Olaf A Bodamer

Boston Children's Hospital, Boston, Massachusetts, United States

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Publications (167)552.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: RASopathies are a clinically heterogeneous group of conditions caused by mutations in one of sixteen proteins in the RAS-MAPK pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and ,p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins, however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma. This article is protected by copyright. All rights reserved.
    Clinical Genetics 05/2015; DOI:10.1111/cge.12608 · 3.93 Impact Factor
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    ABSTRACT: Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Medical Genetics 03/2015; 52(6). DOI:10.1136/jmedgenet-2015-103018 · 6.34 Impact Factor
  • Molecular Genetics and Metabolism 02/2015; 114(2). DOI:10.1016/j.ymgme.2014.12.034 · 2.63 Impact Factor
  • Britt A Johnson · Angela Dajnoki · Olaf A Bodamer
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    ABSTRACT: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder due to deficiency of alpha iduronidase (IDUA). Progressive storage of dermatan and heparan sulfate throughout the body lead to a multiorgan presentation including short stature, dysostosis multiplex, corneal clouding, hearing loss, coarse facies, hepatosplenomegaly, and intellectual disability. Diagnosis of MPS I is based on IDUA enzyme analysis in leukocytes or dried blood spots (DBS) followed by molecular confirmation of the IDUA gene mutations in individuals with low enzyme activity. The advent of mass spectrometry methods for enzyme analysis in DBS has enabled high-throughput screening for MPS I in symptomatic individuals and newborn infants. The following unit provides the detailed analytical protocol for measurement of IDUA activity in DBS using tandem mass spectrometry. © 2015 by John Wiley & Sons, Inc.
    Current protocols in human genetics / editorial board, Jonathan L. Haines ... [et al.] 01/2015; 84:17.17.1-8. DOI:10.1002/0471142905.hg1717s84
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    ABSTRACT: Pompe disease (glycogen storage disease type II) is caused by autosomal recessive mutations in GAA gene. The estimated frequency of late-onset Pompe disease is around 1:60,000. However, only two infantile and one late-onset Pompe patients have been reported in Finland with a population of 5 million. We screened for late-onset Pompe disease in a cohort of undetermined myopathy patients with proximal muscle weakness and/or elevated serum creatine kinase values. Acid α-glucosidase (GAA) activity in dried blood spots was measured and clinical data collected in 108 patients. Four patients had low normal GAA activity; all the others had activities well within the normal range. Re-analyses of these patients did not reveal new Pompe patients. Our findings suggest that Pompe disease is extremely rare in Finland. Finland is an example of an isolated population with enrichment of certain mutations for genetic disorders and low occurrence of some autosomal recessive diseases.
    Neuromuscular Disorders 11/2014; 24(11). DOI:10.1016/j.nmd.2014.06.438 · 2.64 Impact Factor
  • The 64th Annual Meeting of the American Society of Human Genetics, San Diego, CA; 10/2014
  • Olaf A. Bodamer · Roberto Giugliani · Tim Wood
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    ABSTRACT: Mucopolysaccharidosis type III (MPS III) is characterized by progressive neurological deterioration, behavioral abnormalities, a relatively mild somatic phenotype, and early mortality. Because of the paucity of somatic manifestations and the rarity of the disease, early diagnosis is often difficult. Therapy targeting the underlying disease pathophysiology may offer the greatest clinical benefit when started prior to the onset of significant neurologic sequale. Here we review current practices in the laboratory diagnosis of MPS III in order to facilitate earlier patient identification and diagnosis. When clinical suspicion of MPS III arises, the first step is to order a quantitative assay that screens urine for the presence of glycosaminoglycan biomarkers using a spectrophotometric compound (e.g., dimethylmethylene blue). We recommend testing all patients with developmental delay and/or behavioral abnormalities as part of the diagnostic work-up because quantitative urine screening is inexpensive and non-invasive. Semi-quantitative urine screening assays using cationic dyes on filter paper (e.g., spot tests) have relatively high rates of false-positives and false-negatives and are obsolete. Of note, a negative urinary glycosaminoglycan assay does not necessarily rule out MPS because, in some patients, an overlap in excretion levels with healthy controls may occur. All urine samples that test positive for glycosaminoglycans with a quantitative assay should be confirmed by electrophoresis, thin layer chromatography, or tandem mass spectrometry, which further improves the sensitivity and specificity. The gold standard for diagnosis remains the enzyme activity assay in cultured skin fibroblasts, leukocytes, plasma, or serum, which can be used as a first-line diagnostic test in some regions. Molecular genetic analysis should be offered to all families of patients to allow genetic counseling for informed family planning. For a small number of variants, genotype-phenotype correlations are available and can offer prognostic value. Prenatal testing via enzyme activity assay in chorionic villi or amniotic fluid cells is available at a limited number of centers worldwide, but whenever possible, a molecular genetic analysis is preferred for prenatal diagnosis. To conclude, we discuss the development of newborn screening assays in dried blood spots and high-throughput methods for sequencing the protein-coding regions of the genome (whole exome sequencing) and their relevance to future changes in the MPS III diagnostic landscape.
