Biotinidase deficiency is a multiple carboxylase deficiency, in which the body is unable to use biotin. Biotin is a vitamin and a coenzyme for four carboxylases necessary for normal metabolism in humans, and, thus, plays an important role in the metabolism of fats and amino acids, aerobic respiration, and cell growth. Children with a deficiency of the biotinidase enzyme may present with symptoms of hypotonia, developmental delays and breathing difficulties, as early as in the first few months of life. Profound deficiency may even manifest in the form of seizures. Those with a profound deficiency have less than 10% of normal biotinidase activity left. Partial biotinidase deficiency is characterized by 10-30% of enzyme activity. If not treated, this condition can lead to several complications, including hearing and vision loss, ataxia, and alopecia.
Neonatal screening can easily pick up the presence of biotinidase deficiency in newborns. This screening usually involves taking a tiny amount of blood from a prick in the baby's heel. Early identification of the condition, sometimes even before any symptoms appear, is important, since immediate treatment can prevent many complications. Treatment is very simple, and merely involves the oral administration of 5-10 mg of biotin per day. This treatment, however, is life-long. Treatment, if missed in the neonatal period, can lead to complications, which might need additional management. Hearing and/or vision aids may be required by some affected patients. Developmental delays may also require appropriate interventions. Recent studies have shown conclusively that children identified with the disorder in the neonatal period, and treated even before the emergence of any clinical symptoms showed no neurological complications, in contrast to children treated after the appearance of clinical signs.
In 2003, the Hamad Medical Corporation, in partnership with the University Children's Hospital of Heidelberg built a comprehensive newborn screening program. Between December 2003 and July 2006, Lindner et al, 2007, investigated 25,214 neonates born in Qatar for inborn errors of metabolism and endocrine disorders. Two neonates were diagnosed with biotinidase deficiency. Treatment was started immediately upon receiving the positive results.
Sweetman et al, 1982, described a 3-month-old Saudi boy who presented with degenerative brain disease, convulsive disorder, and seborrhoeic dermatitis. His parents were first cousins; one of their daughters died at 3-4 months of age with convulsions, vomiting, poor feeding, and failure to thrive. Urine analysis demonstrated that 3-hydroxyisovaleric acid, 3-hydroxypropionic acid, lactic acid and methylcitric acid were all abnormally elevated.
Between 1992 and 1996, Joshi et al, 1999, identified 20 cases of biotinidase deficiency in children at the King Faisal Specialist Hospital and Research centre. Patients were treated with 10 mg of biotin twice a day. While recovery from seizures, dermatitis, hypotonia, and poor feeding were reported within a few days of therapy, developmental functions and alopecia improved within weeks. Howver, sensorineural deafness, poor speech and optic atrophy could not be alleviated.
Moammar et al, 2010, reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Organic acidopathies (OA) were diagnosed in 48 out of 248 cases (19%), which constitute the second largest group of IEM found in this cohort after lysosomal storage disease. Among OA, three cases from three families were diagnosed to have biotinidase deficiency. The estimated incidence of biotinidase deficiency in this cohort was 2 in 100,000 live births.
Sarafoglou et al. (2009) reported the results of the Minnesota Newborn Screening Program (MN NBS) for the period between years 2004 and 2008. Of 264,727 infants screened by the Wolf colorimetric system five were identified to have profound biotinidase deficiency (0.1 to <0.6 nmol/min per ml) and 26 with partial BTD (0.9 to 2.3 nmol/min per ml). All these children were from new immigrant groups. Among the five cases of profound BTD four were of Somali ethnic background. All four Somali patients have the p.P497S mutation, with one of the four being homozygous for the mutation. The three compound heterozygotes all have a novel mutation (p.P142T) and two of them have another change (p.Y428Y) that has never been described.