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J Neurol Neurosurg Psychiatry 2018 Nov 22. Epub 2018 Nov 22.

Department of Neuroinflammation, UCL Institute of Neurology, London, UK.

Adult-onset leukodystrophies and genetic leukoencephalopathies comprise a diverse group of neurodegenerative disorders of white matter with a wide age of onset and phenotypic spectrum. Patients with white matter abnormalities detected on MRI often present a diagnostic challenge to both general and specialist neurologists. Patients typically present with a progressive syndrome including various combinations of cognitive impairment, movement disorders, ataxia and upper motor neuron signs. Read More

Genet Med 2018 Sep 12. Epub 2018 Sep 12.

INSERM, U 1127, CNRS UMR 7225, Sorbonne Universites, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle epiniere, ICM, Paris, France.

Purpose: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences.

Methods: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. Read More

Cogn Neuropsychol 2018 May - Jun;35(3-4):113-119

a School of Life and Health Sciences, Aston University , Birmingham , UK.

This is an introduction to the special issue on cognitive impairments in inherited metabolic diseases (IMD). It provides an overview of the studies included, focusing on the possibility of selective impairments which could provide unique evidence on the specificity of neural circuitries mediating cognitive functions. It will suggest that these circuitries have different metabolic properties which make them especially apt to carry out certain functions, but also particularly susceptible to certain forms of metabolic disruption. Read More

J Pediatr Health Care 2018 May - Jun;32(3):285-294

Lysosomal storage disorders (LSDs) are a heterogeneous group of approximately 50 rare inherited metabolic conditions that result from enzyme deficiencies that interfere with lysosome function. Although often grouped together, there is great variability regarding age of onset, severity, treatment, and outcomes for each disorder and subtype. Currently, laboratory methods are available to test newborns for seven of these conditions. Read More

Pan Afr Med J 2017 30;28:185. Epub 2017 Oct 30.

Unité de Neuropédiatrie, Service de Pédiatrie II, Hôpital d'Enfants de Rabat, Maroc.

Introduction: X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disease, due to mutations in the ABCD1 gene. It manifests as a damage to the central and peripheral nervous system, adrenal insufficiency and testicular damage in children. Diagnosis is based on the determination of long-chain saturated fatty acids. Read More

Kidney Blood Press Res 2018 16;43(2):406-421. Epub 2018 Mar 16.

Nephrology and Renal Transplant Department, Hospital Clinic, University of Barcelona, RedInRen, Barcelona, Spain.

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. Read More

Glycobiology 2018 06;28(6):382-391

Research Unit For Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, 12808, Czech Republic.

Blood group B glycosphingolipids (B-GSLs) are substrates of the lysosomal alpha-galactosidase A (AGAL). Similar to its major substrate-globotriaosylceramide (Gb3Cer)-B-GSLs are not degraded and accumulate in the cells of patients affected by an inherited defect of AGAL activity (Fabry disease-FD).The pancreas is a secretory organ known to have high biosynthesis of blood group GSLs. Read More

Pediatr Clin North Am 2018 04;65(2):179-208

Neurology Department, Neurometabolic Unit, Hospital Sant Joan de Deu and CIBERER-ISCIII, Passeig Sant Joan de Deu 28950 Esplugues de Llobregat, Barcelona, Spain.

The specialty of inherited metabolic disease is at the forefront of progress in medicine, with new methods in metabolomics and genomics identifying the molecular basis for a growing number of conditions and syndromes. This review presents an updated pathophysiologic classification of inborn errors of metabolism and a method of clinical screening in neonates, late-onset emergencies, neurologic deterioration, and other common clinical scenarios. When and how to investigate a metabolic disorder is presented to encourage physicians to use sophisticated biochemical investigations and not miss a treatable disorder. Read More

J Genet Genomics 2018 Feb 14;45(2):61-70. Epub 2018 Feb 14.

