Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase.

Velaglucerase alfa is a glucocerebrosidase produced by gene activation technology in a human fibroblast cell line (HT-1080), and it is indicated as an enzyme replacement therapy (ERT) for the treatment of Gaucher disease type 1 (GD1). This multicenter, open-label, 12-month study examined the safety and efficacy of velaglucerase alfa in patients with GD1 previously receiving imiglucerase. Eligible patients, ≥2 years old and clinically stable on imiglucerase therapy, were switched to velaglucerase alfa at a dose equal to their prior imiglucerase dose.

Clinic-based infant screening for duchenne muscular dystrophy: a feasibility study.

Purpose. The purpose of this study was to assess the desirability of Duchenne muscular dystrophy (DMD) screening, the effectiveness of the consent process, and the feasibility of conducting DMD screening in a pediatric office. Methods.

Source document verification in the Mucopolysaccharidosis Type I Registry.

PURPOSE: The Mucopolysaccharidosis Type I (MPS I) Registry is an international observational database that tracks the natural history and the outcomes of patients with MPS I. The Registry was a regulatory requirement following the approval of laronidase enzyme replacement therapy for MPS I in 2003. All data are collected voluntarily after informed consent from the patient or family.

Safety of extended treatment with sapropterin dihydrochloride in patients with phenylketonuria: results of a phase 3b study.

Background: Phenylketonuria (PKU) results from impaired breakdown of phenylalanine (Phe) due to deficient phenylalanine hydroxylase (PAH) activity. Sapropterin dihydrochloride (sapropterin, Kuvan®) is the only US- and EU-approved pharmaceutical version of naturally occurring 6R-BH(4), the cofactor required for PAH activity. Sapropterin enhances residual PAH activity in sapropterin-responsive PKU patients and, in conjunction with dietary management, helps reduce blood Phe concentrations for optimal control.

Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes.

Four unrelated families with the same unbalanced translocation der(4)t(4;11)(p16.2;p15.4) were analyzed.

Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability.

Background: Cerebral palsy is a heterogeneous group of neurodevelopmental brain disorders resulting in motor and posture impairments often associated with cognitive, sensorial, and behavioural disturbances. Hypoxic-ischaemic injury, long considered the most frequent causative factor, accounts for fewer than 10% of cases, whereas a growing body of evidence suggests that diverse genetic abnormalities likely play a major role.

Methods And Results: This report describes an autosomal recessive form of spastic tetraplegic cerebral palsy with profound intellectual disability, microcephaly, epilepsy and white matter loss in a consanguineous family resulting from a homozygous deletion involving AP4E1, one of the four subunits of the adaptor protein complex-4 (AP-4), identified by chromosomal microarray analysis.

Maternal and neonatal vitamin B12 deficiency detected through expanded newborn screening--United States, 2003-2007.

The incidence of neonatal vitamin B12 (cobalamin) deficiency because of maternal deficiency was determined by surveying state newborn screening programs. Thirty-two infants with nutritional vitamin B12 deficiency were identified (0.88/100,000 newborns).

Social-adaptive and psychological functioning of patients affected by Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients.

Newborn screening for genetic disorders.

Newborn screening has become an integral part of the evaluation of more than 4 million newborns a year in the United States and of most newborns in industrialized countries and many in developing countries. Because the term "newborn screening" refers to many procedures performed in a nursery such as screening for hearing loss or congenital heart disease, this discussion is limited to screening for genetic or congenital disorders with blood spotted on filter paper cards. This discussion reflects primarily the experiences and current status of NBS programs in the United States.

High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH.

Ornithine transcarbamylase (OTC) deficiency is an X-linked inborn error of metabolism characterized by impaired synthesis of citrulline from carbamylphosphate and ornithine. Previously reported data suggest that only approximately 80% of OTC deficiency (OTCD) patients have a mutation identified by OTC gene sequencing. To elucidate the molecular etiology in patients with clinical signs of OTCD and negative OTC sequencing, we subjected their DNA to array comparative genomic hybridization (aCGH) using a custom-designed targeted 44k oligonucleotide array.

Creating genetics-based infusion centers: a case study of two models.

