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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 58, Num. 2, 2010, pp. 323-324

Neurology India, Vol. 58, No. 2, March-April, 2010, pp. 323-324

Letter To Editor

Biotin responsive seizures and encephalopathy due to biotinidase deficiency

1 Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman
2 Department of Biochemistry, Sultan Qaboos University Hospital, Muscat, Oman

Correspondence Address: Surendra Nath Joshi, Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman,

Date of Acceptance: 31-Jan-2010

Code Number: ni10084

PMID: 20508364

DOI: 10.4103/0028-3886.63783


Biotinidase deficiency is a disorder of multiple carboxylase deficiency with an autosomal recessive mode of inheritance [1] and was first described by Wolf and colleagues in 1983. [2] The reported incidence in various neonatal screening programs worldwide is 1:60,000 live births. [3] Biotin, a vitamin B complex is necessary to activate the carboxylase enzymes system. The carboxylase enzymes are essential for the metabolism of amino acids, carbohydrate and fatty acids. Biotin is normally required in a very small quantity as most of it is re-cycled by biotinidase enzyme. Biotinidase deficiency results in the depletion of body biotin stores, thus leading to the failure of carboxylase enzymes causing severe metabolic consequences. Biotin deficiency is characterized by acute metabolic encephalopathy, neuro-developmental delay, anti-epileptic drug resistant seizure disorder, muscular hypotonia, alopecia and skin rash. [3] In this report, we present the first confirmed case of Biotinidase deficiency from Oman.

A boy aged three months presented with history of recurrent seizures since 35 days of age. He used to have five to six convulsive seizures a day, each lasting for five minutes. He was extremely lethargic and sleepy most of the time with poor cry, sucking, and motor activity. Three of his siblings had died with similar illness [Figure - 1]. Seizures were uncontrolled with phenobabitone and clonazepam. He was tried on pyridoxine without any effect. On examination, there were no dysmorphic features or neuro-cutaneous markers. The scalp hair was very thin and scanty and the eye brows and eye lashes were virtually absent [Figure - 2]. He also had nappy dermatitis. Neurological examination revealed a lethargic child with dull and expressionless face. There was no eye contact and he could not track the moving objects. There was generalized hypotonia with marked head lag. The neonatal reflexes were very sluggish. The deep tendon reflexes were exaggerated. Rest of the systemic examination was unremarkable. Investigations revealed mildly elevated ammonia 127 micromole/L (normal 16 - 60 micromole/L) and lactate 3.9 micromole/L (normal 0.5 - 2.0 micromole/L). Blood sugar, renal, hepatic and bone profile were normal and no keto-acidosis. EEG revealed burst suppression pattern and asynchrony, multi-focal spike discharges consisting with early infantile encephalopathy [Figure - 3]. Magnetic resonance imaging (MRI) of brain revealed diffuse white matter changes with marked cortical atrophy. Tandem mass spectrometry revealed high C5 hydroxycarnitine levels. The urine organic acid profile showed marked increase of 3-hydroxyisovarelate, 3-methylcrotonylglycine and methyl citrate suggesting the possibility of multiple carboxylase deficiency, most likely biotinidase deficiency. Serum Biotinidase assay was < 0.5 nMol/ml/mt activity of the enzyme (normal range 4.4-12 nMol/ml/mt).The child was started on biotin 10 mg twice a day. Within two days of starting biotin patient was seizure free and was more awake and started to feed better. Serum ammonia as well as lactate levels normalized. He was weaned off antiepileptic medication within a week. Subsequent follow-ups at five months and eight months of age showed dramatic improvement in visual attention and motor activity with a good head control, and normal psychomotor development for age including hair growth [Figure - 4]. EEG was completely normal after 6 weeks of treatment. MRI after two months of treatment revealed improvement.

This case demonstrates the importance of suspecting biotinidase deficiency in any young infant presenting with drug resistance seizures and encephalopathy with the additional clinical features of seborhoeic dermatitis, alopecia with loss of eye lashes and eye brows. In such infants a trial of biotin for a few days is of importance to prevent developmental delay and death. The treatment is life long. Antenatal diagnosis of biotinidase deficiency is now possible and neonatal screening can help in early diagnosis.


1.Sweetman L. Two forms of biotin-responsive multiple carboxylase deficiency. J Inherit Metab Dis 1981;4:53-4.   Back to cited text no. 1  [PUBMED]  
2.Wolf B, Grier RE, Allen RJ, Goodman SI, Kien CL. Biotinidase deficiency: The enzyme defect in late-onset multiple carboxylase deficiency. Clin Chem Acta 1983;131:273-81.  Back to cited text no. 2    
3.Wolf B. Disorders of biotin metabolism: Treatable neurological syndromes. In: Rosenberg R, Prusiner SB, Di Mauro S, Barchi RL, Kunkel LM, editors. The molecular and genetic basis of neurological disease. Stoneham MA: Butterworth; 1993.  Back to cited text no. 3    

Copyright 2010 - Neurology India

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