Neonatal severe primary hyperparathyroidism and alkaptonuria in a boy born to related parents with familial hypocalciuric hypercalcemia.
We describe a study of a boy with neonatal severe primary hyperparathyroidism (NSPHP) and alkaptonuria born to related parents of Turkish origin. The clinical and chemical courses (e.g. of mineral metabolism, of urinary excretion of amino acids and collagen metabolites) in response to various therapeutic approaches including total parathyroidectomy (PTX) are reported. Urinary excretion of calcium was unusually low before and immediately after PTX, and later during an inadvertent vitamin D intoxication. It corresponded to values typical for patients with familial hypocalciuric hypercalcemia (FHH), an autosomal dominant disorder. Both parents and one sibling had episodes of hypercalcemia with inappropriately high parathormone levels; in the father there was also relative hypocalciuria consistent with FHH. On the basis of the genetic and pathophysiologic data reported here, we speculate that homozygosity for the 'FHH-gene' is the cause of the life-threatening manifestation of NSPHP, whereas heterozygosity for the same gene leads to FHH, by comparison a mild disorder. The association of the two very rare recessively transmitted disorders, alkaptonuria and NSPHP, is unique; close linkage of the two genes, one coding for homogentisic acid oxidase, the other for the unknown gene product defective in NSPHP, can be suspected.