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Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy.
Eur J Pediatr. 1998 Jul; 157(7):570-5.EJ

Abstract

The clinical and biochemical findings in a family with late-onset holocarboxylase synthetase (HCS) deficiency are described. The index patient had two life-threatening episodes of metabolic decompensation at the age of 13 and 18 months with ketotic hypoglycaemia, vomiting and progressive loss of consciousness. The child recovered without biotin therapy. Organic aciduria characteristic of multiple carboxylase deficiency (MCD) was found, however, the key metabolites were only slightly elevated in some samples. Biotinidase deficiency was considered but excluded by the finding of normal plasma biotinidase activity. The correct diagnosis was made only at the age of 19 months when severe MCD was found in lymphocytes in the presence of normal plasma biotin concentration. HCS deficiency was confirmed by fibroblast studies. Biotin therapy (20 or 40 mg/day) prevented further episodes and normalized biochemical parameters with so far normal development. During two subsequent pregnancies, 10 mg biotin/day was administered to the mother from the 20th week of gestation. At delivery plasma biotin in cord blood samples was 3 4 times higher than in maternal plasma. The 2nd child was unaffected. In the 3rd pregnancy prenatal diagnosis was performed at 16 weeks of gestation. The concentration of methylcitrate in amniotic fluid was within the normal range and that of 3-hydroxyisovalerate only slightly elevated. However, enzyme assays in cultured amniotic fluid cells were consistent with an affected fetus. At birth, carboxylase activities in lymphocytes of this newborn were only moderately decreased to 37% of mean normal. HCS deficiency was confirmed postnatally in fibroblasts. Development remains normal on biotin therapy (20 mg/day).

CONCLUSION

Prenatal diagnosis in families with milder forms of HCS deficiency has to be performed by enzyme assays in cultured amniotic cells since organic acid analysis of amniotic fluid may be inconclusive in affected fetuses. Biotin administered prenatally is effectively taken up by the fetus and prevents functional deficiency of the carboxylases in an affected newborn.

Authors+Show Affiliations

University Children's Hospital, Basel, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9686819

Citation

Suormala, T, et al. "Late-onset Holocarboxylase Synthetase-deficiency: Pre- and Post-natal Diagnosis and Evaluation of Effectiveness of Antenatal Biotin Therapy." European Journal of Pediatrics, vol. 157, no. 7, 1998, pp. 570-5.
Suormala T, Fowler B, Jakobs C, et al. Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. Eur J Pediatr. 1998;157(7):570-5.
Suormala, T., Fowler, B., Jakobs, C., Duran, M., Lehnert, W., Raab, K., Wick, H., & Baumgartner, E. R. (1998). Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. European Journal of Pediatrics, 157(7), 570-5.
Suormala T, et al. Late-onset Holocarboxylase Synthetase-deficiency: Pre- and Post-natal Diagnosis and Evaluation of Effectiveness of Antenatal Biotin Therapy. Eur J Pediatr. 1998;157(7):570-5. PubMed PMID: 9686819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. AU - Suormala,T, AU - Fowler,B, AU - Jakobs,C, AU - Duran,M, AU - Lehnert,W, AU - Raab,K, AU - Wick,H, AU - Baumgartner,E R, PY - 1998/8/1/pubmed PY - 1998/8/1/medline PY - 1998/8/1/entrez SP - 570 EP - 5 JF - European journal of pediatrics JO - Eur. J. Pediatr. VL - 157 IS - 7 N2 - UNLABELLED: The clinical and biochemical findings in a family with late-onset holocarboxylase synthetase (HCS) deficiency are described. The index patient had two life-threatening episodes of metabolic decompensation at the age of 13 and 18 months with ketotic hypoglycaemia, vomiting and progressive loss of consciousness. The child recovered without biotin therapy. Organic aciduria characteristic of multiple carboxylase deficiency (MCD) was found, however, the key metabolites were only slightly elevated in some samples. Biotinidase deficiency was considered but excluded by the finding of normal plasma biotinidase activity. The correct diagnosis was made only at the age of 19 months when severe MCD was found in lymphocytes in the presence of normal plasma biotin concentration. HCS deficiency was confirmed by fibroblast studies. Biotin therapy (20 or 40 mg/day) prevented further episodes and normalized biochemical parameters with so far normal development. During two subsequent pregnancies, 10 mg biotin/day was administered to the mother from the 20th week of gestation. At delivery plasma biotin in cord blood samples was 3 4 times higher than in maternal plasma. The 2nd child was unaffected. In the 3rd pregnancy prenatal diagnosis was performed at 16 weeks of gestation. The concentration of methylcitrate in amniotic fluid was within the normal range and that of 3-hydroxyisovalerate only slightly elevated. However, enzyme assays in cultured amniotic fluid cells were consistent with an affected fetus. At birth, carboxylase activities in lymphocytes of this newborn were only moderately decreased to 37% of mean normal. HCS deficiency was confirmed postnatally in fibroblasts. Development remains normal on biotin therapy (20 mg/day). CONCLUSION: Prenatal diagnosis in families with milder forms of HCS deficiency has to be performed by enzyme assays in cultured amniotic cells since organic acid analysis of amniotic fluid may be inconclusive in affected fetuses. Biotin administered prenatally is effectively taken up by the fetus and prevents functional deficiency of the carboxylases in an affected newborn. SN - 0340-6199 UR - https://www.unboundmedicine.com/medline/citation/9686819/Late_onset_holocarboxylase_synthetase_deficiency:_pre__and_post_natal_diagnosis_and_evaluation_of_effectiveness_of_antenatal_biotin_therapy_ L2 - https://dx.doi.org/10.1007/s004310050881 DB - PRIME DP - Unbound Medicine ER -