A two days old newborn with partial biotinidase deficiency presenting with treatment resistant convulsions

Year 2019, Volume: 36 Issue: 4, 125 - 129, 02.03.2020

İşıl Özer , Sema Eser Canan Aygün

Abstract

Biotinidase deficiency (BD) is an autosomal recessive metabolic disorder characterized primarily by cutaneous and neurologic abnormalities (OMIM 253260). Symptoms usually appear by three months of age (minimum 12th day) with seizures as the most frequent initial symptom. We decided to present a patient with partial biotinidase deficiency since she presented with neurological findings as early as the second day of life in order to discuss the additional factors leading to such early signs. The baby was born via normal spontaneous delivery as the second child from nonconsanguineous healthy parents; a 33-year-old mother and 35-year-old father with a birth wieght was 3440 g. Her first clinical symptoms were cyanosis and tonic convulsions after feeding on the second day. Both her parents and her 17-month-old brother were healthy. On physical examination 1/6 pansistolic murmur was heard, diaper dermatites and sacral dimple was observed as well. She was admitted to Neonatal Intensive Care Unit (NICU) for the investigation and treatment of neonatal convulsion. Despite the use of phenobarbital and levetiracetam, apnea and generalized convulsions occurred thrice in the NICU. Biochemical evaluation during these convulsions revealed hypoglycemia (49 mg/dl) and hyperammonemia (150 mcmol/L); albeit her carnitine and aminoacid profile were nonspecific. Her further neurological evaluation by electroencephalography, and cranial magnetic resonance imaging was normal. Seizures were controlled with biotin and folate therapy. Final laboratorial evaluation showed a biotinidase activity of 2.60U/L, (3.5-13.80) and the genetic tests c.1330 G>C (p.Asp444His heterozygous) were related with biotinidase deficiency and A1298 C, C677T compound heterozygous mutations related to Methylene tetra hyrofolate deficiency (MTHFR). Both biotinidase deficiency and MTHFR may cause convulsions. However, the presence of neurologic symptoms as early as the second day of life has not been reported for both before. The coexistence of these diseases, which may cause similar neurological findings, should be investigated as a cause of early clinical findings. Until a satisfactory answer to this question is found, biotin and folate may be considered as a treatment option for early neonatal convulsions and coexistence of the biotinidase deficiency and MTHFR mutations should be investigated. 

Keywords

Neonatal convulsion, Biotinidase deficiency, Metilen Tetra Hydro Folate Deficiency, sacral dimple, diaper dermatidis

