Expanding the clinical spectrum of MTTF mutations
We report on a de novo m.586G > A MTTF mutation in a 14 yrs old boy with non-progressive muscle weakness, myalgia, normal brain MRI, normal schooling and absent central nervous system involvement. The same m.586G > A MTTF mutation has been previously reported in a 57 yrs-old woman with a progressive neurodegenerative disorder, akinesia-rigidity, abnormal movements, dementia, and psychiatric disorder. Those two strikingly different clinical presentations emphasize the impact of either mitochondrial factors (heteroplasmy, mitotic segregation) or hitherto unknown nuclear factors on the clinical expression of...
Source: Molecular Genetics and Metabolism Reports - August 14, 2019 Category: Genetics & Stem Cells Source Type: research

Exploratory study of the effect of one week of orally administered CNSA-001 (sepiapterin) on CNS levels of tetrahydrobiopterin, dihydrobiopterin and monoamine neurotransmitter metabolites in healthy volunteers
Publication date: December 2019Source: Molecular Genetics and Metabolism Reports, Volume 21Author(s): Neil Smith, Nicola Longo, Keith Levert, Keith Hyland, Nenad BlauAbstractTetrahydrobiopterin (BH4) is a cofactor for the enzymes tyrosine hydroxylase and tryptophan hydroxylase, the rate-limiting enzymes in the production of the neurotransmitters, dopamine and serotonin, respectively, in the central nervous system (CNS). Administration of BH4 is used clinically within the management of persons with genetic BH4 deficiencies, but the BH4 molecule does not cross the blood-brain barrier sufficiently. CNSA-001 is a pharmaceutica...
Source: Molecular Genetics and Metabolism Reports - August 13, 2019 Category: Genetics & Stem Cells Source Type: research

Determining factors of the cognitive outcome in early treated PKU: A study of 39 pediatric patients
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Yvan Herenger, Emmanuelle Maes, Laurent François, Jeremy Pasco, Juliette Bouchereau, Samia Pichard, Hélène Ogier de Baulny, Manuel SchiffAbstractPhenylketonuria (PKU) is a disorder of phenylalanine metabolism, characterized by a neurotoxic phenylalanine (Phe) accumulation, and treatable with a life-long Phe-restricted diet. Though early and continuously treated PKU (ETPKU) patients exhibit normal IQ, their cognitive outcome remains suboptimal. In this longitudinal study, we aimed at assessing the dete...
Source: Molecular Genetics and Metabolism Reports - July 27, 2019 Category: Genetics & Stem Cells Source Type: research

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan; 2nd report QOL survey
ConclusionOur findings supported one of the stated benefits of bezafibrate in improving QOL for patients with FAODs. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - July 25, 2019 Category: Genetics & Stem Cells Source Type: research

Future clinical and biochemical predictions of Fabry disease in females by methylation studies of the GLA gene
In this report, we summarized 36 heterozygous females with a clinical severity score based on the FAbry STabilization indEX (FASTEX). We measured their α-gal A activity and plasma/ serum globotriaosylsphingosine (lyso-Gb3) accumulation and performed electron microscopy of skin biopsies. We analyzed the methylation-sensitive restriction enzyme sites throughout the GLA gene, including the 5’UTR, and found a single SacII site and multiple HhaI and HpaII sites aggregated in exon 1 and the 5’UTR. One HpaII sequence in exon 7 was also detected as a methylation-sensitive site. With methylation-sensitive restrict...
Source: Molecular Genetics and Metabolism Reports - July 25, 2019 Category: Genetics & Stem Cells Source Type: research

Response to Gurevich and colleagues: The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: a systematic literature review by a European panel of experts
Publication date: Available online 22 July 2019Source: Molecular Genetics and Metabolism ReportsAuthor(s): Dominique P. Germain, Bruno Falissard, Max J. Hilz, Marco Spada, Christoph Wanner, Perry M. Elliott (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - July 23, 2019 Category: Genetics & Stem Cells Source Type: research

