Search Our Scientific Publications & Authors

Mol Genet Metab 2021 Jul 11;133(3):257-260. Epub 2021 May 11.

Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address:

Background: High rates of lost to follow-up (LTFU) adult patients are a major concern in the long-term management of phenylketonuria (PKU). To address this issue, we designed the project "Backtoclinic" with the purpose of identifying LTFU adult PKU patients in Austria as a first step to reestablish appropriate treatment.

Subjects And Methods: Individuals born between 1966 and 1999 and diagnosed with PKU through the National Austrian Newborn Screening Program (NANSP) were identified using the NANSP's database. Read More

EMBO Mol Med 2021 May 27:e13943. Epub 2021 May 27.

Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism (AGEM), Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Depletion of nicotinamide adenine dinucleotide (NAD ), a central redox cofactor and the substrate of key metabolic enzymes, is the causative factor of a number of inherited and acquired diseases in humans. Primary deficiencies of NAD homeostasis are the result of impaired biosynthesis, while secondary deficiencies can arise due to other factors affecting NAD homeostasis, such as increased NAD consumption or dietary deficiency of its vitamin B3 precursors. NAD depletion can manifest in a wide variety of pathological phenotypes, ranging from rare inherited defects, characterized by congenital malformations, retinal degeneration, and/or encephalopathy, to more common multifactorial, often age-related, diseases. Read More

Br J Clin Pharmacol 2021 May 22. Epub 2021 May 22.

Dicerna Pharmaceuticals, Cambridge, MA, USA.

RNA interference (RNAi) is a natural biological pathway that inhibits gene expression by targeted degradation or translational inhibition of cytoplasmic mRNA by the RNA induced silencing complex. RNAi has long been exploited in laboratory research to study the biological consequences of the reduced expression of a gene of interest. More recently RNAi has been demonstrated as a therapeutic avenue for rare metabolic diseases. Read More

Mov Disord 2021 May 7. Epub 2021 May 7.

IRCCS Mondino Foundation, Pavia, Italy.

X-linked parkinsonism encompasses rare heterogeneous disorders mainly inherited as a recessive trait, therefore being more prevalent in males. Recent developments have revealed a complex underlying panorama, including a spectrum of disorders in which parkinsonism is variably associated with additional neurological and non-neurological signs. In particular, a childhood-onset encephalopathy with epilepsy and/or cognitive disability is the most common feature. Read More

Int J Biochem Cell Biol 2021 May 18;134:105951. Epub 2021 Feb 18.

Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. Electronic address:

Mitochondria are highly dynamic organelles, which undergo frequent structural and metabolic changes to fulfil cellular demands. To facilitate these processes several proteins are required to regulate mitochondrial shape and interorganellar communication. These proteins include the classical mitochondrial fusion (MFN1, MFN2, and OPA1) and fission proteins (DRP1, MFF, FIS1, etc. Read More

J Lipid Atheroscler 2021 Jan 1;10(1):1-7. Epub 2020 Dec 1.

Department of Pediatrics and Medical Genetics & Genomics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Mitochondrial fatty acid β-oxidation (mFAO), which is the major pathway for the degradation of fatty acids and is critical for maintaining energy homeostasis in the human body, consists of carnitine transport, the carnitine shuttle, and fatty acid β-oxidation. Inherited metabolic defects of mFAO result in more than 15 distinct mFAO disorders (mFAODs) with varying clinical manifestations. The common elements of the clinical presentation of mFAODs are hypoketotic hypoglycemia, (cardio)myopathy, arrhythmia, and rhabdomyolysis, indicating the importance of FAO during fasting or stressful situations. Read More

Rev Med Interne 2021 Jan 14. Epub 2021 Jan 14.

Centre de compétence des maladies neuromusculaires, Centre Hospitalier et Universitaire, avenue côte de nacre, 14033 Caen cedex, France.

