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The American Journal of Case Reports Oct 2023BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a...
A Case Report of Riboflavin Treatment and Cochlear Implants in a 4-Year-Old Girl with Progressive Hearing Loss and Delayed Speech Development: Brown-Vialetto-Van Laere Syndrome.
BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a motor neuron disorder of childhood, which can be associated with sensorineural deafness. This report describes a 4-year-old Polish girl with progressive hearing loss and delayed speech development diagnosed with Brown-Vialetto-Van Laere syndrome who was treated with riboflavin (vitamin B2) and cochlear implants. CASE REPORT The case report concerns a girl from Poland who, at the age of 2 years 10 months, developed progressive atypical neurological symptoms of unknown etiology: ataxia of the upper and lower limbs, gait abnormalities, generalized muscle weakness, visual and hearing problems, and regression of speech development. A karyotype study (whole-exome sequencing) revealed alterations within SLC52A2, leading to the diagnosis of Brown-Vialetto-Van Laere syndrome and initiation of high-dose riboflavin treatment. As a 4-year-old child, she presented to the Institute of Physiology and Pathology of Hearing - World Hearing Center in Poland with progressive hearing loss and speech regression. Hearing tests revealed bilateral profound sensorineural hearing loss with auditory neuropathy. Surgical treatment was applied in the form of bilateral cochlear implantation. CONCLUSIONS This report shows the importance of genetic testing in infants who present with atypical symptoms or signs. In this case, the diagnosis of Brown-Vialetto-Van Laere syndrome resulted in timely correction of the genetic riboflavin (vitamin B2) deficiency and improved hearing following the use of cochlear implants.
Topics: Female; Infant; Humans; Child, Preschool; Cochlear Implantation; Cochlear Implants; Speech; Hearing Loss, Sensorineural; Bulbar Palsy, Progressive; Riboflavin; Deafness
PubMed: 37786244
DOI: 10.12659/AJCR.940439 -
The Journal of Nutrition Dec 2023We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a...
We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B, or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the "ecology of anemia," which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment.
Topics: Humans; Public Health; Anemia; Iron; Iron Deficiencies; Inflammation; Anemia, Iron-Deficiency
PubMed: 37778891
DOI: 10.1016/j.tjnut.2023.05.032 -
Indian Journal of Clinical Biochemistry... Oct 2023Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an...
Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an inability to break down fatty-acids and amino acids. There are three phenotypes- type 1 and 2 are of neonatal onset and severe form, with and without congenital anomalies, respectively, and presents with acidosis, severe hypotonia, cardiomyopathy, hepatomegaly, and non-ketotic hypoglycemia. Type 3 or late-onset Multiple acyl-CoA Dehydrogenase Deficiency usually presents in the adolescent or adult age group with phenotype ranging from mild forms of myopathy and exercise intolerance to severe forms of acute metabolic decompensation on its chronic course. Type 3 Multiple acyl-CoA Dehydrogenase Deficiency rarely presents in infancy and in liver failure. We present a five-month-old developmentally normal female child with acute encephalopathy, hypotonia, non-ketotic hypoglycemia, metabolic acidosis, and liver failure, with a history of sibling death of suspected inborn error of metabolism. The blood acyl-carnitine levels in Tandem Mass Spectrometry and urinary organic acid analysis through Gas Chromatography-Mass Spectrometry were unremarkable. The patient initially responded to riboflavin, CoQ, and supportive management but ultimately succumbed to sepsis with shock and multi-organ dysfunction. The clinical exome sequencing reported a homozygous missense variation in exon 11 of the gene (chr4:g.158706270C > T) that resulted in the amino acid substitution of Leucine for Proline at codon 456 (p.Pro456Leu) suggestive of Glutaric aciduria type IIc (OMIM#231,680).
PubMed: 37746538
DOI: 10.1007/s12291-021-01007-7 -
International Journal of Rheumatic... Jan 2024A 35-year-old male patient presented fluctuating bilateral lower extremity weakness for 3 years. Physical examination showed grade 4 proximal muscle weakness in both...
A 35-year-old male patient presented fluctuating bilateral lower extremity weakness for 3 years. Physical examination showed grade 4 proximal muscle weakness in both lower extremities and grade 5 distal muscle weakness. Laboratory data revealed elevated creatine kinase, triglycerides, and cholesterol. Muscle pathology showed deposition of lipid droplet under the sarcolemma. Bone densitometry indicated severe osteoporosis. Next-generation sequencing revealed a pathogenic mutation in the ETFDH gene. The patient was diagnosed with late-onset multiple acyl-CoA dehydrogenase deficiency. After riboflavin treatment, symptoms of the patient were relieved, physical endurance was restored, and bone mineral density was improved.
