It usually presents with ataxia and seizures, though atypical presentations have also been described. [ncbi.nlm.nih.gov]

• Turkish

  Here, a case is presented with two rare genetic disorders, biotinidase deficiency and juvenile myelomonocytic leukemia, in a Turkish infant. [ncbi.nlm.nih.gov]

  Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. Eur. J. Pediatr. 2015; :None. PMID: 25754625 Milánkovics, I, et al. [invitae.com]

  Wolf, Novel mutations cause biotinidase deficiency in Turkish children, Journal of Inherited Metabolic Disease, 23, 2, (120-128), (2000). [doi.org]

• Fulminant Sepsis

  Emergency department presentation of biotinidase deficiency: fulminant sepsis in a 4-year-old Hispanic male. Pediatr Emerg Care. 2004 Jan. 20(1):37-9. [Medline]. Riudor E, Vilaseca MA, Briones P, et al. [emedicine.com]

• Sighing

  We describe a 7-year old boy with subacute progressive quadriplegia and "sighing" respirations. Severe biotinidase deficiency was established, and the patient demonstrated complete recovery with biotin supplementation. [ncbi.nlm.nih.gov]

• Neonatal Jaundice

  RESULTS: Most individuals were identified by neonatal screening (n = 66/72). When consecutive results for the same patient were compared, age, prematurity and neonatal jaundice appeared to affect the level of biotinidase activity. [ncbi.nlm.nih.gov]

  Furthermore, jaundiced neonates may have reduced biotinidase activity [ 9 ]. [bmcmedgenet.biomedcentral.com]

• Hearing Impairment

  Some symptomatic children showed residual impairments: hearing impairment (n=2), optic atrophy (n=2), both hearing impairment and optic atrophy (n=2). In addition, symptomatic children had a higher risk of delayed motor and speech development. [ncbi.nlm.nih.gov]

  All 11 symptomatic children had residual enzyme activity of n =2), optic atrophy ( n =2), both hearing impairment and optic atrophy ( n =2). In addition, symptomatic children had a higher risk of delayed motor and speech development. [doi.org]

• Alopecia

  There was diffuse alopecia, seborrheic dermatitis and perioral desquamating lesions [Figure 1]. Bilateral Babinski was positive, jerks were brisk (grade 3) in all four limbs. [e-ijd.org]

  Biotinidase deficiency may be seen early in the neonatal period without the characteristic findings such as alopecia and seborrheic dermatitis. This diagnosis should be considered in patients with infantile spasms. [ncbi.nlm.nih.gov]

• Eczema

  In addition, sparse scalp hair and chronic intractable eczema has been described in this syndrome. We report a 26-month-old girl with the disease and partial biotinidase deficiency. [ncbi.nlm.nih.gov]

  Individuals with untreated biotinidase deficiency may develop problems such as hypotonia (low muscle tone), eczema (skin rash), alopecia (hair loss), seizures, developmental delay, breathing problems, ataxia (balance, coordination and movement problem [thinkgenetic.com]

  Some other common features of BTD include eye infections, like pink eye (conjunctivitis), hair loss (alopecia), and a certain type of skin rash called eczema. [rarediseases.org]

  Rashes may be mistaken for eczema, seborrheic dermatitis, or the dermatoses observed in zinc deficiency. [emedicine.medscape.com]

• Sparse Hair

  Sparse hair was seen in four patients, while three did not have any cutaneous manifestation. None of the patients had acidosis or hyperammonemia. The clinical response to biotin was dramatic with seizure control in all patients. [ncbi.nlm.nih.gov]

  Total alopecia was seen in one of the patients and sparse hair was seen in three of our patients. Seborrheic dermatitis was seen in one patient who had sparse hair as well. Three did not have any cutaneous manifestation. [neurologyindia.com]

• Suggestibility

  These findings suggest that biotinidase and possibly biotin plays an important role in hearing. [ncbi.nlm.nih.gov]

• Quadriplegia

  We describe a 7-year old boy with subacute progressive quadriplegia and "sighing" respirations. Severe biotinidase deficiency was established, and the patient demonstrated complete recovery with biotin supplementation. [ncbi.nlm.nih.gov]

In present case, a negative sepsis workup, paucity of clinico-radiological signs despite marked breathlessness, skin changes, severe metabolic acidosis and ketonuria led us to suspect biotinidase deficiency, which was confirmed on enzyme analysis. [indianpediatrics.net]

• Base Deficit

  However, the arterial blood gas analysis revealed a picture of compensated metabolic acidosis with a pH of 7.482, PCO 2 = 15 mmHg, HCO 3 = 11.2 mmol/L and base deficit of - 12 mmol/L [Figure 2]. Serum lactate level was high. [e-ijd.org]

With biotin treatment, these values rose to normal limits for both control groups. [ncbi.nlm.nih.gov]

The seizures are difficult to differentiate from other causes of epileptic encephalopathy, which generally have a poor prognosis. [ncbi.nlm.nih.gov]

Prognosis The prognosis for individuals diagnosed with BTD deficiency is very good, provided they are treated before symptoms occur and are compliant with biotin therapy. [orpha.net]

[…] sub-cortical cyst formation T2: the same changes as above signal abnormalities of the spinal cord may also be seen DWI: areas of restricted diffusion within the signal abnormalities MR spectroscopy: sometimes elevated lactate reduced NAA Treatment and prognosis [radiopaedia.org]

Ohtahara syndrome is a rare epileptic encephalopathy in infants; the underlying etiology is generally thought to be structural brain malformations. [ncbi.nlm.nih.gov]

Etiology BTD deficiency is caused by mutations in the BTD gene (3p25) resulting in reduced or absent BTD activity. This enzyme recycles free, non-protein bound, biotin which is required for multiple biotin-dependent metabolic processes. [orpha.net]

Etiology Mutations in the genes for holocarboxylase synthetase and biotinidase produce deficient or defective enzymes inhibiting the activation of the four carboxylases and limiting the recovery of protein bound biotin for reactivation of the carboxylases [clinicaladvisor.com]

Summary Epidemiology Prevalence of clinical biotinidase (BTD) deficiency is estimated to be 1/61,000. Carrier frequency in the general population is approximately 1/120. [orpha.net]

It does seem that biotin deficiency is usually caused by things that lead to biotinidase deficiency, so let’s look at the data on frequency ( Epidemiology) Biotin Deficiency – Epidemiology Based on the results of worldwide screening of biotinidase deficiency [epiphanyasd.blogspot.com]

Epidemiology Incidence is less than 1 in 60,000 babies - no more than 12 cases per year. [ 3 ] The carrier frequency in the general population is 1 in 120. [ 4 ] Presentation [ 1, 2 ] Usually presents aged 1 week to 2 years (earlier-onset carboxylase [patient.info]

Molecular and Systemic Pathophysiology Biotin is a water-soluble vitamin that as a coenzyme is covalently attached to four carboxylases in humans (Fig. 1 ) [ 1 ]. References 1. Wolf B (2001) Disorders of biotin metabolism. [link.springer.com]

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Biotinidase deficiency is an inherited metabolic disease caused by reduced levels of biotinidase, an enzyme that recycles biotin [mayomedicallaboratories.com]

[…] the neurologic findings remained for a longer period of time. 11 There are even reports of adults with profound biotinidase deficiency who have never had symptoms but were diagnosed because their children had positive results of newborn screening. 2 Pathophysiology [wvdhhr.org]

Newborn screening for biotinidase deficiency (BD) provides prevention of neurological sequelae in patients with low residual enzyme activity by early treatment with oral biotin substitution. [ncbi.nlm.nih.gov]