The migalastat GLP-HEK assay is the gold standard for determining amenability in patients with Fabry disease
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Raphael Schiffmann, Daniel G. Bichet, Elfrida Benjamin, Xiaoyang Wu, Roberto Giugliani (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - July 19, 2019 Category: Genetics & Stem Cells Source Type: research

Genotype-phenotype correlation of gangliosidosis mutations using in silico tools and homology modeling
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Li Ou, Sarah Kim, Chester B. Whitley, Jeanine R. Jarnes-UtzAbstractGangliosidoses, including GM1-gangliosidosis and GM2-gangliosidosis (Tay-Sachs disease and Sandhoff disease), are lysosomal disorders resulting from enzyme deficiencies and accumulation of gangliosides. Phenotypes of gangliosidoses range from infantile, late-infantile, juvenile, and to the adult form. The genotype-phenotype correlation is essential for prognosis and clinical care planning for patients with a gangliosidosis condition. Previously, we have de...
Source: Molecular Genetics and Metabolism Reports - July 18, 2019 Category: Genetics & Stem Cells Source Type: research

Very rare condition of multiple Gaucheroma: A case report and review of the literature
ConclusionGaucheroma is a rare condition in regularly treated GD patients. This patient showed poor response to doubled ERT doses. The imaging studies are necessary for Gaucher patients to detect Gaucheroma and determine their malignancy. Regular checkups are recommended in all GD patients even with ERT treatment, due to the possibility of having a deteriorating change, like Gaucheroma. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - July 13, 2019 Category: Genetics & Stem Cells Source Type: research

The characterisation of pulmonary function in patients with mucopolysaccharidoses IVA: A longitudinal analysis
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Johnny J. Kenth, Gabrielle Thompson, Catherine Fullwood, Stuart Wilkinson, Simon Jones, I.A. BruceAbstractIntroductionMucopolysaccharidosis (MPS) type IVA is a rare, autosomal recessive lysosomal storage disease causing substrate accumulation in various organs and tissues. MPS IVA is associated with both obstructive and restrictive airway disease, with the former often resulting in sleep disordered breathing (SDB). Respiratory failure is a primary cause of death in this condition. The aim of this study was to characterise...
Source: Molecular Genetics and Metabolism Reports - July 12, 2019 Category: Genetics & Stem Cells Source Type: research

Fractal genetics and heterogeneous phenotypes of mitochondrial disease require appropriate logistics of managing network structures
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Josef Finsterer (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - July 6, 2019 Category: Genetics & Stem Cells Source Type: research

Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD
ConclusionsThe use of D/L-βHBA in the therapy of severe MADD could be a good addition to the use of classical ketone body salts. The observed gastrointestinal side effects were of a mild nature and could not be specifically attributed to the D/L-βHBA treatment. In short-term application, no clinical benefit and no substantial increase of D-βHB in serum were noted. No tendency towards acidosis or alkalosis was observed during the entire period of treatment. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - June 30, 2019 Category: Genetics & Stem Cells Source Type: research

Reversal of life-threatening hepatopulmonary syndrome in Gaucher disease by imiglucerase enzyme replacement therapy
We describe a splenectomized patient with Gaucher disease who developed massive hepatomegaly, cirrhosis of the liver and life-threatening hepatopulmonary syndrome. Treatment with Imiglucerase enzyme replacement therapy resulted in dramatic reversal of hepatopulmonary syndrome and liver disease. Our report suggests that Gaucher disease pathology involving advanced fibrosis and life-threatening complications can be reversed by imiglucerase enzyme therapy.SynopsisEffect of imiglucerase enzyme replacement therapy on Hepatopulmonary Syndrome in Gaucher Disease. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - June 30, 2019 Category: Genetics & Stem Cells Source Type: research

A longitudinal study of neurocognition and behavior in patients with Hurler-Scheie syndrome heterozygous for the L238Q mutation
ConclusionL238Q patients demonstrate severe neurocognitive and neurobehavioral deficits but are relatively stable. Like the comparison group, decreasing visual spatial memory and attention and increasing anxiety suggest more intervention in life skills and emotional social supports are needed. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - June 28, 2019 Category: Genetics & Stem Cells Source Type: research