Topics: Male; Humans; Adult; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Electron-Transferring Flavoproteins; Iron-Sulfur Proteins; Oxidoreductases Acting on CH-NH Group Donors; Mutation; Muscle Weakness; Osteoporosis
PubMed: 37737545
DOI: 10.1111/1756-185X.14906 -
Spectrochimica Acta. Part A, Molecular... Jan 2024The vitamins of riboflavin and folate are necessary nutrients for maintaining the proper functioning of human body. Riboflavin and folate deficiency will cause nerve...
The vitamins of riboflavin and folate are necessary nutrients for maintaining the proper functioning of human body. Riboflavin and folate deficiency will cause nerve damage, leading to peripheral neuritis, depression, tongue inflammation and other diseases. The sensitive detection of riboflavin and folate keeps its significance for patients and food quality control. In this study, a quinoline-pyridine-combined chemosensor (HQ-TPE) modified by tetraphenylethene was developed. After chelating Cd, the chemosensor exhibited high selectivity and sensitivity for riboflavin and folate. Moreover, it can discriminate the two different vitamins through different fluorescent responses, which should arise from the different intermolecular π-π interactions between the sensor HQ-TPE and the analyte upon coordination of riboflavin or folate with Cd. More importantly, the chemosensor could be used in visual semi-quantitative determination of riboflavin and folate in real samples (milk and lettuce). Therefore, the sensor presented here will not only be a powerful tool for the detection of riboflavin and folate, but also provides a new template for the design of metal complex as fluorescent sensor.
PubMed: 37678046
DOI: 10.1016/j.saa.2023.123321 -
Muscle & Nerve Nov 2023Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid...
INTRODUCTION/AIMS
Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid metabolism. In our cohort, hyperhomocysteinemia (HHcy) was common. In this study we aimed to identify the association between RR-MADD and HHcy.
METHODS
We performed a retrospective review of 13 patients with RR-MADD. Thirty-three healthy controls were recruited, and logistic regression was used to investigate the association between RR-MADD and HHcy. Muscle tissues from six patients and six controls without myopathies were collected to measure the levels of flavin adenine dinucleotide (FAD), an active form of riboflavin. Whole-exome sequencing was performed to identify the disease-associated variants.
RESULTS
The RR-MADD patients had a higher prevalence of HHcy (9 of 12) than controls (6 of 33, P < .001). In the multivariate analysis, RR-MADD was positively related to HHcy (P = .014). Muscular FAD levels were decreased in RR-MADD patients (P = .006). Thirteen variants (8 reported and 5 novel) were identified in ETFDH. Of these, c.250G > A was the most common pathogenic variant with an allelic frequency of 4 of 20.
DISCUSSION
HHcy was associated with RR-MADD and may aid in the diagnosis of the disease. Our findings expand the mutational spectrum of RR-MADD.
PubMed: 37606529
DOI: 10.1002/mus.27960 -
Annual Review of Nutrition Aug 2023Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant... (Review)
Review
Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant potential, and metabolic interactions with other micronutrients, including iron, vitamin B, and folate. Severe riboflavin deficiency, largely confined to low-income countries, clinically manifests as cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, and severe anemia with erythroid hypoplasia. Subclinical deficiency may be much more widespread, including in high-income countries, but typically goes undetected because riboflavin biomarkers are rarely measured in human studies. There are adverse health consequences of low and deficient riboflavin status throughout the life cycle, including anemia and hypertension, that could contribute substantially to the global burden of disease. This review considers the available evidence on causes, detection, and consequences of riboflavin deficiency, ranging from clinical deficiency signs to manifestations associated with less severe deficiency, and the related research, public health, and policy priorities.
Topics: Humans; Riboflavin Deficiency; Riboflavin; Causality; Antioxidants; Bone Marrow Failure Disorders; Disease Progression; Lip Diseases
PubMed: 37603429
DOI: 10.1146/annurev-nutr-061121-084407 -
Neuromolecular Medicine Dec 2023AIFM1 is a mitochondrial flavoprotein involved in caspase-independent cell death and regulation of respiratory chain complex biogenesis. Mutations in the AIFM1 gene have...
