasopressors for hemodynamic support despite aggressive fluid resuscitation. After the administration of high-dose hydroxocobalamin for presumed septic vasoplegic syndrome, both patients had an immediate response to hydroxocobalamin with a rapid and lasting improvement of blood pressure that significantly reduced the need for vasopressor support.


Assuntos
Hidroxocobalamina/administração & dosagem , Choque Séptico/complicações , Vasoplegia/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hidroxocobalamina/farmacologia , Masculino , Pessoa de Meia-Idade , Choque Séptico/tratamento farmacológico , Resultado do Tratamento , Vasoplegia/etiologia
8.
Clin Exp Pharmacol Physiol ; 46(3): 216-225, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30575111

RESUMO

Early, non-clinical studies support the use of hydroxocobalamin to treat sepsis-induced hypotension, but there is no translational, large animal model. The objective of this study was to compare survival in a sepsis model where large swine had endotoxaemia induced with lipopolysaccharide (LPS) and were treated with intravenous hydroxocobalamin (HOC), noradrenaline (NA), or saline. Thirty swine (45-55 kg) were anaesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Hypotension, predefined as 50% of baseline, was induced with LPS. Animals then received HOC, NA, or saline and monitored for 3 hours. The main outcome was survival to the conclusion of the study. Using a power of 80% and an alpha of 0.05, 10 animals were used per group. Secondary outcomes included: mean arterial pressure (MAP), systemic vascular resistance (SVR) and cardiac output (CO) along with several markers of sepsis. No differences were detected between groups at baseline or after hypotension. The survival distributions of the three groups were significantly different with more HOC animals surviving (10/10) compared with NA (8/10) or Saline (5/10) (log-rank P < 0.03). MAP was found to be higher in both the HOC and NA groups and HOC achieved the highest SVR. In this large animal, translational study of an endotoxaemic model of sepsis, hydroxocobalamin improved survival when compared with saline.


Assuntos
Hidroxocobalamina/farmacologia , Hipotensão/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Norepinefrina/farmacologia , Solução Salina/farmacologia , Administração Intravenosa , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Feminino , Gases/sangue , Hemodinâmica/efeitos dos fármacos , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/uso terapêutico , Hipotensão/complicações , Hipotensão/metabolismo , Hipotensão/fisiopatologia , Norepinefrina/administração & dosagem , Norepinefrina/uso terapêutico , Solução Salina/administração & dosagem , Solução Salina/uso terapêutico , Choque Séptico/complicações , Suínos
9.
BMJ Case Rep ; 11(1)2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30567139

RESUMO

A 34-year-old previously well woman presented with a 4-week history of diffuse erythema and crusting of skin affecting all four limbs. Examination revealed erythematous skin plaques associated with ulceration and fissuring affecting sun-exposed areas of all four limbs primarily on the dorsal surfaces, and a body mass index of 17 kg/m2 She was admitted under the infectious diseases unit, and an autoimmune and infective screen was performed which returned unremarkable. Dietetic consultation led to the diagnosis of severe protein-energy malnutrition, consequent to a severely restricted, primarily vegan, diet. Analysis of the patient's reported diet with nutritional software revealed grossly suboptimal caloric intake with risk of inadequacy for most micronutrients, vitamins and minerals, including niacin. Oral thiamine, multivitamin, iron supplementation and vitamin B complex were started, and a single intramuscular vitamin B12 dose was administered. Marked improvement was seen after 6 weeks, with near-complete resolution of skin changes. These findings supported a diagnosis of pellagra.


