Endocrine Abstracts

Vitamin-D binding protein (VDBP) is the main reservoir of circulating vitamin D and its metabolites in blood. VDBP deficiency leads to a benign phenotype of undetectable vitamin D in the blood without remarkable effects in the calcium and bone metabolism if dietary vitamin D is sufficient ((Safadi et al 1999, Banerjee et al 2021)). This paradoxical phenotype is probably explained by the free-hormone hypothesis, which suggest that only the unbound vitamin D fraction has biological effects. Besides the null mouse model, to date only three cases of patients with verified DBP deficiency have been described in the literature. Here we present a case of a 33-year-old man adopted from India, with undetectable vitamin D, despite intramuscular injection of 100.000 IE cholecalciferol every 6 weeks, normocalcemia, and reversible mild hyperparathyroidism. Besides two finger fractures at an early age, no other fractures occurred later in life. He has a progressing osteopenia, which can be at least partially attributed to treatment with supraphysiological doses of corticosteroids due to minimal change disease-nephrotic syndrome with preserved eGFR, severe food allergies, treatment of iatrogenic adrenal insufficiency and newly diagnosed Crohn’s disease. Other factors that might have contributed to osteopenia were lactose intolerance with restricted dietary calcium intake and secondary hypogonadism with marginally reduced testosterone levels. Genetic analysis of the GC gene, encoding VDBP, revealed a homozygous pathogenic frame shift variant (c.1238del) in exon 11, which leads to a premature stop codon and probably a non-functional protein. In this 33-year-old male patient with apparently treatment resistant vitamin D deficiency we present a novel homozygous pathogenic variant in VDBP. This is line with three previously described cases with different mutations in VDBP all with undetectable levels of VDBP. Taken together, these cases highlight the importance to recognize this condition in patients with ‘;intractable’; vitamin D deficiency.