    Molecular Genetics and Metabolism 09/2014; 113(1-2). DOI:10.1016/j.ymgme.2014.07.013 · 2.63 Impact Factor
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    ABSTRACT: Background: Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients. Method: A UPLC-MS/MS was used for biomarker analysis. Results: Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues. Conclusions: In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile.
    Clinica Chimica Acta 08/2014; 438. DOI:10.1016/j.cca.2014.08.002 · 2.82 Impact Factor
  • Sandra D.K. Kingma · Olaf A. Bodamer · Frits A. Wijburg
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    ABSTRACT: The lysosomal storage disorders (LSDs) are a group of genetic disorders resulting from defective lysosomal metabolism and subsequent accumulation of substrates. Patients present with a large phenotypic spectrum of disease manifestations that are generally not specific for LSDs, leading to considerable diagnostic delay and missed cases. Introduction of new disease modifying therapies for LSDs has made early diagnosis a priority. Increased awareness, but particularly the introduction of screening programs allow for early diagnosis and timely initiation of treatment. This review will provide insight into the epidemiology and diagnostic process for LSDs. In addition, challenges for carrier screening, high-risk screening and newborn population screening for LSDs are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Best Practice & Research: Clinical Endocrinology & Metabolism 08/2014; 29(2). DOI:10.1016/j.beem.2014.08.004 · 4.60 Impact Factor
  • Britt A Johnson · Angela Dajnoki · Olaf Bodamer
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    ABSTRACT: Gaucher Disease (GD) is a progressive lysosomal storage disorder caused by deficiency of glucocerebrosidase (GBA). The clinical phenotype follows a spectrum ranging from severe early-onset to milder late-onset disease. The absence of neurological involvement defines GD type I, whereas neuronopathic features define GD type II and III. Early diagnosis may be important for timely initiation of enzyme replacement therapy to prevent disease complications, although the enzyme does not cross the blood brain barrier. Diagnosis of GD can be readily achieved by analysis of GBA in leukocytes, fibroblasts, and/or dried blood spots using fluorometric, microfluidic or mass spectrometry-based assays. Low GBA activities are typically confirmed through molecular analysis of the GBA gene. GBA analysis in dried blood spots may be attractive for high-throughput screening of at-risk individuals and/or newborn infants. The method detailed in this unit is based on GBA analysis by tandem mass spectrometry following incubation of dried blood spots with the GBA-specific substrate D-glucosyl-β1-1'-N-dodecanoyl-D-erythro-sphingosine [C12-glucocerebroside (C36 H69 NO8 )] and internal standard N-myristoyl-D-erythro-sphingosine [C14-ceramide (C32 H63 NO3 )]. GBA activities in more than 2,000 newborn infants showed a mean of 22.0 ± 13.8 μmol/hr/liter (median: 19.9 μmol/hr/liter; 95% CI: 21.41-22.59 μmol/hr/liter). GBA activities in an adult population (n >1,200) showed generally lower enzyme activities than newborns, with a mean of 9.87 ± 9.35 μmol/hr/liter (median: 8.06 μmol/hr/liter). GBA activities in ten adult patients with confirmed GD were less than 4.2 μmol/hr/liter and in seven infants and children with GD less than 1.24 μmol/hr/liter. This method is robust, sensitive, and suitable for high-throughput analysis of hundreds of samples. Curr. Protoc. Hum. Genet. 82:17.15.1-17.15.6. © 2014 by John Wiley & Sons, Inc.