Assuntos
Micronutrientes/deficiência , Niacina/deficiência , Pelagra/diagnóstico , Pele/patologia , Dieta Vegana/efeitos adversos , Eritema/etiologia , Eritema/patologia , Feminino , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/uso terapêutico , Humanos , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/uso terapêutico , Pelagra/tratamento farmacológico , Pelagra/patologia , Tiamina/administração & dosagem , Tiamina/uso terapêutico , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico
10.
Nutrients ; 10(10)2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30322035

RESUMO

Foods contain natural vitamin B12 forms, such as hydroxo⁻B12 (HO⁻B12), whereas vitamin pills contain the synthetic cyano⁻B12 (CN⁻B12). Recent studies in rats showed different tissue distributions of CN⁻B12 and HO⁻B12 24 h after oral administration. Here, we investigate whether these differences are sustained or leveled out with time in both B12-deplete and -replete rats, thereby assessing if the two forms are equally good at maintaining a normal B12 status. Male Wistar rats were fed diets with low (n = 16) or high (n = 12) B12 content for 17 days. At day 10, the rats received a single oral dose of [57Co]-labeled CN⁻B12 or HO⁻B12 (n = 6 and n = 8, respectively, in each diet group). The rats were sacrificed on day 17 and endogenous B12 and [57Co]⁻B12 were measured in liver, kidney, and plasma. We found that the low-B12 diet introduced a B12-deplete state as judged from medians of endogenous B12 compared to rats on a (high-B12 diet): Plasma (565 (1410) pmol/L), liver (28.2 (33.2) pmol/g), and kidneys (123 (1300) pmol/g). One week after oral administration, the labeled B12 was distributed as follows: HO⁻B12 > CN⁻B12 (liver) and CN⁻B12 > HO⁻B12 (kidneys, plasma). The tissue/plasma ratios showed different equilibriums for labeled CN⁻B12 and HO⁻B12 in the B12-deplete and -replete groups. The equilibrium of endogenous B12 resembled [57Co]CN⁻B12 in replete rats but differed from both [57Co]CN⁻B12 and [57Co]HO⁻B12 in deplete rats. The data suggest long-term differences in tissue utilization of the two B12 forms and warrant further studies concerning the possible benefits of consuming HO⁻B12 instead of CN⁻B12 in oral B12 replacement.


Assuntos
Rim/metabolismo , Fígado/metabolismo , Plasma/metabolismo , Distribuição Tecidual , Deficiência de Vitamina B 12/metabolismo , Vitamina B 12/farmacocinética , Administração Oral , Animais , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/metabolismo , Hidroxocobalamina/farmacocinética , Masculino , Ratos Wistar , Vitamina B 12/administração & dosagem , Vitamina B 12/metabolismo
11.
Ann Biol Clin (Paris) ; 76(2): 179-184, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29623888

RESUMO

High dose of the cobalt atom is toxic for mammals. Hydroxocobalamin is considered safe due to the inclusion of the cobalt atom into the heminic moiety. The tissue distribution of cobalt following repeated doses of either hydroxocobalamin or cobalt chloride was studied in Wistar rats. In both cases, cobalt was administered in equimolar doses daily for an overall period of three weeks. Three groups were designed. In the hydroxocobalamin treated group, ten rats received hydroxocobalamin 17.5 mg by intraperitoneal route daily. In the cobalt-treated group, ten rats received cobalt chloride 3 mg i.p. daily. In the control group, six rats received a daily injection of 0.35 mL isotonic sodium chloride i.p. Cobalt concentrations were measured by Inductively Coupled Plasma Atomic Emission. Ours results showed that in rats having received either hydroxocobalamin or cobalt chloride, the tissue concentrations of cobalt were greater than those in the control group. The present study documented that in naive rats, the repeated administration of high doses of cobalt as hydroxocobalamin leads to tissue concentrations of the atom of cobalt significantly lower than those induced by equimolar doses of cobalt administered as cobalt chloride (p <0.05). We conclude that hydroxocobalamin reduced the tissue distribution of the cobalt atom in comparison with cobalt chloride.


