Seventeen partially
biotinidase-deficient patients detected by neonatal screening or family studies were compared with four patients with classical
biotinidase deficiency. Using a sensitive HPLC method for
biotinidase in plasma (substrate:
biocytin) the patients could be divided into two groups: one with residual
biotinidase activity, and the second with undetectable
biotinidase activity (0-activity).
Biocytin excretion, characteristically elevated in 0-activity patients, decreased rapidly with increasing residual
biotinidase activity and was almost normal when residual activity exceeded 2-3% of mean normal. In one patient with classical disease (0-activity)
biotin deficiency, typical organic aciduria and
multiple carboxylase deficiency were found as early as at the second week of life. In contrast, 13 infants with residual activities from 1.2% to 23% had no remarkable clinical or biochemical abnormalities. However, in three 5-, 14- and 15-year-old healthy siblings with residual
biotinidase activities between 2.3% and 4.2%,
biotin deficiency was proven by decreased activities of the mitochondrial carboxylases in lymphocytes (30-57% of mean normal) and, in the older siblings, also by subnormal plasma
biotin concentrations. In
biotinidase deficiency,
biotin depletion presumably occurs earlier in the brain than in other tissues and may thus first affect the central nervous system. For this reason and because of discrete biochemical abnormalities found in a patient with residual
biotinidase activity of 8%, we suggest that at least all patients with residual activities below 10% should be treated with
biotin.