    Current protocols in human genetics / editorial board, Jonathan L. Haines ... [et al.] 07/2014; 82:17.15.1-6. DOI:10.1002/0471142905.hg1715s82
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    ABSTRACT: We aim to identify the link between placental histological findings and obstetric reports to determine possible risk factors of spontaneous preterm birth (SPTB). We prospectively ascertained birth records and outcomes from all deliveries in our hospital in 1 year. Records were used to determine and stratify for either full-term or preterm [spontaneous or indicated (I)] deliveries. We analyzed for risk factor association using χ(2) tests and common odds ratio estimates (SPSS v21.0). Our cohort totaled 6088 deliveries: 236 IPTB, 43 SPTB, and 5809 term births. Largely Hispanic, we determined race, parity, prenatal care access, preeclampsia, gestational diabetes, and BMI to be highly associated with SPTB (p < 0.01). Histologically, placentas of women with SPTB were twice as likely to have chronic villitis. We found that chronic villitis is associated with SPTB. Results of this study can be used in increasing the understanding of SPTB.
    Fetal and pediatric pathology 05/2014; 33(4). DOI:10.3109/15513815.2014.913749 · 0.48 Impact Factor
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    ABSTRACT: Gaucher disease, an autosomal recessive condition due to deficiency of lysosomal glucocerebrosidase, is a multisystemic disease, with variable age of onset, severity and progression. It is classified into subtypes delineated by the absence (type 1) or presence (type 2 and 3) of primary nervous system involvement.The ethnically diverse, largely immigrant population in South Florida has a spectrum of Gaucher disease phenotypes, creating a challenge for optimization of disease management and an opportunity to explore treatment patterns. Ninety-three records from patients with Gaucher type I in South Florida were retrieved from the International Collaborative Gaucher Group (ICGG) Registry. Individual genotypes were correlated with severity scores and success at achieving published therapeutic goals for haemoglobin concentration, platelet count, spleen volume, liver volume and amelioration of bone pain and bone crises. The majority of patients were diagnosed during the fifth decade of life. Almost two-thirds were homozygous for the N370S mutation, reflecting the large Ashkenazi Jewish population in South Florida. The majority received imiglucerase (62.8%) at various intervals. 24.5% of patients underwent splenectomy before starting enzyme replacement therapy. After a median 12 treatment years, South Florida patients matched or exceeded the ICCG 4 year therapeutic goal achievement for platelet count (85.4% vs. 79.6% success), spleen volume (93.3% vs. 78.0% success), liver volume (93.4% vs. 90.6% success), and bone crises (100% vs. 99% success). Nevertheless, fewer patients with intact spleens had sustained achievement of all 6 therapeutic goals (30.4% versus 41.4%) and only 40% of the splenectomy patients sustained achievement of 5/5 possible goals. 54.7% of the intact spleen patients continued to have bone pain vs. 29.8% in ICCG. Significantly, only 37% of the ICGG patient cohort had bone pain prior to initiation of treatment compared to 73.4% of the South Florida patients (moderate or severe pain in 59.6%). Demographic characteristics are a significant determinant of the differences in response to treatment observed in South Florida Gaucher patients compared to those described in the international population enrolled in the ICGG Gaucher Registry. Individual genotypes and ethnic background are important considerations for optimizing patient care for Gaucher disease.
    Orphanet Journal of Rare Diseases 03/2014; 9(1):45. DOI:10.1186/1750-1172-9-45 · 3.36 Impact Factor
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    ABSTRACT: New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.