Characterization of a novel pathogenic variant in the FECH gene associated with erythropoietic protoporphyria
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Michele C. Kieke, Jacob Klemm, Arthur Rech Tondin, Victor Alencar, Nathan Johnson, Ashley M. Driver, Thomas Lentz, Gregory J. Fischer, Diane A. Caporale, Luke J. DruryAbstractErythropoietic protoporphyria (EPP) is an autosomal recessive deficiency in heme biosynthesis due to pathogenic variants in the ferrochelatase gene (FECH). Patients present with lifelong photosensitivity and potential liver disease. Here we report a novel FECH variant designated c.904_912+1del found in trans with the c.315-48T>C hypomorphic varian...
Source: Molecular Genetics and Metabolism Reports - June 27, 2019 Category: Genetics & Stem Cells Source Type: research

Late-onset Pompe disease manifests in the brain
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Josef Finsterer (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - June 22, 2019 Category: Genetics & Stem Cells Source Type: research

The mouse curly whiskers (cw) mutations are recessive alleles of hephaestin-like 1 (Hephl1)
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Sidney Eragene, Jachius J. Stewart, Juan I. Samuel-Constanzo, Taotao Tan, Nia-Zaire Esgdaille, Krista J. Bigiarelli, Vanele D. DaCosta, Henry Jimenez, Thomas R. KingAbstractThe spontaneous, curly whiskers mutation (abbreviated cw) generates kinky, brittle vibrissae in homozygous mice. Although cw has been mapped to the centromeric end of mouse Chromosome 9, no particular gene has been causally implicated, and this lack of genetic assignment has stymied cw's complete molecular and functional analysis. As a foundation for i...
Source: Molecular Genetics and Metabolism Reports - June 21, 2019 Category: Genetics & Stem Cells Source Type: research

Single-center experience with Beta-propeller protein-associated neurodegeneration (BPAN); expanding the phenotypic spectrum
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Marisa Chard, Juan Pablo Appendino, Luis E. Bello-Espinosa, Colleen Curtis, Jong M. Rho, Xing-Chang Wei, Walla Al-HertaniAbstractBeta-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation (NBIA) that presents with childhood developmental delay (especially speech delay), occasionally associated with epileptic encephalopathy, autism, or Rett-like syndrome. The majority of children described to date have been severely affected, with little to no expressive speech...
Source: Molecular Genetics and Metabolism Reports - June 21, 2019 Category: Genetics & Stem Cells Source Type: research

Kidney microRNA profile in pregnant mice reveals molecular insights into kidney adaptation to pregnancy: A pilot study
In this study, miRNome profiling suggested differential expression of 163 miRNAs (of 887 miRNAs detected) in the kidneys from pregnant mice at 6.5 days gestation when compared to non-pregnant female mice, of which 35 and 128 miRNAs were potentially down- and up-regulated, respectively. We performed network and pathway analyses of the>1700 potential mRNA targets of the differentially expressed miRNAs using MiRNet, Gene Ontology, Reactome and KEGG analyses. The mRNA targets were over-represented in numerous cellular signalling pathways, including cellular protective responses. In addition, we explored 13 and 29 potentia...
Source: Molecular Genetics and Metabolism Reports - June 19, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical outcome of a patient with lysosomal acid lipase deficiency and first results after initiation of treatment with Sebelipase alfa: A case report
We report on a case of very rare autosomal recessive cholesteryl ester storage disease due to lysosomal acid lipase deficiency (LALD). LALD is caused by mutations in the lysosomal acid lipase A (LIPA) gene resulting in cholesteryl ester accumulation in liver, spleen, and macrophages. It can lead to liver failure, accelerated atherosclerosis and premature death. Until recently, treatment options were limited to lipid-lowering medications to control dyslipidemia. Presently, a long-term enzyme replacement therapy with Sebelipase alfa, a recombinant human lysosomal acid lipase, is available for patients with LALD.Our patient's...
Source: Molecular Genetics and Metabolism Reports - June 19, 2019 Category: Genetics & Stem Cells Source Type: research