Mitochondrial diseases, characterized by a respiratory chain deficiency, are considered as rare genetic diseases but are the most frequent among inherited metabolic disorders. The complexity of their diagnosis is due to the dual control by the mitochondrial (mtDNA) and the nuclear DNA (nDNA), and to the heterogeneous clinical presentations; illegitimate association of symptoms should prompt the clinician to evoke a mitochondrial disorder. The goals of this review are to provide clinicians a better understanding of mitochondrial diseases in adults. Read More

Int J Mol Sci 2021 Jan 12;22(2). Epub 2021 Jan 12.

Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease with low clinical penetrance, caused by mutations in the hydroxymethylbilane synthase () gene, which encodes the third enzyme in the haem biosynthesis pathway. In susceptible mutation carriers, triggering factors such as hormonal changes and commonly used drugs induce an overproduction and accumulation of toxic haem precursors in the liver. Clinically, this presents as acute attacks characterised by severe abdominal pain and a wide array of neurological and psychiatric symptoms, and, in the long-term setting, the development of primary liver cancer, hypertension and kidney failure. Read More

G Ital Nefrol 2020 Dec 7;37(6). Epub 2020 Dec 7.

Sezione di Nefrologia, Dipartimento di Scienze Mediche Traslazionali, Università degli Studi della Campania "L. Vanvitelli", Napoli, Italy.

The recent application of proteomics and metabolomics to clinical medicine has demonstrated their potential role in complementing genomics for a better understanding of diseases' patho-physiology. These technologies offer the clear opportunity to identify risk factors, disease-specific or stage-specific biomarkers and to predict therapeutic response. This article is an overview of the recent insights obtained by metabolomic and proteomic studies in inherited kidney disorders. Read More

Curr Opin Clin Nutr Metab Care 2021 Jan;24(1):62-70

Section of Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Purpose Of Review: Metabolism of sulfur amino acids (SAA) provides compounds important for many cellular functions. Inherited disorders of SAA metabolism are typically severe multisystemic diseases affecting brain, liver, connective tissue, or vasculature. The review summarizes the present therapeutic approaches and advances in identifying novel treatment targets, and provides an overview of new therapies. Read More

Pediatr Blood Cancer 2020 12 24;67(12):e28722. Epub 2020 Sep 24.

Department of Pediatrics, Division of Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background: Brain atrophy, abnormal pituitary morphology, corpus callosum, and posterior fossa abnormalities have been described in patients with Fanconi anemia (FA). We aimed to provide an overview of cranial neuroimaging findings and to evaluate the clinical implications in FA patients.

Procedure: Cranial magnetic resonance imaging (MRI) studies of 34 patients with FA were retrospectively evaluated, and patients' clinical data were correlated with the imaging findings. Read More

Front Mol Biosci 2020 14;7:153. Epub 2020 Jul 14.

Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, South Korea.

Branched chain fatty acids perform very important functions in human diet and drug metabolism. they cannot be metabolized in mitochondria and are instead processed and degraded in peroxisomes due to the presence of methyl groups on the carbon chains. Oxidative degradation pathways for lipids include α- and β-oxidation and several pathways. Read More

Prev Med Rep 2020 Sep 8;19:101142. Epub 2020 Jun 8.

School of Sport and Exercise Sciences, Swansea University, Bay Campus, Swansea, Wales, UK.

Regular physical activity is associated with physiological and psychosocial benefits in both healthy and clinical populations. However, little is known about tailoring the analysis of physical activity using accelerometers to the specific characteristics of chronic conditions. Whilst accelerometry is broadly used to assess physical activity, recommendations on calibration in paediatric clinical groups are warranted. Read More

Drugs 2020 Jul;80(11):1053-1063

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Hemoglobinopathies are among the most common monogenic diseases worldwide. Approximately 1-5% of the global population are carriers for a genetic thalassemia mutation. The thalassemias are characterized by autosomal recessive inherited defects in the production of hemoglobin. Read More

Eur J Ophthalmol 2020 Nov 19;30(6):1220-1227. Epub 2020 Jun 19.

