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Nutrients 2021 Apr 29;13(5). Epub 2021 Apr 29.

School of Pharmacy, University of Camerino, 62032 Camerino, Italy.

Background: Whole milk is a good source of all the nutrients, and it also contains a sufficient number of vitamins to permit regular the growth of the neonate. Dairy cow milk can create allergy in infants less than 12 months old because of the high caseins and β-lactoglobulin content. In these circumstances, donkey milk can represent a good replacement for dairy cows' milk in children affected by Cow Milk Protein Allergy (CMPA) because of its close chemical composition with human milk, mainly due to its low protein and low mineral content. Read More

Turk J Pediatr 2021 ;63(2):314-318

Department of Pediatric Metabolism, Çukurova University Faculty of Medicine, Adana, Turkey.

Background: Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare, treatable neurodegenerative disorder with a variable clinical presentation, caused by mutations in three different riboflavin transporter genes.

Case: An 11-year-old-boy presented with respiratory insufficiency and a rapidly progressive muscle weakness. He was the fifth child of a consanguineous marriage with a medical history of hearing loss. Read More

Clin Drug Investig 2021 Apr 22. Epub 2021 Apr 22.

Neurology Unit, Azienda Sanitaria Locale della Provincia di Bari, Di Venere Teaching Hospital, Via Ospedale Di Venere 1, 70131, Bari, Italy.

Riboflavin is classified as one of the water-soluble B vitamins. It is part of the functional group of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors and is required for numerous flavoprotein-catalysed reactions. Riboflavin has important antioxidant properties, essential for correct cell functioning. Read More

Cell Rep 2021 Apr;35(3):109025

School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing 100084, China; Beijing Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, Capital Medical University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address:

Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid β-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. Read More

Curr Dev Nutr 2021 Apr 13;5(4):nzab021. Epub 2021 Mar 13.

Women and Kids Theme, South Australian Health and Medical Research Institute, and Discipline of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.

Background: Nutrition surveys suggest that <10% of Canadian adults have inadequate riboflavin intakes. However, biochemical riboflavin deficiency [erythrocyte glutathione reductase activity coefficient (EGRac) ≥1.40] has been reported in 41% of young adult women living in Metro Vancouver. Read More

Neuromuscul Disord 2021 Mar 8. Epub 2021 Mar 8.

School of Biology, College of Science, University of Tehran, Tehran, Iran. Electronic address:

Sandhoff disease is a rare fatal infantile neurologic disorder. Adult onset Sandhoff is even rarer. Variability of clinical features in adult onset Sandhoff patients and overlaps between these and features of other neurologic diseases have sometimes led to mis-diagnosis. Read More

Crit Rev Biochem Mol Biol 2021 Apr 7:1-12. Epub 2021 Apr 7.

Neuromuscular Laboratory, Department of Neurosciences, University of Padova, Padova, Italy.

Electron transfer flavoprotein dehydrogenase, also called ETF-ubiquinone oxidoreductase (ETF-QO), is a protein localized in the inner membrane of mitochondria, playing a central role in the electron-transfer system. Indeed, ETF-QO mediates electron transport from flavoprotein dehydrogenases to the ubiquinone pool. ETF-QO mutations are often associated with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD, OMIM#231680), a multisystem genetic disease characterized by various clinical manifestations with different degrees of severity. Read More

Nutrients 2021 Mar 16;13(3). Epub 2021 Mar 16.

Division of Human Nutrition, Department of Global Health, Stellenbosch University, Cape Town 7505, South Africa.

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤ 40 µg/L), = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin > 40 µg/L, hemoglobin ≥ 115 g/L), = 41; (3) children without HIV (HIV-ve) and low iron stores, = 45; and (4) HIV-ve and iron sufficient non-anemic, = 45. Read More

Methods Mol Biol 2021 ;2280:263-273

Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Berlin, Germany.

Human flavin cofactor-containing enzymes constitute a small, but highly important flavoproteome. Its stability is required to ensure key metabolic functions, such as oxidative phosphorylation and beta-oxidation of fatty acid. Flavoproteome disfunction due to mutations of individual proteins or because of the lack of FMN and FAD precursor riboflavin (vitamin B2) results in clinically relevant abnormal cellular states and diseases. Read More

Methods Mol Biol 2021 ;2280:45-54

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Arcavacata di Rende, Italy.

Riboflavin is essential for cell viability. The biologically active forms of riboflavin, FMN and FAD, participate in many biochemical redox reactions including the metabolism of carbohydrates, amino acids, and lipids. Differently from bacteria, fungi, and plants which synthesize riboflavin, higher organisms have lost the ability to synthesize the vitamin and must absorb it from food and intestinal microflora production. Read More

Mol Genet Metab Rep 2021 Jun 6;27:100738. Epub 2021 Mar 6.