    Molecular Genetics and Metabolism 03/2014; 112(2). DOI:10.1016/j.ymgme.2014.02.013 · 2.63 Impact Factor
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    ABSTRACT: The first GalT gene knockout (KO) mouse model for Classic Galactosemia (OMIM 230400) accumulated some galactose and its metabolites upon galactose challenge, but was seemingly fertile and symptom free. Here we constructed a new GalT gene-trapped mouse model by injecting GalT gene-trapped mouse embryonic stem cells into blastocysts, which were later implanted into pseudo-pregnant females. High percentage GalT gene-trapped chimera obtained were used to generate heterozygous and subsequently, homozygous GalT gene-trapped mice. Biochemical assays confirmed total absence of galactose-1 phosphate uridylyltransferase (GALT) activity in the homozygotes. Although the homozygous GalT gene-trapped females could conceive and give birth when fed with normal chow, they had smaller litter size (P=0.02) and longer time-to-pregnancy (P=0.013) than their wild-type littermates. Follicle-stimulating hormone levels of the mutant female mice were not significantly different from the age-matched, wild-type females, but histological examination of the ovaries revealed fewer follicles in the homozygous mutants (P=0.007). Administration of a high-galactose (40% w/w) diet to lactating homozygous GalT gene-trapped females led to lethality in over 70% of the homozygous GalT gene-trapped pups before weaning. Cerebral edema, abnormal changes in the Purkinje and the outer granular cell layers of the cerebellum, as well as lower blood GSH/GSSG ratio were identified in the galactose-intoxicated pups. Finally, reduced growth was observed in GalT gene-trapped pups fed with normal chow and all pups fed with high-galactose (20% w/w) diet. This new mouse model presents several of the complications of Classic Galactosemia and will be useful to investigate pathogenesis and new therapies.European Journal of Human Genetics advance online publication, 19 February 2014; doi:10.1038/ejhg.2014.12.
    European journal of human genetics: EJHG 02/2014; 22(10). DOI:10.1038/ejhg.2014.12 · 4.35 Impact Factor
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    ABSTRACT: Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.
    Journal of Inherited Metabolic Disease 12/2013; 37(3). DOI:10.1007/s10545-013-9664-5 · 3.37 Impact Factor
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    ABSTRACT: Background: Studies on the genetics of obstetrics and gynaecology have previously focused on utilizing fresh placental tissue (PT) for downstream genetic analysis. However, fresh PT would rarely be histopathologically evaluated for deep-phenotyping purposes and cannot be stored for long-term. Therefore, the use of fixed and paraffin embedded PT would be of interest due to the increasing importance for retrospective genetic studies. With the technological advancement of DNA isolation methods and next-generation sequencing, this could increase the efficiency in variant identification from the preserved PT samples. Due to the fact that the placenta contains a mix of maternal and fetal tissue, the experimental and variant identification challenges are significantly increased. Objective: We propose to isolate DNA from preserved PT and successfully perform variant identification.
    The 63rd Annual Meeting of the American Society of Human, Boston, MA; 10/2013
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    ABSTRACT: Genomic microarrays have been used as the first-tier cytogenetic diagnostic test for patients with developmental delay/intellectual disability, autism spectrum disorders and/or multiple congenital anomalies. The use of SNP arrays has revealed regions of homozygosity in the genome which can lead to identification of uniparental disomy and parental consanguinity in addition to copy number variations. Consanguinity is associated with an increased risk ofbirth defects and autosomal recessive disorders. However, the frequency of parental consanguinity in children with developmental disabilities is unknown, and consanguineouscouples may not be identified during doctor's visit or genetic counseling without microarray. We studied 607 proband pediatric patients referred for developmental disorders using a 4 x 180 K array containing both CGH and SNP probes. Using 720, 360, 180, and 90 Mb as the expected sizes of homozygosity for an estimated coefficient of inbreeding (F) 1/4, 1/8, 1/16, 1/32, parental consanguinity was detected in 21cases (3.46%). Parental consanguinity is not uncommon in children with developmental problems in our study population, and can be identified by use of a combined CGH and SNP chromosome microarray. Identification of parental consanguinity in such cases can be important for further diagnostic testing.