Medicines Authority, San Ġwann, Malta.

Leber's hereditary optic neuropathy (LHON) is a rare, maternally-inherited optic neuropathy caused by mitochondrial DNA point mutations and which can cause blindness. Currently, Raxone (idebenone) is the only available medicinal product authorised to treat LHON within the European Union and LHON remains an unmet medical need. The aim of this article was to summarise interventional clinical trials published over the past 5 years (between 2014 and 2019) with the primary purpose of treating LHON. Read More

Orphanet J Rare Dis 2020 06 11;15(1):146. Epub 2020 Jun 11.

Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology, 4700 KAUST, Thuwal, 23955, Kingdom of Saudi Arabia.

Background: Inborn errors of metabolism (IEM) represent a subclass of rare inherited diseases caused by a wide range of defects in metabolic enzymes or their regulation. Of over a thousand characterized IEMs, only about half are understood at the molecular level, and overall the development of treatment and management strategies has proved challenging. An overview of the changing landscape of therapeutic approaches is helpful in assessing strategic patterns in the approach to therapy, but the information is scattered throughout the literature and public data resources. Read More

Biochim Biophys Acta Gen Subj 2020 10 5;1864(10):129652. Epub 2020 Jun 5.

Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB, F-91191 Gif sur Yvette, France. Electronic address:

Background: Glycosylation is one of the most complex post-translational modifications of proteins and lipids, notably requiring many glycosyltransferases, glycosidases and sugar transporters encoded by about 1-2% of all human genes. Deleterious variants in any of them may result in improper protein or lipid glycosylation, thus yielding the so-called 'congenital disorders of glycosylation' or CDG.

Scope Of Review: We first review the current state of knowledge on the common blood and cellular glycoproteins used in the biochemical screening of CDG, as well as the emerging ones for an improved diagnosis. Read More

J Inherit Metab Dis 2021 Jan 3;44(1):72-87. Epub 2020 Jun 3.

Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Antisense oligonucleotide (AON) therapies involve short strands of modified nucleotides that target RNA in a sequence-specific manner, inducing targeted protein knockdown or restoration. Currently, 10 AON therapies have been approved in the United States and Europe. Nucleotides are chemically modified to protect AONs from degradation, enhance bioavailability and increase RNA affinity. Read More

Biochim Biophys Acta Biomembr 2020 12 8;1862(12):183336. Epub 2020 May 8.

Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Disorders caused by defects in lysosomal membrane transporters form a distinct subgroup of lysosomal storage disorders (LSDs). To date, defects in only 10 lysosomal membrane transporters have been associated with inherited disorders. The clinical presentations of these diseases resemble the phenotypes of other LSDs; they are heterogeneous and often present in children with neurodegenerative manifestations. Read More

Molecules 2020 Apr 13;25(8). Epub 2020 Apr 13.

Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube Str. 40, 06120 Halle (Saale), Germany.

Carnitine palmitoyltransferase (CPT) catalyzes the transfer of long- and medium-chain fatty acids from cytoplasm into mitochondria, where oxidation of fatty acids takes place. Deficiency of CPT enzyme is associated with rare diseases of fatty acid metabolism. CPT is present in two subforms: CPT I at the outer mitochondrial membrane and carnitine palmitoyltransferase II (CPT II) inside the mitochondria. Read More

Adv Ther 2020 05 8;37(5):1866-1896. Epub 2020 Apr 8.

Child Nutrition and Metabolic Diseases Unit, University Hospital La Paz, Madrid, Spain.

Introduction: Liver transplantation is recognised as a treatment option for patients with propionic acidemia (PA) and those with methylmalonic acidemia (MMA) without renal impairment. In patients with MMA and moderate-to-severe renal impairment, combined liver-kidney transplantation is indicated. However, clinical experience of these transplantation options in patients with PA and MMA remains limited and fragmented. Read More

J Bras Nefrol 2020 Mar;42(2):219-230

Universidade Federal do Paraná, Departamento de Clínica Médica, Serviço de Nefrologia, Curitiba, PR, Brasil.