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address:

Inborn errors of metabolism (IEMs) are a large group of inherited disorders characterized by disruption of metabolic pathways due to deficient enzymes, cofactors, or transporters. The rapid advances in the understanding of the molecular pathophysiology of many IEMs, have led to significant progress in the development of many new treatments. The institution and continued expansion of newborn screening provide the opportunity for early treatment, leading to reduced morbidity and mortality. Read More

Genes (Basel) 2018 Feb 6;9(2). Epub 2018 Feb 6.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy, I.C.G.E.B., Padriciano 99, 34149 Trieste, Italy.

Lysosomal storage disorders (LSDs) represent a group of more than 50 severe metabolic diseases caused by the deficiency of specific lysosomal hydrolases, activators, carriers, or lysosomal integral membrane proteins, leading to the abnormal accumulation of substrates within the lysosomes. Numerous mutations have been described in each disease-causing gene; among them, about 5-19% affect the pre-mRNA splicing process. In the last decade, several strategies to rescue/increase normal splicing of mutated transcripts have been developed and LSDs represent excellent candidates for this type of approach: (i) most of them are inherited in an autosomic recessive manner and patients affected by late-onset (LO) phenotypes often retain a fair amount of residual enzymatic activity; thus, even a small recovery of normal splicing may be beneficial in clinical settings; (ii) most LSDs still lack effective treatments or are currently treated with extremely expensive approaches; (iii) in few LSDs, a single splicing mutation accounts for up to 40-70% of pathogenic alleles. Read More

Postgrad Med J 2018 May 31;94(1111):296-304. Epub 2018 Jan 31.

Molecular Physiology Laboratory, Centre for Atherothrombotic and Metabolic Disease, Hull York Medical School, University of Hull, Hull, UK.

Duchenne muscular dystrophy (DMD) is a progressive wasting disease of skeletal and cardiac muscles, representing one of the most common recessive fatal inherited genetic diseases with 1:3500-1:5000 in yearly incidence. It is caused by mutations in the DMD gene that encodes the membrane-associated dystrophin protein. Over the years, many have been the approaches to management of DMD, but despite all efforts, no effective treatment has yet been discovered. Read More

Sci Rep 2017 Dec 15;7(1):17641. Epub 2017 Dec 15.

Department of Human Genetics, CHU Sart-Tilman, University of Liège, Liège, Belgium.

The range of applications performed on dried blood spots (DBS) widely broadened during the past decades to now include next-generation sequencing (NGS). Previous publications provided a general overview of NGS capacities on DBS-extracted DNA but did not focus on the identification of specific disorders. We thus aimed to demonstrate that NGS was reliable for detecting pathogenic mutations on genomic material extracted from DBS. Read More

Indian J Ophthalmol 2017 Nov;65(11):1087-1092

Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, Tami Nadu, India.

Leber's hereditary optic neuropathy (LHON) is a common inherited mitochondrial disorder that is characterized by the degeneration of the optic nerves, leading to vision loss. The major mutations in the mitochondrial genes ND1, ND4, and ND6 of LHON subjects are found to increase the oxidative stress experienced by the optic nerve cell, thereby leading to nerve cell damage. Accurate treatments are not available and drugs that are commercially available like Idebenone, EPI-743, and Bendavia with their antioxidant role help in reducing the oxidative stress experienced by the cell thereby preventing the progression of the disease. Read More

Mol Genet Metab 2017 12 7;122(4):145-152. Epub 2017 Oct 7.

Children's National Health System, Division of Genetics and Metabolism, United States; Rare Diseases Institute, Division of Genetics and Metabolism, United States. Electronic address:

Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB to form a hetero-dodecamer. Dysfunction of PCC leads to the inherited metabolic disorder propionic acidemia, which can result in an affected individual presenting with metabolic acidosis, hyperammonemia, lethargy, vomiting and sometimes coma and death if not treated. Individuals with propionic acidemia also have a number of long term complications resulting from the dysfunction of the PCC enzyme. Read More

Arch Dis Child Educ Pract Ed 2018 Aug 26;103(4):213-216. Epub 2017 Aug 26.

