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

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.