There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Read More

Front Neurol 2019 18;10:1369. Epub 2020 Feb 18.

Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands.

Progressive intellectual and neurological deterioration (PIND) is a rare but severe childhood disorder characterized by loss of intellectual or developmental abilities, and requires quick diagnosis to ensure timely treatment to prevent possible irreversible neurological damage. Inborn errors of metabolism (IEMs) constitute a group of more than 1,000 monogenic conditions in which the impairment of a biochemical pathway is intrinsic to the pathophysiology of the disease, resulting in either accumulation of toxic metabolites and/or shortage of energy and building blocks for the cells. Many IEMs are amenable to treatment with the potential to improve outcomes. Read More

Mol Genet Genomic Med 2020 03 23;8(3):e1143. Epub 2020 Jan 23.

Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive inherited disorder which is characterized by neurological and vegetative symptoms. To date, only 130 patients with AADCD have been reported worldwide.

Methods: We demonstrated 14 previously undescribed patients together with three reportedly patients in Mainland China. Read More

J Cardiovasc Electrophysiol 2020 02 15;31(2):570-578. Epub 2020 Jan 15.

Cardiology Division, Cardiovascular Genetics Program, Massachusetts General Hospital, Boston, Massachusetts.

Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) can be attributed to cardiac, respiratory, metabolic, and toxicologic etiologies. Most cases of SCD are caused by coronary artery disease and approximately 40% of cardiac arrests are unexplained. Inherited arrythmias and cardiomyopathies are important contributors to SCA and SCD. Read More

Dig Liver Dis 2020 04 2;52(4):359-367. Epub 2020 Jan 2.

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

Lysosomal storage diseases (LSDs) are a heterogeneous group of inherited disorders caused by loss-of-function mutations in genes encoding for lysosomal enzymes/proteins. The consequence is a progressive accumulation of substrates in these intracellular organelles, resulting in cellular and tissue damage. The overall incidence is about 1/8000 live births, but is likely underestimated. Read More

J Clin Med 2019 Dec 12;8(12). Epub 2019 Dec 12.

IMAiA-Institute for Molecular Biology and RNA Technology, Faculty of Health, Universiteitssingel 50, 6229ER Maastricht, The Netherlands.

The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand of cardiomyocytes, involving an intricate network of pathways regulating the metabolic flux of substrates. The failure of these processes results in structural and functional deficiencies of the cardiac muscle, including inherited cardiomyopathies. Read More

Mol Genet Metab 2020 01 21;129(1):3-12. Epub 2019 Nov 21.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical School, Durham, NC, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.. Electronic address:

The glycogen storage diseases are a group of inherited metabolic disorders that are characterized by specific enzymatic defects involving the synthesis or degradation of glycogen. Each disorder presents with a set of symptoms that are due to the underlying enzyme deficiency and the particular tissues that are affected. Autophagy is a process by which cells degrade and recycle unneeded or damaged intracellular components such as lipids, glycogen, and damaged mitochondria. Read More

J Clin Pathol 2020 Jul 22;73(7):384-390. Epub 2019 Nov 22.

Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Monogenic dyslipidaemia is a diverse group of multisystem disorders. Patients may present to various specialities from early childhood to late in adult life, and it usually takes longer before the diagnosis is established. Increased awareness of these disorders among clinicians is imperative for early diagnosis. Read More

Mol Genet Metab 2020 02 31;129(2):47-58. Epub 2019 Oct 31.

Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy; Department of NEUROFARBA, University of Florence, Florence, Italy. Electronic address:

Lysosomal storage diseases (LSDs) are rare to extremely rare monogenic disorders. Their incidence, however, has probably been underestimated owing to their complex clinical manifestations. Sialidosis is a prototypical LSD inherited as an autosomal recessive trait and caused by mutations in the NEU1 gene that result in a deficiency of alpha-N-acetyl neuraminidase 1 (NEU1). Read More