0000000000547736
AUTHOR
Adelbert A. Roscher
Disease manifestations and X inactivation in heterozygous females with Fabry disease
Aim: Fabry disease is an X-linked lysosomal storage disorder characterized by an accumulation of neutral glycosphingolipids in multiple organ systems caused by α-galactosidase A deficiency due to mutations in the GLA gene. The majority of heterozygous females show the characteristic signs and symptoms of the disease, and some of them are severely affected. The current hypothesis for the occurrence of disease manifestations in females is skewed X inactivation favouring the mutant GLA allele. Method: We analyzed the patterns of X inactivation in the leukocytes of 28 biochemically and genetically characterized symptomatic Fabry disease heterozygotes and their correlation with clinical and bioc…
The four murine peroxisomal ABC-transporter genes differ in constitutive, inducible and developmental expression.
Four ATP-binding cassette (ABC) half-transporters have been identified in mammalian peroxisomes: adrenoleukodystrophy protein (ALDP), adrenoleukodystrophy-related protein (ALDRP), 70-kDa peroxisomal membrane protein (PMP70) and PMP70-related protein (P70R). Inherited defects in ALDP cause the neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). By comparative Northern blot analyses we found each of the four murine peroxisomal ABC transporter mRNA species at maximum abundance only in a few tissues, which differed for each family member. The four genes were also regulated differentially during mouse brain development: ALDP mRNA was most abundant in embryonic brain and gradually d…
Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment.
New technology enables expansion of newborn screening (NBS) of inborn errors aimed to prevent adverse outcome. In conditions with a large share of asymptomatic phenotypes, the potential harm created by NBS must carefully be weighed against benefit. Policies vary throughout the United States, Australia, and Europe due to limited data on outcome and treatability of candidate screening conditions. We elaborated the rationale for decision making in 3-methylcrotonyl-coenzyme A (CoA) carboxylase deficiency (MCCD), which afflicts leucine catabolism, with reported outcomes ranging from asymptomatic to death. In Bavaria, we screened 677,852 neonates for 25 conditions, including MCCD, based on elevat…