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, West Midlands, UK.

H-Magnetic Resonance Spectroscopy (MRS) is a novel advanced imaging technique used as an adjunct to MRI to reveal complementary non-invasive information about the biochemical composition of imaged tissue. Clinical uses in paediatrics include aiding diagnosis of brain tumours, neonatal disorders such as hypoxic-ischaemic encephalopathy, inherited metabolic diseases, traumatic brain injury, demyelinating conditions and infectious brain lesions. MRS has potential to improve diagnosis and treatment monitoring of childhood brain tumours and other CNS diseases, facilitate biopsy and surgical planning, and provide prognostic biomarkers. Read More

Methods Mol Biol 2017 ;1646:113-135

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

Venous thromboembolism, usually entailing deep vein thrombosis, pulmonary embolism, or both, is a complex and multifactorial disorder, in which a number of putative conditions interplay and finally contribute to propel the individual risk over a certain degree, so ultimately culminating in the development of venous occlusive disorders. Thrombophilia is commonly defined as a propensity to develop venous thromboembolism on the basis of an underlying hypercoagulable state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis. The thrombophilic conditions are conventionally classified as inherited (or genetically determined) and acquired. Read More

Transl Res 2017 11 15;189:65-75. Epub 2017 Jun 15.

Department of Chemistry, Cleveland State University, Cleveland, Ohio. Electronic address:

Metabolomics can be described as a simultaneous and comprehensive analysis of small molecules in a biological sample. Recent technological and bioinformatics advances have facilitated large-scale metabolomic studies in many areas, including inborn errors of metabolism (IEMs). Despite significant improvements in the diagnosis and treatment of some IEMs, it is still challenging to understand how genetic variation affects disease progression and susceptibility. Read More

J Inherit Metab Dis 2017 07 30;40(4):543-554. Epub 2017 May 30.

Unit of Pediatric Immunohematology and Stem Cell Program, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Lysosomal storage diseases (LSDs) are rare inherited metabolic disorders characterized by a dysfunction in lysosomes, leading to waste material accumulation and severe organ damage. Enzyme replacement therapy (ERT) and haematopoietic stem cell transplant (HSCT) have been exploited as potential treatments for LSDs but pre-clinical and clinical studies have shown in some cases limited efficacy. Intravenous ERT is able to control the damage of visceral organs but cannot prevent nervous impairment. Read More

Cell Tissue Res 2017 07 22;369(1):63-73. Epub 2017 Apr 22.

Department of Dermatology, University Medical Center Freiburg, Hauptstrasse 7, 79104, Freiburg, Germany.

Renal-skin syndroms are a group of genetic disorders with renal and cutaneous manifestations that target molecular components present in both organs. Inherited renal-skin syndromes are mainly associated with defects of cell-matrix adhesion. We provide a non-exhaustive overview of the main molecular players at cell-matrix adhesions in mouse models and in human genetic disorders affecting kidney and skin. Read More

Neurobiol Dis 2017 Sep 24;105:300-320. Epub 2017 Feb 24.

KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium; VIB - Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium. Electronic address:

Peripheral neuropathies are characterized by a progressive and length-dependent loss of peripheral nerve function. This can be caused either by genetic defects, classified as 'inherited peripheral neuropathies', or they can be acquired throughout life. In that case, the disease is caused by various insults such as toxins and mechanical injuries, or it can arise secondary to medical conditions such as metabolic disorders, nutritional deficiencies, inflammation and infections. Read More

J Biol Regul Homeost Agents 2016 Jul-Sep;30(3):909-914

Department of Health Sciences, Forensic Sciences Section, University of Florence, Florence, Italy.

Starting from an international overview of the current status of screening programs, the present paper focuses on the legal situation in Italy and the great differences among Italian regions. Since the introduction of tandem mass spectrometry (MS/MS) in the ‘90s the paradigm “one spot-one disease” changed. Only recently, some regions issued legislative acts to promote expanded newborn screening with MS/MS. Read More

J Obstet Gynaecol Can 2016 08;38(8):742-762.e3

Vancouver BC.