Assuntos
Cobalto/administração & dosagem , Cobalto/farmacocinética , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/farmacocinética , Animais , Cobalto/toxicidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Hidroxocobalamina/toxicidade , Injeções Intraperitoneais , Ratos , Ratos Wistar , Distribuição Tecidual , Testes de Toxicidade Crônica
12.
Am J Transplant ; 18(6): 1552-1555, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29573551

RESUMO

A 66-year-old man with cryptogenic cirrhosis secondary to nonalcoholic steatohepatitis presented for orthotopic liver transplantation. Following organ reperfusion, the patient developed vasoplegic syndrome, with arterial blood pressures of approximately 60-70/30-40 mm Hg (mean arterial pressure [MAP] <45 mm Hg) for >90 minutes. He required high-dose norepinephrine and vasopressin infusions, as well as i.v. bolus doses of norepinephrine and vasopressin to reach a goal MAP> 60 mm Hg. There was minimal response to a 2 mg/kg i.v. bolus of methylene blue. Following the administration of 5 g of i.v.hydroxocobalamin, the patient had a profound improvement in arterial blood pressure, with subsequent discontinuation of the vasopressin infusion and rapid reduction of norepinephrine infusion from 20 to 2 µg/min. While there have been several reports of the efficacy of hydroxocobalamin for vasoplegia after cardiopulmonary bypass, there have been only limited cases of hydroxocobalamin used in liver transplantation, and none with high-dose administration. We present a case of vasoplegic syndrome during liver transplantation that was refractory to high-dose vasopressors and methylene blue but responsive to high-dose i.v. hydroxocobalamin.


Assuntos
Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/uso terapêutico , Transplante de Fígado , Vasoplegia/tratamento farmacológico , Idoso , Humanos , Masculino
13.
J Vet Intern Med ; 32(3): 1033-1040, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29572946

RESUMO

BACKGROUND: Prospective studies on maintenance treatment for Beagles with hereditary selective cobalamin (Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a Cbl-dependent metabolite, seems more helpful to monitor Cbl status as compared with serum Cbl concentrations. OBJECTIVES: To evaluate a standardized Cbl supplementation scheme in Beagles with IGS. We hypothesized that a single parenteral dose of 1 mg hydroxocobalamin (OH-Cbl) would maintain clinical and metabolic remission for up to 2 months. ANIMALS: Six client-owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs. METHODS: Prospective study. Monthly IM OH-Cbl (1 mg) supplementation was done over a median of 9 months (range, 6-13) in 6 dogs, followed by bimonthly (every 2 months) injections in 5 dogs over a median of 6 months (range, 3-10). Health status was assessed by routine clinical examinations at injection time points and owner observations. Voided urine samples were collected immediately before OH-Cbl injections for measurement of MMA-to-creatinine concentrations using a gas-liquid chromatography-tandem mass spectrometry (GC-MS) method. RESULTS: All dogs were clinically healthy while receiving monthly and bimonthly OH-Cbl supplementation. Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine (median, 2.9). Median urinary MMA concentrations did not differ between dogs with IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3-50.4) and bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6-50) injections. CONCLUSIONS AND CLINICAL IMPORTANCE: A maintenance parenteral dose of 1 mg OH-Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing.


Assuntos
Anemia Megaloblástica/veterinária , Doenças do Cão/tratamento farmacológico , Hidroxocobalamina/uso terapêutico , Síndromes de Malabsorção/veterinária , Proteinúria/veterinária , Deficiência de Vitamina B 12/veterinária , Anemia Megaloblástica/tratamento farmacológico , Animais , Creatinina/urina , Cães , Esquema de Medicação/veterinária , Feminino , Hidroxocobalamina/administração & dosagem , Injeções Intramusculares/veterinária , Síndromes de Malabsorção/tratamento farmacológico , Masculino , Ácido Metilmalônico/urina , Estudos Prospectivos , Proteinúria/tratamento farmacológico , Vitamina B 12/sangue , Vitamina B 12/urina , Deficiência de Vitamina B 12/tratamento farmacológico
14.
Eur J Nutr ; 57(8): 2847-2855, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29038891

