scholarly journals The vitamin B12 processing enzyme, mmachc, is essential for zebrafish survival, growth and retinal morphology

2020 ◽  
Vol 29 (13) ◽  
pp. 2109-2123 ◽  
Author(s):  
Jennifer L Sloan ◽  
Nathan P Achilly ◽  
Madeline L Arnold ◽  
Jerrel L Catlett ◽  
Trevor Blake ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Cholesterol Metabolism ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Methylmalonic Acidemia ◽  
Fluorescent Reporters ◽  
Early Embryonic Lethality ◽  
Full Complement ◽  
Human Disorder ◽  
Cobalamin Metabolism

Abstract Cobalamin C (cblC) deficiency, the most common inborn error of intracellular cobalamin metabolism, is caused by mutations in MMACHC, a gene responsible for the processing and intracellular trafficking of vitamin B12. This recessive disorder is characterized by a failure to metabolize cobalamin into adenosyl- and methylcobalamin, which results in the biochemical perturbations of methylmalonic acidemia, hyperhomocysteinemia and hypomethioninemia caused by the impaired activity of the downstream enzymes, methylmalonyl-CoA mutase and methionine synthase. Cobalamin C deficiency can be accompanied by a wide spectrum of clinical manifestations, including progressive blindness, and, in mice, manifests with very early embryonic lethality. Because zebrafish harbor a full complement of cobalamin metabolic enzymes, we used genome editing to study the loss of mmachc function and to develop the first viable animal model of cblC deficiency. mmachc mutants survived the embryonic period but perished in early juvenile life. The mutants displayed the metabolic and clinical features of cblC deficiency including methylmalonic acidemia, severe growth retardation and lethality. Morphologic and metabolic parameters improved when the mutants were raised in water supplemented with small molecules used to treat patients, including hydroxocobalamin, methylcobalamin, methionine and betaine. Furthermore, mmachc mutants bred to express rod and/or cone fluorescent reporters, manifested a retinopathy and thin optic nerves (ON). Expression analysis using whole eye mRNA revealed the dysregulation of genes involved in phototransduction and cholesterol metabolism. Zebrafish with mmachc deficiency recapitulate the several of the phenotypic and biochemical features of the human disorder, including ocular pathology, and show a response to established treatments.

scholarly journals Proteinuria as a presenting sign of combined methylmalonic acidemia and homocysteinemia: case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ru-Yue Chen ◽  
Xiao-Zhong Li ◽  
Qiang Lin ◽  
Yun Zhu ◽  
Yun-Yan Shen ◽  
...  
Keyword(s):  
Organic Acids ◽  
Vitamin B12 ◽  
Metabolic Diseases ◽  
Methylmalonic Acid ◽  
Clinical Manifestations ◽  
Methylmalonic Aciduria ◽  
Methylmalonic Acidemia ◽  
Initial Presentation ◽  
Gas Chromatography Mass Spectrometry ◽  
Persistent Proteinuria

Abstract Background Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. Case presentation Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography–mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. Conclusions Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals Mild Clinical Presentation of Joubert Syndrome in a Male Adult Carrying Biallelic MKS1 Truncating Variants

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1218
Author(s):  
Raffaella Brunetti-Pierri ◽  
Marianthi Karali ◽  
Francesco Testa ◽  
Gerarda Cappuccio ◽  
Maria Elena Onore ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
Joubert Syndrome ◽  
Male Adult ◽  
Full Field ◽  
Pathogenic Variants ◽  
Disease Spectrum ◽  
Male Individual ◽  
The Central Nervous System

Pathogenic variants in the MKS1 gene are responsible for a ciliopathy with a wide spectrum of clinical manifestations ranging from Meckel and Joubert syndrome (JBTS) to Bardet-Biedl syndrome, and involving the central nervous system, liver, kidney, skeleton, and retina. We report a 39-year-old male individual presenting with isolated Retinitis Pigmentosa (RP), as assessed by full ophthalmological evaluation including Best-Corrected Visual Acuity measurements, fundus examination, Goldmann Visual Field test, and full-field Electroretinography. A clinical exome identified biallelic nonsense variants in MKS1 that prompted post-genotyping investigations for systemic abnormalities of ciliopathy. Brain magnetic resonance imaging revealed malformations of the posterior cranial fossa with the ‘molar tooth sign’ and cerebellar folia dysplasia, which are both distinctive features of JBTS. No other organ or skeletal abnormalities were detected. This case illustrates the power of clinical exome for the identification of the mildest forms of a disease spectrum, such as a mild JBTS with RP in the presented case of an individual carrying biallelic truncating variants in MKS1.