Objective: This guideline was written to update Canadian maternity care and reproductive healthcare providers on pre- and postconceptional reproductive carrier screening for women or couples who may be at risk of being carriers for autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL) conditions, with risk of transmission to the fetus. Four previous SOGC- Canadian College of Medical Geneticists (CCMG) guidelines are updated and merged into the current document.

Intended Users: All maternity care (most responsible health provider [MRHP]) and paediatric providers; maternity nursing; nurse practitioner; provincial maternity care administrator; medical student; and postgraduate resident year 1-7. Read More

Semin Cell Dev Biol 2017 04 12;64:213-223. Epub 2016 Aug 12.

Pathophysiology of Striated Muscles Laboratory, Unit of Functional and Adaptive Biology (BFA), University Paris Diderot, Sorbonne Paris Cité, BFA, UMR CNRS 8251, 75250, Paris Cedex 13, France; AP-HP, Centre de Référence Maladies Neuromusculaires Paris-Est, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France. Electronic address:

Because of their contractile activity and their high oxygen consumption and metabolic rate, skeletal muscles continually produce moderate levels of reactive oxygen and nitrogen species (ROS/RNS), which increase during exercise and are buffered by multiple antioxidant systems to maintain redox homeostasis. Imbalance between ROS/RNS production and elimination results in oxidative stress (OxS), which has been implicated in ageing and in numerous human diseases, including cancer, diabetes or age-related muscle loss (sarcopenia). The study of redox homeostasis in muscle was hindered by its lability, by the many factors influencing technical OxS measures and by ROS/RNS important roles in signaling pathways and adaptative responses to muscle contraction and effort, which make it difficult to define a threshold between physiological signaling and pathological conditions. Read More

Semin Ophthalmol 2017 15;32(6):707-714. Epub 2016 Jul 15.

a Department of Sense Organs, Section of Ophthalmology , University of Rome "Sapienza," Rome , Italy.

Mucopolysaccharidoses (MPS) are a heterogeneous group of rare inherited disorders, characterized by the lack or malfunction of lysosomal enzymes necessary for glycosaminoglycan (GAGs) catabolism, and their subsequent accumulation in many tissues and organs throughout the body. An overview of the current knowledge of corneal and anterior segment manifestations in patients with MPS was provided and clinical guidelines for their diagnosis and management were furnished. The anterior segment of the eye is usually involved in every subtype of MPS, with major complications including varying degrees of corneal opacification and raised intraocular pressure (IOP) with development of glaucoma. Read More

Biomed Res Int 2016 14;2016:9210408. Epub 2016 Jun 14.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", 80121 Naples, Italy.

Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Read More

Gene 2016 Sep 16;590(1):128-41. Epub 2016 Jun 16.

Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Electronic address:

The evolutionarily conserved human polymerase delta (POLD1) gene encodes the large p125 subunit which provides the essential catalytic activities of polymerase δ (Polδ), mediated by 5'-3' DNA polymerase and 3'-5' exonuclease moieties. POLD1 associates with three smaller subunits (POLD2, POLD3, POLD4), which together with Replication Factor C and Proliferating Nuclear Cell Antigen constitute the polymerase holoenzyme. Polδ function is essential for replication, with a primary role as the replicase for the lagging strand. Read More

Pharmacol Ther 2016 09 8;165:132-52. Epub 2016 Jun 8.

Centre for Eye Research Australia, 75 Commercial Road, Melbourne, 3004, Victoria, Australia; Ophthalmology, University of Melbourne, Department of Surgery, Australia. Electronic address:

Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Read More

Clin Rev Allergy Immunol 2018 Jun;54(3):446-453

Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.