RESUMO

PURPOSE: To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status. METHODS: We included adults with low (n = 59) and normal (n = 42) cobalamin status and measured the change in serum holotranscobalamin (ΔholoTC) before and after 2 day administration of different doses of cyanocobalamin and hydroxocobalamin (CobaSorb test). In the low status group, the test was performed using a cross-over design with identical doses of both cobalamin forms (1.5, 3, and 6 µg, respectively). In the normal status group, the test was performed with either 3, 6, and 9 µg cyanocobalamin (n = 28), or with 9 µg cyanocobalamin and 9 µg hydroxocobalamin (n = 14). RESULTS: In both groups, median ΔholoTC (pmol/L) was higher after intake of cyanocobalamin compared to (hydroxocobalamin) [low status: 1.5 µg: 19 (6); 3 µg: 23 (7); 6 µg: 30 (14); normal status: 9 µg: 30 (13) pmol/L]. Independent of B12 form, no difference was observed in ΔholoTC between those receiving 1.5 and 3 µg in the low status group or 6 and 9 µg cyanocobalamin in the normal status group. However, in both groups, administration of 6 µg cobalamin resulted in a significant higher ΔholoTC than did 3 µg [low status: p = 0.02 (0.009) for cyanocobalamin (hydroxocobalamin); normal status: p = 0.03 for cyanocobalamin]. CONCLUSIONS: Administration of cyanocobalamin resulted in a more than twofold increase in holoTC in comparison with hydroxocobalamin. The absorptive capacity was reached only by doses above 3 µg cobalamin. Our results underscore the importance of using the same form of cobalamin when comparing uptake under different conditions. CLINICAL TRIAL REGISTRY NUMBER: NCT02832726 at https://clinicaltrials.gov and 2016/09/012147 at Clinical Trials Registry India.


Assuntos
Hidroxocobalamina/administração & dosagem , Transcobalaminas/metabolismo , Vitamina B 12/administração & dosagem , Administração Oral , Adolescente , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina B 12/sangue , Adulto Jovem
15.
Ann Card Anaesth ; 20(4): 462-464, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28994688

RESUMO

Vasoplegic syndrome is a well-recognized complication during cardiopulmonary bypass (CPB) and is associated with increased morbidity and mortality, especially when refractory to conventional vasoconstrictor therapy. This is the first reported case of vasoplegia on CPB unresponsive to methylene blue whereas responsive to hydroxocobalamin, which indicates that the effect of hydroxocobalamin outside of the nitric oxide system is significant or that the two drugs have a synergistic effect in one or multiple mechanisms.


Assuntos
Antídotos/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/métodos , Hematínicos/administração & dosagem , Hematínicos/uso terapêutico , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/uso terapêutico , Azul de Metileno/uso terapêutico , Vasoplegia/tratamento farmacológico , Resistência a Medicamentos , Ecocardiografia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Vasoplegia/diagnóstico por imagem
16.
Mol Genet Metab ; 122(1-2): 60-66, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28693988

RESUMO

INTRODUCTION: Cobalamin C disease is a multisystemic disease with variable manifestations and age of onset. Genotype-phenotype correlations are well-recognized in this disorder. Here, we present a large cohort of individuals with cobalamin C disease, several of whom are heterozygous for the c.482G>A pathogenic variant (p.Arg161Gln). We compared clinical characteristics of individuals with this pathogenic variant to those who do not have this variant. To our knowledge, this study represents the largest single cohort of individuals with the c.482G>A (p.Arg161Gln) pathogenic variant. METHODS: A retrospective chart review of 27 individuals from 21 families with cobalamin C disease who are followed at our facility was conducted. RESULTS: 13 individuals (48%) are compound heterozygous with the c.482G>A (p.Arg161Gln) on one allele and a second pathogenic variant on the other allele. Individuals with the c.482G>A (p.Arg161Gln) pathogenic variant had later onset of symptoms and easier metabolic control. Moreover, they had milder biochemical abnormalities at presentation which likely contributed to the observation that 4 individuals (31%) in this group were missed by newborn screening. CONCLUSION: The c.482G>A (p.Arg161Gln) pathogenic variant is associated with milder disease. These individuals may not receive a timely diagnosis as they may not be identified on newborn screening or because of unrecognized, late onset symptoms. Despite the milder presentation, significant complications can occur, especially if treatment is delayed.


