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

Abstract

We encountered a child with holoprosencephaly, pulmonary insufficiency, absent circulating vitamin D metabolites, mild albuminuria, and urinary excretion of vitamin D–binding protein. The child displayed a phenotype highly reminiscent of that observed in mice genetically deficient for megalin, a member of the low-density lipoprotein receptor superfamily. Only the Guthrie card was available from the child; the DNA sufficed for a limited haplotype analysis. We were not able to implicate the megalin gene locus directly; however, the possibility of a functional megalin defect in this child remains. To the best of our knowledge, this patient represents the first report that pathologic abnormalities consistent with megalin deficiency are present in humans.