References

• Baumgartner, E.R., Suormala, T., Wick, H., Bausch, J., Bonjour, J.P., 1985. Biotinidase deficiency: factors responsible for the increased biotin requirement. JIMD. 8,59-64.
• Baykal, T., Gokcay, G., Gokdemir, Y., Demir, F., Seckin, Y., Demirkol, M., Jensen, K., Wolf, B., 2005. Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases. JIMD. 28,903-12.
• Blom, H.J., Shaw, G.M., den Heijer, M., Finnell, R.H., 2006. Neural tube defects and folate: case far from closed. Nature reviews. 7,724–31.
• Bousounis, D.P., Camfield, P.R., Wolf, B., 1993. Reversal of brain atrophy with biotin treatment in biotinidase deficiency. Neuropediatrics. 24, 214-7.
• Burton, B.K., Roach, E.S., Wolf, B., Weissbecker, K.A., 1987.Sudden death associated with biotinidase deficiency. Pediatrics, 79,482-3.
• Dunkel, G., Scriver, C., Clow, C., Melancon, S., Lemieux, B., Grenier, A., Laberge, C., 1989. Prospective ascertainment of complete and partial serum biotinidase deficiency in the newborn. JIMD. 131–138.
• Frosst, P., Zhang, Z.X., Pai, A., Rozen. R., 1996.The methylenetetrahydrofolate reductase (MTHR) gene maps to distal mouse chromosome 4. Mammalian Genome. 7,864-869.
• Guttormsen, A.B., Ueland, P.M., Nesthus, I., Nygard, O., Schneede, J., Vollset, S.E., Refsum, H. 1996. Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (equal to or greater than 40 micromole/liter): the Hordaland homocysteine study. J. Clin. Invest.98, 2174-2183.
• Heard, G.S., Wolf, B., Jefferson, L.G., Weissbecker, K.A., Nance, W.E., Napolitano, A., Mitchell, P.L., Lambert, F.W., Linyear, A.S., 1986. Neonatal screening for biotinidase deficiency: results of a 1-year pilot study. J. Pediatr. 108,40-46.
• Heller, A.J., Stanley, C., Shaia, W.T., Sismanis, A., 2002. Spencer RF; Wolf BLocalization of biotinidase in the brain: implications for its role in hearing loss in biotinidase deficiency. Hear Res. 173,62-8.
• Hoffman, T.L., Simon, E.M., Ficicioglu, C., 2005. Biotinidase deficiency: the importance of adequate follow-up for an inconclusive newborn screening result Eur J Ped.164,298-301.
• Holm, P.I., Hustad, S., Ueland, P.M., Vollset, S.E., Grotmol, T., Schneede, J., 2007. Modulation of the homocysteine-betaine relationship by methylenetetrahydrofolate reductase 677C-T geneotypes and B-vitamin status in a large-scale epidemiological study. J. Clin. Endocr. Metab.92,1535-1541.
• Jacques, P.F., Bostom, A.G., Williams, R.R., Ellison, R.C., Eckfeldt, J.H., Rosenberg, I.H., Selhub, J., Rozen, R., 1996. Relation between folate status, a common mutation in methylenetetra hydrofolate reductase, and plasma homocysteine concentrations. Circulation. 93,7-9.
• Kalkanoğlu- Sivri, H.S, Aydan-Genç, G., Tokatlı, A., Dursun, A., Coşkun, T., Aydın, H.İ., Sennaroğlu, L., et al., 2007. Hearing loss in biotinidase deficiency: Genotype – phenotype correlation. J Pediatr.150,439-442.
• Motulsky, A., 1996. Nutritional ecogenetics: homocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acid. Am J Hum Genet. 58,17–20.
• OMIM 253260 (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=253260)
• Özer, I., Özçetin, M., Karaer, H., Kurt, S.G., Şahin, Ş,. 2011. Retrospective Approach to Methylenetetrahydrofolate Reductase Mutations in Children. Ped Neuro.45,34-38.
• Rosenblatt, D.S., Fowler, B., 2016. Disorders of Cobalamin and Folate Transport and Metabolism In: Jean-Marie Saudubray,Matthias R. Baumgartner,John Walter (eds). Inborn Metabolic Diseases, Springer Berlin, Heidelberg. 385-399.
• Swango, K.L., Demirkol, M., Huner, G., Pronicka, E., Sykut-Cegielska, J., Schulze, A., Mayatepek, E,, Wolf, B., 1998. Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene. Hum Genet. 102,571-5.
• Sweetman, L., Nyhan, W.L., 1986. Inheritable Biotin-Treatable Disorders and Associated Phenomena Annu Rev Nutr.6, 317-43.
• Weisberg, I., Tran, P., Christensen, B., Sibani, S., Rozen, R., 1998. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Gen Metab. 64,169–72.
• Wolf, B., 2001. Disorders of biotin metabolism. In: Scriver, C., Beaudet, A., Sly, W., Valle, D. (eds) The metabolic and molecular Basies of inherited disease. McGraw-Hill, New York, 3935.
• Wolf, B., Heard, G.S., Weissbecker, K.A., McVoy, J.R., Grier, R.E., Leshner, R.T., 1985 Biotinidase deficiency: initial clinical features and rapid diagnosis. Ann Neurol. 18,614-7.
• Wolf, B., 1991.Worldwide survey of neonatal screening for biotinidase deficiency. JIMD.14,928-31.