Neonatal screening for profound
biotinidase deficiency (less than 10% of the mean normal activity level) has identified a group of children with partial
biotinidase deficiency (10% to 30% of mean normal activity). Because partial
biotinidase deficiency may result in clinical consequences that may be prevented by treatment with
biotin, we evaluated such individuals and their family members (1) to determine whether partial
biotinidase deficiency is associated with symptoms and (2) to determine the inheritance pattern. We quantified serum
biotinidase activity levels and obtained medical histories of probands, their parents and siblings, and additional family members. All children with partial deficiency were healthy at the time of diagnosis. One child, who was not initially treated with
biotin, later developed
hypotonia,
hair loss, and
skin rash, which resolved with
biotin therapy. Four adults and three children with partial
biotinidase deficiency were identified among family members of infants identified by neonatal screening. All these individuals were healthy, although one sibling had elevated urinary
lactate excretion. A fifth adult with partial deficiency, found among clinically normal adult volunteers, later showed minor symptoms that resolved after
biotin therapy. Like children with profound
biotinidase deficiency, children with partial
biotinidase deficiency are symptoms free at birth. However, the subsequent occurrence of symptoms of profound
biotinidase deficiency in some persons with partial deficiency suggests that
biotin therapy for this condition may be warranted.