Parents' decision-making in newborn screening: opinions, choices, and information needs.

Objective: Our objective was to describe how parents consider disease and test characteristics when making decisions about newborn screening.

Methods: We conducted focus groups with parents from primary care clinics and interviews of parents from a genetics clinic (total of 45 participants). Participants discussed 7 vignettes about newborn screening that we developed and refined with the assistance of an expert panel.

Ocular manifestations of Fabry disease within in a single kindred.

Background: Fabry disease is an X-linked lysosomal storage disorder that causes progressive complications within the kidneys, brain, and heart. Ocular manifestations of this disease are often present at a very young age, thereby facilitating early diagnosis, before the signs and symptoms of renal disease, stroke, or hypertrophic cardiomyopathy. Early diagnosis by the eye care provider may eventually reduce the morbidity and mortality of this disease through the institution of therapy before the development of sclerotic end organ damage.

Macroautophagy is defective in mucolipin-1-deficient mouse neurons.

Mucolipidosis type IV is a neurodegenerative lysosomal disease clinically characterized by psychomotor retardation, visual impairment, and achlorhydria. In this study we report the development of a neuronal cell model generated from cerebrum of Mcoln1(-/-) embryos. Prior functional characterization of MLIV cells has been limited to fibroblast cultures gleaned from patients.

Systematic evidence review of newborn screening and treatment of severe combined immunodeficiency.

Context: Severe combined immunodeficiency (SCID) is a group of disorders that leads to early childhood death as a result of severe infections. Recent research has addressed potential newborn screening for SCID.

Objective: To conduct a systematic review of the evidence for newborn screening for SCID, including test characteristics, treatment efficacy, and cost-effectiveness.

Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay.

NRXN1 is highly expressed in brain and has been shown recently to be associated with ASD, schizophrenia, cognitive and behavioral abnormalities, and alcohol and nicotine dependence. We present three families, in whom we identified intragenic rearrangements within NRXN1 using a clinical targeted oligonucleotide array CGH. An approximately 380 kb deletion was identified in a woman with Asperger syndrome, anxiety, and depression and in all four of her children affected with autism, anxiety, developmental delay, and speech delay but not in an unaffected child.

Functional multimerization of mucolipin channel proteins.

MCOLN1 encodes mucolipin-1 (TRPML1), a member of the transient receptor potential TRPML subfamily of channel proteins. Mutations in MCOLN1 cause mucolipidosis-type IV (MLIV), a lysosomal storage disorder characterized by severe neurologic, ophthalmologic, and gastrointestinal abnormalities. Along with TRPML1, there are two other TRPML family members, mucolipin-2 (TRPML2) and mucolipin-3 (TRPML3).

Effect of sample collection on alpha-galactosidase A enzyme activity measurements in dried blood spots on filter paper.

Background: Fabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha galactosidase A (AGAL, EC 3.2.1.

Neurologic, gastric, and opthalmologic pathologies in a murine model of mucolipidosis type IV.

Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder caused by mutations in the MCOLN1 gene, which encodes the 65-kDa protein mucolipin-1. The most common clinical features of patients with MLIV include severe mental retardation, delayed motor milestones, ophthalmologic abnormalities, constitutive achlorhydria, and elevated plasma gastrin levels. Here, we describe the first murine model for MLIV, which accurately replicates the phenotype of patients with MLIV.

Fetal fatty acid oxidation defects and maternal liver disease in pregnancy.

Objective: The objective was to evaluate the relationships between all types of fetal fatty acid oxidation defects and maternal liver disease, including acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.

Methods: This was a case-control study comparing fetal fatty acid oxidation defects to the outcome of maternal liver disease. Fifty case infants with fatty acid oxidation defects were identified, with 25 matched controls collected per case.