Innate immunity is a critical partner in the regulation of inflammation and some mutations in genes implied in innate immunity pathways can cause genetic disorders characterized by seemingly unprovoked self-limited inflammatory attacks. These rare conditions are collectively named "hereditary periodic fever syndromes" (HPFS), and protean pathogenetic mechanisms combined with several clinical phenotypes characterize at least four distinct conditions: (1) familial Mediterranean fever, which is the prototype and the most widely recognized among HPFS, inherited as an autosomal recessive disorder showing recurrent dysregulated inflammatory processes, caused by an abnormal interaction between cytoskeleton and inflammasome, a key-signaling platform that releases interleukin-1β (IL-1β); (2) the group of cryopyrin-associated periodic syndrome, which upsets directly the production of IL-1β, with a dominant pattern of inheritance; (3) tumor necrosis factor receptor-associated periodic syndrome, which is an autosomal dominant disorder subverting the functions and traffic of a cell membrane protein; and (4) mevalonate kinase deficiency, which is an autosomal recessive metabolic disorder halting the biosynthesis of cholesterol. MEFV, NLRP3, TNFRSF1A, and MVK are respectively the four causing genes of these conditions, all resulting in excessive IL-1β signaling, though the encoded proteins act at different levels in cytoskeletal filament organization, apoptosis, and activation of the IL-1β-structured inflammasome. Read More

Curr Protoc Hum Genet 2016 Apr 1;89:17.1.1-17.1.16. Epub 2016 Apr 1.

University of Alabama at Birmingham, Birmingham, Alabama.

Biochemical genetics focuses on the pathophysiology, diagnosis, and treatment of inherited metabolic disorders. While individually rare, the combined incidence of these diseases makes them a significant source of morbidity and mortality, particularly among infants and young children, and new conditions continue to be identified. Inherited metabolic disorders may present as an acute, life-threatening illness or with more chronic, progressive symptoms. Read More

Int J Paediatr Dent 2016 Nov 31;26(6):426-438. Epub 2016 Mar 31.

Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.

Background: Hypophosphatasia (HPP) is a rare inherited metabolic disease in which mutations in the ALPL gene (encoding tissue-nonspecific alkaline phosphatase) result in varying degrees of enzyme deficiency. HPP manifests in a spectrum of symptoms, including early primary tooth loss (root intact) and alveolar bone mineralisation defects.

Objective: To provide an overview of HPP for dental professionals to help recognise and differentially diagnose patients for appropriate referral to a specialist team. Read More

Curr Opin Cardiol 2016 May;31(3):266-74

aStanford Cardiovascular Institute bDepartment of Medicine, Division of Cardiology cDepartment of Radiology dInstitute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.

Purpose Of Review: The article provides an overview of advances in the induced pluripotent stem cell field to model cardiomyopathies of inherited inborn errors of metabolism and acquired metabolic syndromes in vitro.

Recent Findings: Several inborn errors of metabolism have been studied using 'disease in a dish' models, including Pompe disease, Danon disease, Fabry disease, and Barth syndrome. Disease phenotypes of complex metabolic syndromes, such as diabetes mellitus and aldehyde dehydrogenase 2 deficiency, have also been observed. Read More

Int J Hematol 2016 Apr 12;103(4):373-9. Epub 2016 Feb 12.

Service d'Hématologie Greffe, Hôpital Saint-Louis, AP-HP et Université Paris 7-Paris Diderot, Paris, France.

Inherited bone marrow failure (IBMF) syndromes are a heterogeneous group of rare hematological disorders characterized by the impairment of hematopoiesis, which harbor specific clinical presentations and pathogenic mechanisms. Some of these syndromes may progress through clonal evolution, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Most prominent are failures of DNA repair such as Fanconi Anemia and much rarer failure of ribosomal apparatus, e. Read More

Acta Pharmacol Sin 2016 Feb 30;37(2):143-9. Epub 2015 Nov 30.

Laboratory of Constitutional Genetics of Frequent Cancers HCL-CLB; Molecular Biology Platform; Léon Bérard Comprehensive Cancer Center, Lyon, France.

