BIOTINIDASE DEFICIENCY IN JUVENILE MULTIPLE CARBOXYLASE DEFICIENCY

TY - JOUR

T1 - BIOTINIDASE DEFICIENCY IN JUVENILE MULTIPLE CARBOXYLASE DEFICIENCY

AU - Thoene, Jess

AU - Wolf, Barry

N1 - Funding Information: (achieved by withholding biotin for only 8 days) her biotin response was normal. The figure shows that at the start of the study her plasma biotin was slightly above normal range (2720 pg/ml). However, 1 h after ingestion of 5 J.lg/kg of biotin, her plasma biotin concentration rose to 5650 pg/ml, as in similarly treated biotin- replete controls. Biotin clearance was also normal (34-4 4 ml/min/1’ 73 m2). The fraction of biotin excreted in her urine in the 24 h after the biotin dose was 50’ 8%, twice as high as the amount excreted by the controls and more than three times her previous maximum excretion (15%). Biotinidase activity in the patient’s serum was undetectable (table). The mother, who does not have clinical biotin deficiency, had 46% of mean normal biotinidase activity and a plasma biotin of 248 pg/ml, which is below normal. Dietary biotin exists primarily as biotinyl groups linked to the E-amino groups of lysine residues of proteins.9 Biotinidase hydrolyses this bond, releasing free biotin. Biotinidase activity is widely distributed, particularly in liver, kidney, serum, and gut mucosa.9 Although this enzyme’s primary site of action on dietary protein is not known, deficiency could impair ability to maintain normal body stores of free biotin, leading to a hypobiotinaemic state. Whether biotinidase is also involved in the absorption of free biotin is not known. The patient’s normal plasma biotin response to the ingestion of 5pg/kg of biotin when her tissues were replete with biotin, but her failure to respond when she was biotin deficient is probably caused by rapid entry of biotin into the depleted tissues. Similar results have been obtained in thiamine-deficient patients. 10,1 Rapid saturation of deficient tissues with the vitamin results in subnormal increases in the plasma concentrations, mimicking apparent defect in intestinal absorption. Juvenile MCD probably results from impaired generation of free biotin from biotinyl residues of dietary protein. Presumably the child is born with normal stores of free biotin but, once dependent on dietary protein-bound biotin, a child with biotinidase deficiency would become hypobiotinaemic and clinical symptoms of biotin deficiency would ensue. This mechanism could account for the late onset of acute symptoms (as opposed to the neonatal onset of symptoms in holocarboxylase synthetase deficiency) and, for some of the clinical variability. We thank Robert E. Grier and Rosemary Lemons for technical assistance and Dr Herman Baker for helpful discussions. This work was supported by grants from the National Institutes of Health (AM 25675 and AM 25548), the National Foundation-March of Dimes (6-342), and the Michigan Department of Mental Health. B. W. is the recipient ofa NIH research career development award (AM 00677).

PY - 1983/8/13

Y1 - 1983/8/13

UR - http://www.scopus.com/inward/record.url?scp=0020955766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020955766&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(83)90364-1

DO - 10.1016/S0140-6736(83)90364-1

M3 - Letter

C2 - 6135890

AN - SCOPUS:0020955766

SN - 0140-6736

VL - 322

SP - 398

JO - The Lancet

JF - The Lancet

IS - 8346

ER -