Cirrhosis and Complications of Portal Hypertension

2018 ◽  
Author(s):  
Andres Cardenas ◽  
Isabel Graupera ◽  
Elsa Sola ◽  
Pere Ginès
Keyword(s):  
Liver Transplantation ◽  
Portal Hypertension ◽  
Variceal Bleeding ◽  
Bacterial Infections ◽  
Hepatorenal Syndrome ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Diagnostic Methods ◽  
Decompensated Cirrhosis ◽  
Ultrasound Images

Cirrhosis is the most advanced stage of all the different types of chronic liver diseases. It is defined as a diffuse disorganization of normal hepatic structure by extensive fibrosis associated with regenerative nodules. Hepatic fibrosis is potentially reversible if the causative agent is removed. However, advanced cirrhosis leads to major alterations in the hepatic vascular bed and is usually irreversible. Cirrhosis is a progressive and severe clinical condition associated with considerable morbidity and high mortality. It leads to a wide spectrum of characteristic clinical manifestations, mainly attributable to hepatic insufficiency and portal hypertension. Major complications of portal hypertension include ascites, gastrointestinal (GI) variceal bleeding, hepatic encephalopathy (HE), renal failure, and bacterial infections. In recent years, major advances in the understanding of the natural history and pathophysiology of cirrhosis and the treatment of its complications have led to improved management, quality of life, and life expectancy of patients with this disease. Cirrhosis is also a risk factor for developing hepatocellular carcinoma (HCC). Decompensated cirrhosis carries a poor short-term prognosis; thus, orthotopic liver transplantation (OLT) should always be considered in suitable candidates. This chapter describes the epidemiology, etiology and genetic factors, pathogenesis, diagnosis, general management, and treatment of cirrhosis. Complications of cirrhosis are discussed, including ascites, spontaneous bacterial peritonitis, dilutional hyponatremia, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome and postpulmonary hypertension, HE, and HCC. Indications and contraindications for liver transplantation are described. Figures show liver biopsy results and ultrasound images in cirrhosis from hepatitis C, a patient with tense ascites, transjugular intrahepatic portosystemic shunting (TIPS), large esophageal varices with red spots, and HCC. Tables outline the main causes of cirrhosis and the diagnostic methods for identifying them, the Child-Pugh score, diagnostic criteria for hepatorenal syndrome, grades of HE, and indications for liver transplantation.This chapter contains 6 highly rendered figures, 8 tables, 73 references.

scholarly journals Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders

2018 ◽  
Vol 7 (10) ◽  
pp. 304 ◽  
Author(s):  
Emmanuel Andrès ◽  
Abrar-Ahmad Zulfiqar ◽  
Khalid Serraj ◽  
Thomas Vogel ◽  
Georges Kaltenbach
Keyword(s):  
Vitamin B12 ◽  
Prospective Studies ◽  
Clinical Manifestations ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
Cochrane Library ◽  
Clinical Approach ◽  
Oral Vitamin ◽  
Hand Search ◽  
B12 Deficiency

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 2018, and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption (n = 6), Biermer’s disease (n = 3), veganism or vegetarianism (n = 1), total gastrectomy after Roux-en-Y gastric bypass (n = 2) and Crohn’s disease (n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.

Status of Vitamin B12 and Folate among the Urban Adult Population in South India

2015 ◽  
Vol 68 (2) ◽  
pp. 94-102 ◽  
Author(s):  
M. Sivaprasad ◽  
T. Shalini ◽  
N. Balakrishna ◽  
M. Sudarshan ◽  
P. Lopamudra ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Vitamin B12 ◽  
Wide Spectrum ◽  
Adult Population ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Healthy Adults ◽  
Significant Difference ◽  
B12 Deficiency ◽  
Apparently Healthy