ERT impact on left ventricular mass in Fabry disease
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Alberto Ortiz (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - June 15, 2019 Category: Genetics & Stem Cells Source Type: research

D-2-hydroxyglutaric aciduria in a patient with speech delay due to a novel homozygous deletion in the D2HGDH gene
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): E. Phillips, F. Sasarman, D.S. Sinasac, W. Al-HertaniAbstractD-2-hydroxyglutaric aciduria is a rare neurometabolic condition with a variable clinical spectrum. Here we report on a patient with speech delay, ascertained for an elevated urine 2-hydroxyglutaric acid levels, and found to have a novel pathogenic homozygous deletion in D2HGDH (NG_012012.1(NM_152783.4):c.(292 + 1_293–1)_(*847_?)del). This case expands on the reported phenotype, with speech delay being the prominent clinical finding and despite identify...
Source: Molecular Genetics and Metabolism Reports - June 15, 2019 Category: Genetics & Stem Cells Source Type: research

Disease progression of alpha-mannosidosis and impact on patients and carers – A UK natural history survey
ConclusionsThis survey confirmed the heterogeneity of alpha-mannosidosis and the large impact of the disease and treatment on patients, carers, and families. Early diagnosis and access to treatment offers the best chance of slowing the disease progression and may provide some relief to patients and carers. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - June 9, 2019 Category: Genetics & Stem Cells Source Type: research

Prevalence of antibodies to ganglioside and Hep 2 in Gaucher, Niemann – Pick type C and Sanfilippo diseases
In this study, we investigated the presence of autoantibodies in the plasma of patients with Gaucher disease (GD; n = 6), Sanfilippo Syndrome B (SFB; n = 8) and Niemann – Pick type C disease (NPC; n = 5) before and following Miglustat treatment (n = 3). All were examined for antibodies to antigens of Hep-2 cells and antiganglioside antibodies (AGSA). No autoantibodies were detected in GD patients. 3/8 SFB patients showed only AGSA (2/3 IgM / IgG; 1/3 IgG), 3/8 only anti-Sm E/F and 2/8 showed both IgM / IgG or IgG AGSA and anti-Sm E/F. 3/5 NPC patients showed AGSA (2/3 IgM and IgG, 1/3 IgM) and one ant...
Source: Molecular Genetics and Metabolism Reports - June 4, 2019 Category: Genetics & Stem Cells Source Type: research

Effect of Ambroxol chaperone therapy on Glucosylsphingosine (Lyso-Gb1) levels in two Canadian patients with type 3 Gaucher disease
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Behshad Charkhand, Morris H. Scantlebury, Aya Narita, Ari Zimran, Walla Al-HertaniAbstractType 3 Gaucher disease (GD3) is characterized by progressive neurological features in addition to the typical systemic manifestations. Enzyme replacement therapy (ERT), the main stay treatment for Gaucher disease (GD), is not efficacious for the neurological manifestations. Ambroxol, in combination with ERT has been suggested to have potential as a promising therapy for patients with GD3. The purpose of this study is to assess the ef...
Source: Molecular Genetics and Metabolism Reports - May 19, 2019 Category: Genetics & Stem Cells Source Type: research

Selective screening for detection of mucopolysaccharidoses in Malaysia; A two-year study (2014–2016)
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Affandi Omar, Julaina A. Jalil, Norashareena M. Shakrin, Lock H. Ngu, Zabedah M. YunusAbstractIntroductionMucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of a specific lysosomal enzyme involved in glycosaminoglycans (GAGs) degradation. This enzyme deficiency leads to accumulation of GAGs in the lysosomes, resulting in organ dysfunction and enlargement. We aimed to detect cases of MPS in patients with suggestive signs and symptoms.MethodsThis was a 2-year cross-sectional study conducted d...
Source: Molecular Genetics and Metabolism Reports - May 11, 2019 Category: Genetics & Stem Cells Source Type: research