University Medical Center Mainz, Villa Metabolica, Department of Pediatric and Adolescent Medicine, Mainz, Germany.

Background: In infancy multiple acyl-CoA dehydrogenase deficiency (MADD) is commonly a severe inherited metabolic disease caused by genetic defects in electron transfer flavoprotein (ETF) or ETF ubiquinone oxidoreductase. Both enzymes require flavin adenine dinucleotide (FAD) as a cofactor. Riboflavin (vitamin B) is a precursor in the synthesis of FAD. Read More

Crit Rev Food Sci Nutr 2021 Mar 16:1-14. Epub 2021 Mar 16.

Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania.

Elevated plasma levels of homocysteine (Hcy) are a recognized risk factor for stroke. This relationship represents one aspect of the debated `Hcy hypothesis'. Elevated Hcy may be an independent and treatable cause of atherosclerosis and thrombotic vascular diseases. Read More

J Neuromuscul Dis 2021 Mar 6. Epub 2021 Mar 6.

Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.

Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking.

Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the "treatabolome" project. Read More

BMC Neurol 2021 Feb 27;21(1):93. Epub 2021 Feb 27.

Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a treatable lipid metabolism disorder that presents as myopathy and episodic metabolic crisis. The metabolic crisis is typically associated with prolonged fasting or physical stress; however, the mechanism of metabolic crisis is not yet fully understood.

Case Presentation: A 28-year-old Taiwanese woman presented with dyspnoea, poor appetite, and muscle weakness after using antiobesity drugs, including metformin, triiodothyronine, and topiramate. Read More

Transl Pediatr 2021 Jan;10(1):183-187

Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inborn error of metabolism in fatty acid oxidation. We described an unusual case of recurrent vomiting and abdominal pain in a child with MADD, presenting with velvet-like changes in the small intestine. Because of prominent gastrointestinal manifestations and small intestine ulcers, the patient was first diagnosed as Crohn's disease. Read More

Biol Pharm Bull 2021 ;44(2):283-286

Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital.

Riboflavin (vitamin B2) plays an important role in cellular growth and function. Riboflavin transporter 2 (RFVT2) is widely expressed in several tissues, especially in the brain and salivary glands, and plays an important role in the tissue disruption of riboflavin. During the last 10 years, mutations in SLC52A2 have been documented in patients with a rare neurological disorder known as Brown-Vialetto-Van Laere syndrome. Read More

Animal 2021 Jan 10;15(1):100003. Epub 2020 Dec 10.

Poultry Competence Centre of the Bavarian Institute for Agriculture, Mainbernheimer Strasse 101, 97318 Kitzingen, Germany.

Alternatives to riboflavin (vitamin B) production by recombinant microorganisms are needed in organic poultry production, but are cost-intensive, so that a demand-oriented riboflavin supply is necessary. Details on the riboflavin requirements of organic poultry are not available. A feed material with high native riboflavin content from fermentation of the filamentous fungus Ashbya gossypii was studied. Read More

Proc Nutr Soc 2021 Jan 28:1-6. Epub 2021 Jan 28.

Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, College of Science, Engineering and Food Science, Cork, Ireland.

In parallel with increased public awareness of the health and environmental benefits of consuming a plant-based diet, the numbers of people who identify as vegan has increased sharply. The question of whether vegetarian and vegan diets are appropriate for children is a longstanding and unresolved controversy. The more restrictive the diet and the younger the child, the greater the risk of nutritional deficiency. Read More

Plant Sci 2021 Feb 7;303:110664. Epub 2020 Sep 7.

Department of Plant Nutrition, Aula Dei Experimental Station, Consejo Superior de Investigaciones Científicas (EEAD-CSIC), Av. Montañana 1005, E-50059, Zaragoza, Spain. Electronic address:

Flavin synthesis and secretion is an integral part of the toolbox of root-borne Fe facilitators used by Strategy I species upon Fe deficiency. The Fe-deficiency responses of the wild legume Medicago scutellata grown in nutrient solution have been studied at two different pH values (5.5 and 7. Read More

JIMD Rep 2021 Jan 19;57(1):15-22. Epub 2020 Oct 19.

Department of Paediatric Metabolic Medicine Great Ormond Street Hospital NHS Trust London UK.

Background: Multiple acyl-CoA dehydrogenase (MADD) deficiency represents a rare fatty acid oxidation disorder where sporadic reports of pancreatitis already exist. Here, we report three cases of MADD with pancreatic involvement raising questions whether this represents an incidental finding or it is related to the pathophysiology of MADD.

Methods: We have retrospectively studied the clinical, biochemical and radiologic data of patients with MADD diagnosed in our department over the last 20 years to identify patients with pancreatic involvement. Read More

Dis Model Mech 2021 Jan 19. Epub 2021 Jan 19.

Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, Rome 00146, Italy

The cytoskeletal network plays a crucial role in differentiation, morphogenesis, function and homeostasis of the nervous tissue, so that alterations in any of its components may lead to neurodegenerative diseases. Riboflavin transporter deficiency (RTD), a childhood-onset disorder characterized by degeneration of motor neurons (MNs), is caused by biallelic mutations in genes encoding the human riboflavin (RF) transporters. In a patient- specific induced Pluripotent Stem Cells (iPSCs) model of RTD, we recently demonstrated altered cell-cell contacts, energy dysmetabolism and redox imbalance. Read More

Compr Rev Food Sci Food Saf 2019 Nov 11;18(6):1968-1984. Epub 2019 Sep 11.

Dept. of Nutritional Sciences, Univ. of Wisconsin-Madison, Madison, WI, 53706, U.S.A.

The prevalence of undernutrition due to insufficient energy intake has been reduced by nearly 50% since 1990. This reduction is largely attributed to improved yields of staple crops, such as wheat, rice, and maize; however, these improvements did little for micronutrient deficiencies that affect an estimated two billion people worldwide. Starchy staple crops are energy dense but are often lacking in one or more B vitamins, making resource-constrained people who consume monotonous diets comprised predominantly of these staples at risk for developing deficiency. Read More

Eur J Neurol 2021 Mar 5;28(3):945-954. Epub 2021 Jan 5.

School of Biotechnology, Madurai Kamaraj University, Madurai, India.

Background: Brown-Vialetto-Van Laere syndrome (BVVLS) and Fazio-Londe disease (FLD) are rare neurological disorders presenting with pontobulbar palsy, muscle weakness and respiratory insufficiency. Mutations in SLC52A2 (hRFVT-2) or SLC52A3 (hRFVT-3) genes can be responsible for these disorders with an autosomal recessive pattern of inheritance. The aim of this study was to screen for mutations in SLC52A2 and SLC52A3 among Indian families diagnosed with BVVLS and FLD. Read More

Antioxidants (Basel) 2020 Dec 9;9(12). Epub 2020 Dec 9.

Department of Science, LIME, University of Roma Tre, 00146 Rome, Italy.

Riboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by sensorineural deafness and motor neuron degeneration. Since riboflavin plays key functions in biological oxidation-reduction reactions, energy metabolism pathways involving flavoproteins are affected in RTD. We recently generated induced pluripotent stem cell (iPSC) lines from affected individuals as an in vitro model of the disease and documented mitochondrial impairment in these cells, dramatically impacting cell redox status. Read More

Int J Biochem Cell Biol 2021 Mar 3;132:105899. Epub 2020 Dec 3.

Human Metabolomics, North-West University, Potchefstroom, South Africa. Electronic address:

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD), or glutaric aciduria type II (GAII), is a group of clinically heterogeneous disorders caused by mutations in electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) - the two enzymes responsible for the re-oxidation of enzyme-bound flavin adenine dinucleotide (FADH) via electron transfer to the respiratory chain at the level of coenzyme Q10. Over the past decade, an increasing body of evidence has further coupled mutations in FAD metabolism (including intercellular riboflavin transport, FAD biosynthesis and FAD transport) to MADD-like phenotypes. In this review we provide a detailed description of the overarching and specific metabolic pathways involved in MADD. Read More

BMC Neurol 2020 Dec 2;20(1):436. Epub 2020 Dec 2.

Neurology Department, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.

Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare and treatable inherited lipid storage myopathy. Here, we report an elderly patient with MADD mimicking myositis.

Case Presentation: An 80-year-old woman had progressive weakness in her limbs, exercise intolerance, and no muscle pain for 3 months. Read More

Food Funct 2020 Dec 19;11(12):10979. Epub 2020 Nov 19.

Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China.

Correction for 'Dietary riboflavin deficiency induces genomic instability of esophageal squamous cells that is associated with gut microbiota dysbiosis in rats' by Feng Pan et al., Food Funct., 2020, DOI: . Read More

JIMD Rep 2020 Nov 21;56(1):9-13. Epub 2020 Sep 21.

Metabolic-Neurogenetic Clinic Edith Wolfson Medical Center Holon Israel.

Acyl-CoA dehydrogenase family member 9 (ACAD9) is an enzyme essential for the assembly of mitochondrial respiratory chain complex I. ACAD9 deficiency can cause lactic acidosis, myopathy, cardiomyopathy, intellectual disability, and early demise. We present a patient with mitochondrial myopathy, hypertrophic cardiomyopathy, and epilepsy due to recessive ACAD9 mutations. Read More

An Pediatr (Barc) 2020 Nov 3. Epub 2020 Nov 3.

Servicio de Farmacia, Hospital San Pedro, Logroño, España.

Introduction: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. Read More