Up to 10% of cancers occur through the inherited mutation of a group of genes called cancer predisposition genes. Individuals who carry a mutant allele of these genes have an increased susceptibility to cancer. A growing number of cancer susceptibility genes are being identified, and the physiopathology of germline mutation-based cancer development is also being elucidated with accumulating clinical and molecular data. Read More

Best Pract Res Clin Endocrinol Metab 2015 Aug 5;29(4):633-45. Epub 2015 May 5.

INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.

Aldosterone plays an essential role in the maintenance of fluid and electrolyte homeostasis in the distal nephron. Monogenic forms of mineralocorticoid hypertension result from genetic defects leading to excessive production of aldosterone (or other mineralocorticoids) from the adrenal cortex or to illegitimate mineralocorticoid effects in the kidney. They are characterized in the majority of cases by early onset, severe or resistant hypertension and associated with suppressed renin levels. Read More

Redox Biol 2015 Dec 1;6:226-39. Epub 2015 Aug 1.

The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

Sickle cell disease and β-thalassaemia are inherited haemoglobinopathies resulting in structural and quantitative changes in the β-globin chain. These changes lead to instability of the generated haemoglobin or to globin chain imbalance, which in turn impact the oxidative environment both intracellularly and extracellularly. The ensuing oxidative stress and the inability of the body to adequately overcome it are, to a large extent, responsible for the pathophysiology of these diseases. Read More

Biomed Res Int 2015 27;2015:460190. Epub 2015 Jul 27.

Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy ; Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.

Liver fat accumulation generally related to systemic insulin resistance characterizes nonalcoholic fatty liver disease (NAFLD), which in the presence of nonalcoholic steatohepatitis (NASH) can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease in Western countries. Epidemiological, familial, and twin studies provide evidence for a strong genetic component of NAFLD susceptibility. Read More

Adv Neonatal Care 2015 Aug;15(4):241-7; quiz E1-2

Division of Genetics and Metabolism, Children's National Health System, Washington, District of Columbia.

Background: Inherited metabolic disorders (IMDs) are individually rare but collectively common disorders that frequently require rapid or urgent therapy.

Purpose: This article provides a generalized approach to IMDs, as well as some investigations and safe therapies that may be initiated pending the metabolic consult.

Methods/search Strategy: An overview of the research supporting management strategies is provided. Read More

Redox Biol 2015 Dec 17;6:135-56. Epub 2015 Jul 17.

Conway Institute, University College Dublin, Dublin, Ireland. Electronic address:

Maintaining the redox balance between generation and elimination of reactive oxygen species (ROS) is critical for health. Disturbances such as continuously elevated ROS levels will result in oxidative stress and development of disease, but likewise, insufficient ROS production will be detrimental to health. Reduced or even complete loss of ROS generation originates mainly from inactivating variants in genes encoding for NADPH oxidase complexes. Read More

Atherosclerosis 2015 Aug 9;241(2):597-606. Epub 2015 Jun 9.

Department of Vascular Medicine, Academic Medical Center, The Netherlands. Electronic address:

In this review, we discuss the screening and treatment of familial hypercholesterolemia (FH), an autosomal dominant inherited disease, characterized by severely increased levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary heart disease (CHD). Genetic family based cascade screening for FH was shown to be cost-effective and a screening program with such an approach was carried out in the Netherlands from 1994 to 2014. Over 64,000 persons have participated in this program of whom 40. Read More

J Pediatr Hematol Oncol 2015 Jul;37(5):335-43

Department of Hematology/Oncology, University Children's Hospital Basel, Basel, Switzerland.

Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by congenital abnormalities and chromosomal breakages with the occurrence of hematological and solid malignancies. FA is the most common type of inherited bone marrow failure and poses tremendous challenges. FA patients are uniquely hypersensitive to hematopoietic stem cell transplantation (HSCT) conditioning agents due to the underling chromosomal instability. Read More

Brain 2015 Mar 29;138(Pt 3):517-39. Epub 2015 Jan 29.