    Molecular Cytogenetics 09/2013; 6(1):38. DOI:10.1186/1755-8166-6-38 · 2.14 Impact Factor
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    ABSTRACT: Recently, lyso-globotriaosylsphingosine (lyso-Gb3) was found to be elevated in plasma of treatment naive male patients and some female patients with Fabry Disease (FD). This study tested whether lyso-Gb3 could be analyzed in dried blood spots (DBS) from filter cards and whether concentrations are elevated in newborn infants with FD. Lyso-Gb3 concentrations were analyzed in DBS following extraction using a novel HPLC-mass spectrometry (MS)/MS method. Lyso-Gb3 levels in DBS were above the lower limit of quantitation (0.28 ng/mL) in 5/17 newborn FD infants (16 males; range: 1.02-8.81 ng/mL), but in none of the newborn controls, in all 13 patients (4 males) with classic FD (range: 2.06-54.1 ng/mL), in 125/159 Taiwanese individuals with symptomatic or asymptomatic FD who carry the late onset α-galactosidase A (GLA) mutation c.936+919G>A (IVS4+919G>A) (3.75±0.69 ng/mL; range: 0.418-3.97 ng/mL) and in 20/29 healthy controls (0.77±0.24 ng/mL; range: 0.507-1.4 ng/mL). The HPLC-MS/MS method for analysis of lyso-Gb3 is robust and yields reproducible results in DBS in patients with FD. However, concentrations of lyso-Gb3 were below the limit of quantitation in most newborn infants with FD rendering this approach not suitable for newborn screening. In addition, most females with the late onset mutation have undetectable lyso-Gb3 concentrations.
    Annals of Laboratory Medicine 07/2013; 33(4):274-8. DOI:10.3343/alm.2013.33.4.274 · 1.48 Impact Factor
  • O. A. Bodamer
    Monatsschrift Kinderheilkunde 05/2013; 161(5):383-383. · 0.23 Impact Factor
  • Olaf A Bodamer · Britt Johnson · Angela Dajnoki
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    ABSTRACT: Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficiency of alpha galactosidase A (GLA). Progressive, intralysosomal accumulation of neutral glycosphingolipids in endothelial cells and podocytes leads to multi-organ involvement in affected males and to a lesser extent in affected females. Diagnosis of FD is based on GLA analysis in leukocytes or dried blood spots (DBS) in FD males while GLA activities may be within the normal range in FD females. The advent of fluorometric and mass spectrometry methods for enzyme analysis in DBS has simplified the diagnostic approach for FD males, facilitating high-throughput screening of at risk populations and newborn infants. However, the diagnostic mainstay for FD females remains molecular analysis of the GLA gene. The following unit will provide the detailed analytical protocol for measurement of GLA activity in DBS using tandem mass spectrometry. Curr. Protoc. Hum. Genet. 77:17.13.1-17.13.7. © 2013 by John Wiley & Sons, Inc.
    Current protocols in human genetics / editorial board, Jonathan L. Haines ... [et al.] 04/2013; Chapter 17:Unit17.13. DOI:10.1002/0471142905.hg1713s77

Publication Stats

2k Citations
552.63 Total Impact Points


  • 2015
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2011–2015
    • University of Miami Miller School of Medicine
      • • Department of Human Genetics (Dr. John T. Macdonald Foundation)
      • • Division of Clinical and Translational Genetics
      Miami, Florida, United States
  • 2012–2014
    • University of Miami
      • • Miller School of Medicine
      • • Dr. John T. Macdonald Foundation Department of Human Genetics
      كورال غيبلز، فلوريدا, Florida, United States
  • 2003–2013
    • Medical University of Vienna
      • • Department of Radiology
      • • Department of Paediatrics and Adolescent Medicine
      Wien, Vienna, Austria
  • 2009–2012
    • Paracelsus Medical University Salzburg
      Salzburg, Salzburg, Austria
    • Allgemeines Krankenhaus Linz
      Linz, Upper Austria, Austria
  • 2010–2011
    • University of Salzburg
      Salzburg, Salzburg, Austria
  • 2006–2008
    • University of Vienna
      Wien, Vienna, Austria
  • 2004–2008
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 2005–2007
    • Children´s Hospital Association
      Overland Park, Kansas, United States
  • 2003–2007
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 1998–2004
    • Baylor College of Medicine
      • Department of Molecular & Human Genetics
      Houston, Texas, United States
  • 1997
    • Philipps University of Marburg
      Marburg, Hesse, Germany