Characterization of immune response in Cross-Reactive Immunological Material (CRIM)-positive infantile Pompe disease patients treated with enzyme replacement therapy
Publication date: September 2019Source: Molecular Genetics and Metabolism Reports, Volume 20Author(s): Ankit K. Desai, Zoheb B. Kazi, Deeksha S. Bali, Priya S. KishnaniAbstractEnzyme replacement therapy (ERT) with rhGAA has improved clinical outcomes in infantile Pompe disease (IPD). A subset of CRIM-positive IPD patients develop high and sustained antibody titers (HSAT; ≥51,200) and/or sustained intermediate titer (SIT; ≥12,800 and 6 months of antibody titer data available, were included in the study. Patients were classified based on their longitudinal antibody titers into HSAT, SIT, and low titer (LT;
Source: Molecular Genetics and Metabolism Reports - May 11, 2019 Category: Genetics & Stem Cells Source Type: research

Drug screening for Pelizaeus-Merzbacher disease by quantifying the total levels and membrane localization of PLP1
The objective of this study was to identify therapeutic chemicals for PMD by quantifying the total levels and membrane localization of PLP1.MethodWe established a cell line stably expressing PLP1A243V fused with green fluorescent protein in oligodendrocyte-derived MO3.13 cells. We screened a chemical library composed of drugs approved for central nervous system disorders that increased both the total intensity of PLP1A243V in the whole cell and the cell membrane localization. We analyzed the change in the endoplasmic reticulum (ER) stress and the gene expression of candidate chemicals using a micro-array analysis. Finally,...
Source: Molecular Genetics and Metabolism Reports - May 10, 2019 Category: Genetics & Stem Cells Source Type: research

Very rare condition of multiple Gaucheroma: A case report and review of the literature
ConclusionGaucheroma is a rare condition of regularly treated GD patients. This patient even showed poor response to doubled ERT doses. The imaging studies are necessary for Gaucher patients to detect Gaucheroma and determine their malignancy. Regular checkups are recommended in all GD patients even with regular treatment, due to the possibility of having deteriorating change, like Gaucheroma. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - May 10, 2019 Category: Genetics & Stem Cells Source Type: research

Congenital lactic acidosis, cerebral cysts and pulmonary hypertension in an infant with FOXRED1 related complex 1 deficiency
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Delia Apatean, Bojana Rakic, Catherine Brunel-Guitton, Glenda Hendson, Renkui Bai, Michael A. Sargent, Pascal M. Lavoie, Millan Patel, Sylvia Stockler-IpsirogluAbstractMitochondrial complex I is encoded by 38 nuclear-encoded and 7 mitochondrial-encoded genes. FOXRED1 is one of the 13 additional nuclear genes known as assembly factors. So far, four patients have been described with complex I deficiency caused by autosomal recessive mutations in FOXRED1.Here, we report the fifth patient with FOXRED1 related complex 1 deficiency ...
Source: Molecular Genetics and Metabolism Reports - May 1, 2019 Category: Genetics & Stem Cells Source Type: research

A response to Germain, et al. The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts. Mol Genet Metab Rep Feb 6 2019
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Andrey Gurevich, Jӧrn Schenk, Hartmann Wellhoefer, Vasiliki Kalampoki (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - April 14, 2019 Category: Genetics & Stem Cells Source Type: research

Influence of genetic copy number variants of the human GLUT3 glucose transporter gene SLC2A3 on protein expression, glycolysis and rheumatoid arthritis risk: A genetic replication study
ConclusionsDespite a robust SLC2A3 gene copy number dependent phenotype, our study of large groups of rheumatoid arthritis cases and controls provides no evidence for rheumatoid arthritis disease protection in deletion carriers. These data emphasize the importance of well powered replication studies to confirm or refute genetic associations, particularly for relatively rare variants. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - April 8, 2019 Category: Genetics & Stem Cells Source Type: research