Assuntos
Gerenciamento Clínico , Variação Genética , Homocistinúria/genética , Deficiência de Vitamina B 12/congênito , Adolescente , Adulto , Alelos , Proteínas de Transporte/genética , Criança , Pré-Escolar , Feminino , Seguimentos , Estudos de Associação Genética , Genótipo , Heterozigoto , Homocistinúria/diagnóstico , Homocistinúria/terapia , Humanos , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/uso terapêutico , Lactente , Recém-Nascido , Masculino , Mutação , Triagem Neonatal , Fenótipo , Estudos Retrospectivos , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/genética , Deficiência de Vitamina B 12/terapia , Adulto Jovem
17.
BMJ Case Rep ; 20172017 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-28478387

RESUMO

Severe B12 vitamin deficiency due to diminished dietary intake is a known cause of severe pancytopenia with bleeding diathesis. The authors report a case with sudden-onset bilateral vision loss, severe pancytopenia and multiple organ failure secondary to B12 vitamin deficiency in a patient with a strict vegetarian diet. On funduscopic examination the patient had multiple bilateral exuberant haemorrhages in all retinal layers. Five months after presentation, he had a complete visual recovery without ophthalmological intervention.


Assuntos
Dieta Vegetariana/efeitos adversos , Hidroxocobalamina/uso terapêutico , Desnutrição/diagnóstico , Pancitopenia/tratamento farmacológico , Deficiência de Vitamina B 12/complicações , Adulto , Assistência ao Convalescente , Diagnóstico Diferencial , Comportamento Alimentar/fisiologia , Humanos , Hidroxocobalamina/administração & dosagem , Injeções Intramusculares , Cuidados para Prolongar a Vida/métodos , Masculino , Desnutrição/etiologia , Pancitopenia/etiologia , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/etiologia , Resultado do Tratamento , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Vitamina B 12/sangue , Deficiência de Vitamina B 12/diagnóstico
18.
Eur J Clin Nutr ; 71(8): 1013-1015, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28537576

RESUMO

The vitamin B12 status of infants depends on maternal B12 status during pregnancy, and during lactation if breastfed. We present a 9-month-old girl who was admitted to the metabolic unit for assessment of developmental delay. She was exclusively breastfed and the introduction of solids at 5 months was unsuccessful. Investigations revealed pancytopenia, undetectable B12 and highly elevated methylmalonic acid and homocysteine. Methylmalonic acid and homocysteine normalised following B12 injections. Marked catch-up of developmental milestones was noted after treatment with B12. Investigations of parents showed normal B12 in the father and combined B12 and iron deficiency in the mother. Maternal B12 deficiency, most likely masked by iron deficiency, led to severe B12 deficiency in the infant. Exclusive breastfeeding and a subsequent failure to wean exacerbated the infant's B12 deficiency leading to developmental delay. This case highlights the need for development of guidelines for better assessment of B12 status during pregnancy.


Assuntos
Anemia Ferropriva/diagnóstico , Aleitamento Materno , Diagnóstico Tardio , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Deficiência de Vitamina B 12/diagnóstico , Aborto Habitual/fisiopatologia , Adulto , Anemia Ferropriva/complicações , Anemia Ferropriva/dietoterapia , Anemia Ferropriva/etiologia , Aleitamento Materno/efeitos adversos , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/prevenção & controle , Suplementos Nutricionais , Feminino , Compostos Ferrosos/uso terapêutico , Hematínicos/administração & dosagem , Hematínicos/uso terapêutico , Humanos , Hidroxocobalamina/administração & dosagem , Hidroxocobalamina/uso terapêutico , Lactente , Injeções Intramusculares , Pancitopenia/etiologia , Gravidez , Índice de Gravidade de Doença , Resultado do Tratamento , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/tratamento farmacológico , Deficiência de Vitamina B 12/fisiopatologia
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