Biotin Deficiency Clinical Presentation

Updated: Oct 22, 2018
  • Author: Gratias Tom Mundakel, MBBS, DCH; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
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Presentation

History

Presentation depends on the etiology and severity of the deficiency. 

Biotinidase deficiency is the most common etiology; in most developed countries including the US, newborn screening includes tests for biotinidase deficiency and the condition, therefore, is identified in a majority of individuals even before symptoms develop. 

Impaired growth, skin, and hair changes and neurological problems are common in individuals with profound biotinidase deficiency (< 10% normal serum biotinidase activity) who are diagnosed late or are untreated. Individuals with partial biotinidase deficiency (10-30% of normal serum biotinidase activity) usually become symptomatic only during periods of stress, such as an infection. 

Most individuals with untreated profound biotinidase deficiency develop symptoms in early infancy (mean age 3.5 months); however some may develop it as early as one week of life, and others may remain asymptomatic until adolescence. Some individuals present with a single finding and others present with multiple findings.  

The first symptoms are usually associated with the skin and hair [29]  and may include:

  • Dry skin

  • conjunctivitis

  • Seborrheic dermatitis

  • Fungal infections, especially candidiasis. 

  • scaly, red rash, around eyes, nose, mouth, and perineum 

  • Fine and brittle hair

  • brittle nails

  • Hair loss or total alopecia

If undiagnosed and left untreated neurologic symptoms begin to develop. [13, 30, 31, 32, 33, 34, 35, 36]  The most common neurologic findings include the following:

  • hypotonia, motor, weakness, and lethargy 

  • ataxia and developmental delay 

  • Mild depression, which may progress to profound lassitude and, eventually, to somnolence and coma

  • Changes in mental status

  • Generalized muscular pains (myalgias)

  • hallucinations

  • Hyperesthesias and paresthesias

  • seizures (commonly myoclonic, grand mal and focal seizures as well as infantile spasms)

  • progressive spastic paresis and myelopathy

  • Optic atrophy

  • Sensorineural hearing loss may develop in 75% of untreated infants with profound biotinidase deficiency. [24]  

Intestinal tract symptoms also develop and most commonly include the following:

  • Nausea, occasionally severe

  • Vomiting

  • Anorexia

Respiratory symptoms include stridor, apnea and hyperventilation. 

Metabolic problems include organic aciduria, ketolactic acidosis, and mild hyperammonemia. [37]   In severe cases, especially with profound untreated biotinidase deficiency, coma and death may ensue. 

Holocarboxylase synthetase deficiency may present as early as during fetal life with intrauterine growth retardation and abnormal CNS findings. [38]

 

 

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Physical

Physical manifestations usually involve the skin and hair, central and peripheral nervous systems, and intestinal tract.

Skin and hair

The first signs that develop in biotin deficiency are associated with the skin and hair. Dry skin is a consistent finding and is often associated with seborrheic dermatitis, which can be severe. The skin lesions provide an ideal environment for fungal infections that may be resistant to treatment until the biotin-deficient state is reversed. An erythematous periorofacial macular rash is a common finding and may be confused with the rash seen with zinc deficiency. The hair quickly becomes fine and brittle, and total alopecia often develops. [29]

Hearing

Individuals with untreated biotinidase deficiency develop sensorineural hearing loss. [31]   [24]  The hearing loss varies in severity from mild to profound.

Central and peripheral nervous systems

The neurologic signs are multiple [30, 31]  and nonspecific. With untreated, profound biotinidase deficiency seizures [34]  and hypotonia are common. [24] Progressive spastic paresis, myelopathy, encephalopathy, ataxia, and developmental delay may also occur. Occasionally, changes in mental status are observed. They include mild depression, which may progress to profound lassitude, and, eventually, somnolence. Generalized muscular pains (myalgias), hyperesthesias, and paresthesias are common findings that occasionally become disabling. Profound biotinidase deficiency in a 3-year-old boy with progressive spastic paraparesis and ascending weakness but not the typical neurological symptoms was noted by Chedrawi et al. [32] Biotinidase deficiency with hypertonia was noted by Rathi and Rathi. [33]

Intestinal tract

Nausea, occasionally severe, is an occasional finding, as is anorexia. These problems are rarely severe enough to significantly interfere with the adequate oral intake of food.

 

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Causes

Causes of biotin deficiency are discussed under Overview/Pathophysiology

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Physical Examination

Once biotin deficiency has been confirmed, physical exam should be focused on evaluating the extent and severity of the disease and should include a detailed neurological exam, developmental assessment (if appropriate), visual and hearing assessment.  

 

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Complications

Irreversible complications that may develop if treatment is delayed or inadequate include vision problems, sensory-neural hearing loss, ataxia, cognitive impairment, and developmental delay.  [39, 40, 41, 27]

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