4 Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient's 'multiple sclerosis-like' phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Read More

Biochim Biophys Acta 2015 Sep 22;1854(9):1212-9. Epub 2015 Jan 22.

Department of Life Sciences and Reproduction, Section of Biological Chemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy. Electronic address:

Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1. Read More

J Inherit Metab Dis 2015 Jan 21;38(1):19-40. Epub 2014 Nov 21.

Department of Neurology, Neurometabolic Unit, Hospital Sant Joan de Déu and CIBERER, ISCIII, Barcelona, Spain,

Over one hundred diseases related to inherited defects of complex lipids synthesis and remodeling are now reported. Most of them were described within the last 5 years. New descriptions and phenotypes are expanding rapidly. Read More

Clin Genet 2015 Jun 9;87(6):507-16. Epub 2014 Dec 9.

Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy.

Founder mutations in specific populations are common in several Mendelian disorders. They are shared by apparently unrelated families that inherited them from a common ancestor that existed hundreds to thousands of years ago. They have been proven to impact in molecular diagnostics strategies in specific populations, where they can be assessed as the first screening step and, if positive, avoid further expensive gene scanning. Read More

J Genet Couns 2014 Dec 20;23(6):910-21. Epub 2014 Sep 20.

Bone Marrow Transplantation Program, University of Minnesota Medical Center Fairview, Minneapolis, MN, 55455, USA,

Fanconi anemia (FA) is the most common of the inherited bone marrow failure syndromes with an incidence of approximately 1/100,000 to 1/200,000 live births. FA is a genetically complex and phenotypically heterogeneous condition involving birth defects, bone marrow failure, and cancer predisposition. This rare disease became well known in the genetic counseling community in 2002, when it was identified that biallelic mutations in BRCA2 can cause FA. Read More

S Afr Med J 2014 Apr;104(4):273-4

Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease that, if not diagnosed and treated early, can be fatal. It can present from early infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is progressive intracellular accumulation of glycogen. Read More

Hamostaseologie 2014 13;34(4):301-9. Epub 2014 Aug 13.

José Rivera, PhD., Centro Regional de Hemodonación, C/ Ronda de Garay s/n, Murcia, 30003, Spain, Tel. +34/968/34 19 90; Fax +34/968/261 91, E-mail:

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder affecting lysosome-related organelles (LRO), including dense platelet granules. HPS causes oculocutaneous hypopigmentation, bleeding diathesis and granulomatous colitis or pulmonary fibrosis. To date, there is no curative treatment and the clinical management depends on the severity of symptoms. Read More

Paediatr Drugs 2014 Aug;16(4):275-91

Molecular Neurosciences, Developmental Neurosciences Programme, Institute of Child Health, University College London, London, UK.

Childhood neurotransmitter disorders are increasingly recognised as an expanding group of inherited neurometabolic syndromes. They are caused by disturbance in synthesis, metabolism, and homeostasis of the monoamine neurotransmitters, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine neurotransmission will lead to neurological symptoms that often overlap with clinical features of other childhood neurological disorders (such as hypoxic ischaemic encephalopathy, cerebral palsy, other movement disorders, and paroxysmal conditions); consequently, neurotransmitter disorders are frequently misdiagnosed. Read More

Expert Opin Investig Drugs 2014 Sep 8;23(9):1239-51. Epub 2014 Jul 8.

Amyloidosis Research and Treatment Center, IRCCS Fondazione Policlinico San Matteo , Viale Golgi, 19, 27100 Pavia , Italy.

Introduction: Transthyretin (TTR)-related hereditary amyloidosis is an adult-onset, dominantly inherited, systemic neurodegenerative disease endemic in some populations. Stabilization of the native structure of TTR by small-molecule ligands has recently proved effective in slowing neurological progression. Two drugs, tafamidis and diflunisal, are now available for most patients, particularly in the early stage of the disease. Read More