Background: Deficiency of vitamin B12 (B12) and folate (FA) leads to a wide spectrum of disorders that affect all age groups. However, reports on B12 and FA status in healthy adults in India are limited. Hence, we determined the plasma levels and dietary intake of B12 and FA in the adult population. Methods: We conducted a community-based cross-sectional study in an urban setup among 630 apparently healthy adults distributed into 3 age groups: 21-40, 41-60 and >60 years. Plasma concentrations of B12 and FA were analyzed by radio immunoassay and dietary intake by 24-hour recall method. Results: The overall prevalence of FA deficiency was 12%, but there was no significant difference in plasma FA concentrations among the groups. While the overall prevalence of B12 deficiency was 35%, it was significantly higher in the 21-40 (44%) and 41-60 age groups (40%) when compared with the >60 group (30%). B12 deficiency was higher in vegetarians (54%) compared to those consuming mixed diet (31%), and the reverse was the case with FA. However, the dietary intakes of FA and B12 were not significantly different among the groups. Conclusions: These results indicate a higher prevalence of B12 deficiency in apparently healthy adults in an urban setup.

scholarly journals 858 ORAL TREATMENT OF INHERITED VITAMIN B12-RESPONSIVE METHYLMALONIC ACIDEMIA (MMA)

1985 ◽  
Vol 19 (4) ◽  
pp. 253A-253A
Author(s):  
Flemming Skovby ◽  
John Harper ◽  
Maurice J Mahoney
Keyword(s):  
Vitamin B12 ◽  
Oral Treatment ◽  
Methylmalonic Acidemia

scholarly journals PROVIRAL LOAD OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE 1 (HTLV-1) AND COMORBIDITIES IN ASSYMPTOMATIC CARRIERS

2013 ◽  
Vol 1 (2) ◽  
Author(s):  
Raonne Souza Almeida Alves Menezes ◽  
Bernardo Galvão Castro Filho ◽  
Maria Fernanda Rios Grassi
Keyword(s):  
T Cell ◽  
Urinary Retention ◽  
Medical Records ◽  
Proviral Load ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Human T Cell ◽  
High Proviral Load ◽  
Infected Cells

This study aimed to describe comorbidities and symptoms of asymptomatic HTLV-1-infected patients according to the proviral load. Medical records were revised and patients categorized in high and low proviral load groups: >5% and <5% -infected cells, respectively. Frequency of symptoms was quantified. A total of 64 patients were evaluated. Twenty three (36%) patients had high proviral load. All patients had clinical abnormalities reported in the medical records. The most frequently comorbidities were hypertension (37.5%) and depression (25%) and the most frequent symptoms were neurological (82.8%) and ophthalmologic (65.6%). There were no differences in the frequencies of clinical manifestations in patients with low and high proviral load, except for urinary retention, that was more prevalent in the group with high proviral (34.8%). In summary, patients infected with HTLV-1 asymptomatic have a wide spectrum of clinical abnormalities and should be closely followed in order to identify the development of HTLV-1-associated diseases.

scholarly journals Movement Disorders Related to Gluten Sensitivity: A Systematic Review

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1034 ◽  
Author(s):  
Ana Vinagre-Aragón ◽  
Panagiotis Zis ◽  
Richard Grunewald ◽  
Marios Hadjivassiliou
Keyword(s):  
Movement Disorders ◽  
Medical Literature ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Gluten Sensitivity ◽  
Gluten Free ◽  
Inclusion Criteria ◽  
Pubmed Database ◽  
Gluten Sensitive Enteropathy ◽  
The Subject

Gluten related disorders (GRD) represent a wide spectrum of clinical manifestations that are triggered by the ingestion of gluten. Coeliac disease (CD) or gluten sensitive enteropathy is the most widely recognised, but extra-intestinal manifestations have also been increasingly identified and reported. Such manifestations may exist in the absence of enteropathy. Gluten sensitivity (GS) is another term that has been used to include all GRD, including those where there is serological positivity for GS related antibodies in the absence of an enteropathy. Gluten ataxia (GA) is the commonest extraintestinal neurological manifestation and it has been the subject of many publications. Other movement disorders (MDs) have also been reported in the context of GS. The aim of this review was to assess the current available medical literature concerning MDs and GS with and without enteropathy. A systematic search was performed while using PubMed database. A total of 48 articles met the inclusion criteria and were included in the present review. This review highlights that the phenomenology of gluten related MDs is broader than GA and demonstrates that gluten-free diet (GFD) is beneficial in a great percentage of such cases.

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