The evaluation of phenylalanine levels in Estonian phenylketonuria patients during eight years by electronic laboratory records
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Hardo Lilleväli, Karit Reinson, Kai Muru, Siret Saarsalu, Kadi Künnapas, Tiina Kahre, Ülle Murumets, Katrin ÕunapAbstractBlood phenylalanine (Phe) values from the dried blood spots of all Estonian phenylketonuria (PKU) patients have been deposited into a unified electronic laboratory database for eight years, providing an opportunity to assess the adherence of the patients to dietary recommendations over time and to observe patient practices both individually and collectively. Our results demonstrate gene...
Source: Molecular Genetics and Metabolism Reports - March 24, 2019 Category: Genetics & Stem Cells Source Type: research

Identification of an iron-responsive subtype in two children diagnosed with relapsing-remitting multiple sclerosis using whole exome sequencing
ConclusionOur findings highlight the potential value of WES to identify heritable risk factors that could affect the reabsorption of transferrin-bound iron in the kidneys causing sustained iron loss, together with inhibition of vitamin B12 absorption and vitamin D reabsorption (CUBN) and iron transport into mitochondria (SLC25A37) as the sole site of heme synthesis. This supports a model for RRMS in children with an apparent iron-deficient biochemical subtype of MS, with oligodendrocyte cell death and impaired myelination possibly caused by deficits of energy- and antioxidant capacity in mitochondria. (Source: Molecular Ge...
Source: Molecular Genetics and Metabolism Reports - March 24, 2019 Category: Genetics & Stem Cells Source Type: research

Home delivery service of low protein foods in inherited metabolic disorders: Does it help?
ConclusionsAlthough home delivery services for special LP foods are associated with less errors and delay compared with pharmacies, inaccuracies and inefficiencies still occur and the overall system is complex. We suggest a new, simpler, less fragmented system whereby metabolic dietitians prescribe LP foods. This is likely to result in less burden on NHS resources and ensure a better treatment delivered to IMD patients. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - March 23, 2019 Category: Genetics & Stem Cells Source Type: research

Pulmonary hypertension may be secondary in carriers of compound heterozygous FOXRED1 variants
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Josef Finsterer (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - March 23, 2019 Category: Genetics & Stem Cells Source Type: research

Next generation sequencing for clinical diagnostics: Five year experience of an academic laboratory
We describe the implementation of a single broad-based NGS sequencing assay to meet the genetic testing needs at the University of Minnesota. A single hybrid capture library preparation was used for each test ordered, data was informatically blinded to clinically-ordered genes, and identified variants were reviewed and classified by genetic counselors and molecular pathologists. We performed 2509 sequencing tests from August 2012 till December 2017. The diagnostic yield has remained steady at 25%, but the number of variants of uncertain significance (VUS) included in a patient report decreased over time with 50% of the pat...
Source: Molecular Genetics and Metabolism Reports - March 4, 2019 Category: Genetics & Stem Cells Source Type: research

Management of manifesting FOXRED1 carriers is complex
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 26, 2019 Category: Genetics & Stem Cells Source Type: research

A closer look at ARSA activity in a patient with metachromatic leukodystrophy
We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in a second laboratory. Measurement of arylsulfatase A in that laboratory showed a partial decrease in arylsulfatase A activity measured under typical conditions (about 37% of the normal mean). When the concentration of substrate in the assay was lowe...
Source: Molecular Genetics and Metabolism Reports - February 21, 2019 Category: Genetics & Stem Cells Source Type: research

Harderoporphyria: Case of lifelong photosensitivity associated with compound heterozygous coproporphyrinogen oxidase (CPOX) mutations
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): A. Moghe, V.M.S. Ramanujam, J.D. Phillips, R.J. Desnick, K.E. AndersonAbstractA 78-year-old man with a history of neonatal anemia and jaundice and life-long photosensitivity was found to have harderoporphyria, as evidenced by increased porphyrins in urine, plasma, erythrocytes and feces including large amounts of harderoporphyrin in feces and erythrocytes. Two previously undescribed coproporphyrinogen oxidase (CPOX) mutations were identified, including a deletion of four amino acids in a region of the enzyme mutated in 7 of th...
Source: Molecular Genetics and Metabolism Reports - February 20, 2019 Category: Genetics & Stem Cells Source Type: research