AIFM1 is a mitochondrial flavoprotein involved in caspase-independent cell death and regulation of respiratory chain complex biogenesis. Mutations in the AIFM1 gene have been associated with multiple clinical phenotypes, but the effectiveness of riboflavin treatment remains controversial. Furthermore, few studies explored the reasons underlying this controversy. We reported a 7-year-old boy with ataxia, sensorimotor neuropathy and muscle weakness. Genetic and histopathological analyses were conducted, along with assessments of mitochondrial function and apoptosis level induced by staurosporine. Riboflavin deficiency and supplementation experiments were performed using fibroblasts. A missense c.1019T > C (p. Met340Thr) variant of AIFM1 was detected in the proband, which caused reduced expression of AIFM1 protein and mitochondrial dysfunction as evidenced by downregulation of mitochondrial complex subunits, respiratory deficiency and collapse of ΔΨm. The proportion of apoptotic cells in mutant fibroblasts was lower than controls after induction of apoptosis. Riboflavin deficiency resulted in decreased AIFM1 protein levels, while supplementation with high concentrations of riboflavin partially increased AIFM1 protein levels in variant fibroblasts. In addition, mitochondrial respiratory function of mutant fibroblasts was partly improved after riboflavin supplementation. Our study elucidated the pathogenicity of the AIFM1 c.1019T > C variant and revealed mutant fibroblasts was intolerant to riboflavin deficiency. Riboflavin supplementation is helpful in maintaining the level of AIFM1 protein and mitochondrial respiratory function. Early riboflavin treatment may serve as a valuable attempt for patients with AIFM1 variant.
Topics: Male; Humans; Child; Riboflavin Deficiency; Riboflavin; Mutation, Missense; Mitochondria; Mitochondrial Diseases; Apoptosis Inducing Factor
PubMed: 37603145
DOI: 10.1007/s12017-023-08750-5 -
Frontiers in Nutrition 2023The maternal diet greatly influences the nutritional composition of human milk. With the rise of vegan diets by lactating mothers, there are concerns about the...
BACKGROUND
The maternal diet greatly influences the nutritional composition of human milk. With the rise of vegan diets by lactating mothers, there are concerns about the nutritional adequacy of their milk. Two important nutrients, vitamin B2 and carnitine, are mostly ingested via animal products.
OBJECTIVE
We investigated the influence of a vegan diet on the vitamin B2 and carnitine concentrations in milk and serum of lactating women.
METHODS
In this case-control study, 25 lactating mothers following an exclusive vegan diet were comparted to 25 healthy lactating mothers with an omnivorous diet without use of supplements. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to measure vitamin B2 and carnitine concentrations, respectively. A linear regression model was used to determine differences in human milk and serum concentrations between study groups.
RESULTS
Vitamin B2 concentrations in human milk and serum did not differ between study groups. While the human milk free carnitine (C) and acetyl carnitine (C) concentrations did not differ between study groups, serum carnitine concentrations were lower in participants following a vegan diet than in omnivorous women ( < 0.0001).
CONCLUSION
A maternal vegan diet did not affect human milk concentration of vitamin B2 and carnitine. Breastfed infants of mothers following an exclusive vegan diet therefore are likely not at increased risk of developing a vitamin B2 or carnitine deficiency.
PubMed: 37599690
DOI: 10.3389/fnut.2023.1107768 -
Journal of the Peripheral Nervous... Sep 2023Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory... (Review)
Review
Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory ataxia, muscle weakness, optic atrophy and respiratory failure. Riboflavin supplementation is beneficial in short-term reports, but the quantum of benefit in various clinical domains is not well understood. A PubMed search was conducted, which identified 94 genetically confirmed cases of RTD who received riboflavin supplementation and had follow-up assessments. Information on the clinical and functional status before and after riboflavin supplementation was collected and analysed. Seventy-six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable, though some patients had deteriorations in individual domains with no reported deaths. The domains that had the highest rates of response to riboflavin supplementation were gross motor function (93.3% improved), bulbar palsy (91.3%) and ataxia (90.0%). Improvements were also seen in limb muscle weakness, audiology, facial nerve palsy and respiratory function. Despite treatment, many patients required assistance to ambulate and had severe or profound hearing loss and some remained gastrostomy or tracheostomy dependent. Riboflavin supplementation is a lifesaving intervention for patients with RTD and results in a profound improvement in several functional domains, with early diagnosis and treatment further improving outcomes. Despite treatment, patients are left with residual disability. There is a need to accurately measure functional outcomes in children with RTD and develop additional disease-modifying therapies.
Topics: Child; Humans; Riboflavin; Bulbar Palsy, Progressive; Hearing Loss, Sensorineural; Paralysis
PubMed: 37537696
DOI: 10.1111/jns.12587