Holoprosencephaly and low molecular weight proteinuria: The human homologue of murine megalin deficiency

We encountered a child with holoprosencephaly, pulmonary insufficiency, abs ent circulating vitamin D metabolites, mild albuminuria, and urinary excret ion of vitamin D-binding protein. The child displayed a phenotype highly re miniscent of that observed in mice genetically deficient for megalin, a mem ber of the low-density lipoprotein receptor superfamily. Only the Guthrie c ard was available from the child; the DNA sufficed for a limited haplotype analysis. We were not able to implicate the megalin gene locus directly; ho wever, the possibility of a functional megalin defect in this child remains . To the best of our knowledge, this patient represents the first report th at pathologic abnormalities consistent with megalin deficiency are present in humans. (C) 2001 by the National Kidney Foundation, Inc.