The importance of the nuclear background on the phenotypic signature caused by the MELAS m.1630 A>G variant
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Andrea Gropman, Anne Chiaramello (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 17, 2019 Category: Genetics & Stem Cells Source Type: research

Emotional experience in parents of children with Zellweger spectrum disorders: A qualitative study
This study underscores the profound emotional impact on parents who are caregivers for children with ZSDs, highlighting the utility of patient community feedback and qualitative approaches to fully characterize the overall family experience. Simple, targeted approaches focusing on improved communication between healthcare professionals and families, as well as offering resources for emotional support may greatly improve the lives of families living with ZSD and other rare pediatric diseases. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 15, 2019 Category: Genetics & Stem Cells Source Type: research

Pathogenicity of the m.1630A > G variant remains elusive if related mutation carriers with similar heteroplasmy rates are asymptomatic
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Josef Finsterer (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 13, 2019 Category: Genetics & Stem Cells Source Type: research

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts
ConclusionsERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 7, 2019 Category: Genetics & Stem Cells Source Type: research

Biomarkers in patients with mucopolysaccharidosis type II and IV
In conclusion, selected pro-inflammatory factors can be potential biomarkers in patients with MPS II and IV as well as GAGs levels. (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 7, 2019 Category: Genetics & Stem Cells Source Type: research

Defective neuronal and oligodendroglial differentiation by FTD3- and ALS17-associated Ile29-to-Val mutation of CHMP2B
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Minami Yamawaki, Masumi Akiba, Naoto Matsumoto, Natsumi Watanabe, Kohei Hattori, Yu Takeuchi, Takako Morimoto, Hiroaki Oizumi, Katsuya Ohbuchi, Yuki Miyamoto, Junji Yamauchi (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 3, 2019 Category: Genetics & Stem Cells Source Type: research

Management of Leigh syndrome due to NDUFAF6 variants
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): Josef Finsterer, Fulvio A. Scorza (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - February 1, 2019 Category: Genetics & Stem Cells Source Type: research

Benefits of prophylactic heme therapy in severe acute intermittent porphyria
We report two patients with such frequent attacks of AIP, who have been managed with prophylactic heme therapy on a weekly basis. We describe results particularly in relation to symptom control, biochemical findings, health care costs, quality of life, and utilization of resources. During 11-month duration of weekly prophylactic heme infusions, we observed a 100% decrease in acute attacks and inpatient admissions in one subject and a 75% decrease in the other. During this time, we also observed a significant decrease in the number of emergency room visits. The decrease in number of acute attacks requiring hospital admissio...
Source: Molecular Genetics and Metabolism Reports - February 1, 2019 Category: Genetics & Stem Cells Source Type: research

Feasibility of cellular bioenergetics as a biomarker in porphyria patients
In conclusion, we demonstrate that the bioenergetic profile and mitochondrial activities assessed in porphyria patients and is different than in healthy control individuals. Further, our novel preliminary findings suggest the existence of a mitochondrial dysfunction in porphyria and this may be used as potential non-invasive biomarker for disease activity. This needs to be assessed with a systematic examination in a larger patient cohort. Studies are also suggested to examine mitochondrial metabolism as basis to understand mechanisms of these findings and deriving mitochondrial based therapies for porphyria. (Source: Molec...
Source: Molecular Genetics and Metabolism Reports - January 30, 2019 Category: Genetics & Stem Cells Source Type: research

Synergistic heterozygosities beyond energy-related metabolic pathways as the mechanism of recurrent rhabdomyolysis
Publication date: June 2019Source: Molecular Genetics and Metabolism Reports, Volume 19Author(s): P. Phowthongkum (Source: Molecular Genetics and Metabolism Reports)
Source: Molecular Genetics and Metabolism Reports - January 27, 2019 Category: Genetics & Stem Cells Source Type: research