In 1993, the first effective enzyme replacement therapy for a genetic disease, Ceredase (Genzyme Corporation, Cambridge, MA), was approved for use in patients with Gaucher disease. Over the next 13 years, enzyme replacement therapy became clinically available for the treatment of Fabry disease, mucopolysaccharidosis Type I, mucopolysaccharidosis Type II, mucopolysaccharidosis Type VI, and glycogen storage disease Type II. The development of enzyme replacement therapy to treat lysosomal storage diseases has resulted in an increasing number of genetic patients undergoing weekly or biweekly intravenous enzyme replacement therapy and an expanded role of the genetics team to include comprehensive care involving therapeutic intervention for lysosomal storage diseases.

Heparin cofactor II-thrombin complex: a biomarker of MPS disease.

The mucopolysaccharidoses are a group of lysosomal storage disorders caused by defects in the degradation of glycosaminoglycans. Each disorder is characterized by progressive multi-system disease with considerable clinical heterogeneity. The clinical heterogeneity of these disorders is thought to be related to the degree of the metabolic block in glycosaminoglycan degradation which in turn is related to the underlying mutation at the respective locus.

Diagnosis of Fabry disease via analysis of family history.

Fabry disease is an X-linked lysosomal storage condition caused by a deficiency of alpha-galactosidase A. In order to determine the average number of family members who are diagnosed with Fabry disease following the diagnosis of a proband, four lysosomal storage disease centers across the United States reviewed the completed pedigrees of their Fabry disease patients. In addition, data from three Fabry disease families from other centers were submitted by patients directly.

X-linked fetal cardiomyopathy caused by a novel mutation in the TAZ gene.

Objectives: Mutations in the tafazzin (TAZ) gene at chromosomal locus Xq28 are responsible for Barth syndrome (BTHS), X-linked endocardial fibroelastosis (EFE), X-linked fatal infantile dilated cardiomyopathy (CMD3A), and familial isolated noncompaction of left ventricular myocardium (INVM). This evaluation was performed to determine if a known familial TAZ gene mutation might present with abnormal fetal cardiac pathology findings as early as the second trimester of pregnancy.

Methods: Prenatal diagnosis revealed that a male fetus was positive for a known familial arg94his TAZ gene mutation.

Mosaic trisomy 4: Long-term outcome on the first reported liveborn.

In a previous report, we described the first liveborn with trisomy 4 mosaicism [Marion et al. (1990) Am J Med Genet 37:362-365]. To our knowledge, since our original report, there have been only four additional reports of a prenatal diagnosis of mosaic trisomy 4 resulting in a liveborn child [Hsu et al.

Long-term developmental outcomes of children identified through a newborn screening program with a metabolic or endocrine disorder: a population-based approach.

Objective: To conduct surveillance of the developmental status of children who screen positive and are diagnosed with a metabolic or endocrine disorder.

Study Design: The Centers for Disease Control and Prevention linked three data sources in Georgia: (1) Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP), (2) Special Education Database of Metropolitan Atlanta (SEDMA), and (3) State of Georgia Newborn Blood-Spot Screening Program (NBSP).

Results: When MADDSP and NBSP were linked (birth cohorts 1981-1991), of an estimated 147 infants who screened positive for a metabolic or endocrine disorder and were at risk for mental retardation if left untreated, only three children were identified with mental retardation.

A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population.

Objectives: Although several studies describe the 22q11.2 deletion, population-based data are scant. Such data are needed to evaluate properly the impact, distribution, and clinical presentation of the deletion in the population.

Barriers to successful dietary control among pregnant women with phenylketonuria.

Purpose: The teratogenic effects of maternal PKU are preventable, yet affected babies continue to be born. This study's purpose was to identify barriers to successful dietary control among pregnant women with PKU.

Methods: An interview-based study was conducted of women with PKU who were known to metabolic disease clinics in three states and pregnant during 1998 to 2000.

Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review.

Medium chain acyl-CoA dehydrogenase (MCAD) is a tetrameric flavoprotein essential for the beta-oxidation of medium chain fatty acids. MCAD deficiency (MCADD) is an inherited error of fatty acid metabolism. The gene for MCAD is located on chromosome one (1p31).