Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6.

Spontaneous pathologic arterial calcifications in childhood can occur in generalized arterial calcification of infancy (GACI) or in pseudoxanthoma elasticum (PXE). GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. However, the genetic basis in subsets of both disease phenotypes remains elusive.

A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient.

In the cblF defect of vitamin B(12) (cobalamin) metabolism, cobalamin is trapped in lysosomes. Consequently, cobalamin coenzyme synthesis is blocked, and cofactors for methionine synthase and methylmalonyl-coenzyme A (CoA) mutase are deficient. We recently identified LMBRD1 as the causative gene located on chromosome 6q13 and showed that 18 out of 24 alleles in unrelated patients carried the deletion c.

Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy.

Background: Generalized arterial calcification of infancy has been reported to be frequently lethal, and the efficiency of any therapy, including bisphosphonates, is unknown. A phosphate-poor diet markedly increases survival of NPP1 null mice, a model of generalized arterial calcification of infancy.

Methods And Results: We performed a multicenter genetic study and retrospective observational analysis of 55 subjects affected by generalized arterial calcification of infancy to identify prognostic factors.

Functional consequences of mitochondrial DNA deletions in human skin fibroblasts: increased contractile strength in collagen lattices is due to oxidative stress-induced lysyl oxidase activity.

Deletions within the mitochondrial DNA (mtDNA) are thought to contribute to extrinsic skin aging. To study the translation of mtDNA deletions into functional and structural changes in the skin, we seeded human skin fibroblasts into collagen gels to generate dermal equivalents. These cells were either derived from Kearns-Sayre syndrome (KSS) patients, who constitutively carry large amounts of the UV-inducible mitochondrial common deletion, or normal human volunteers.

Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism.

Vitamin B(12) (cobalamin) is essential in animals for metabolism of branched chain amino acids and odd chain fatty acids, and for remethylation of homocysteine to methionine. In the cblF inborn error of vitamin B(12) metabolism, free vitamin accumulates in lysosomes, thus hindering its conversion to cofactors. Using homozygosity mapping in 12 unrelated cblF individuals and microcell-mediated chromosome transfer, we identified a candidate gene on chromosome 6q13, LMBRD1, encoding LMBD1, a lysosomal membrane protein with homology to lipocalin membrane receptor LIMR.