eMedicine Specialties > Pediatrics: General Medicine > Nutrition
Biotin Deficiency: Differential Diagnoses & Workup
Updated: Jun 19, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Atypical dermatitides
Seborrheic dermatitis
Fungal infections of the skin
Clinical depression
Generalized muscular disorders
Workup
Laboratory Studies
- According to Neto et al, children with profound biotinidase deficiency have serum enzyme activity of less than 10% of mean normal activity.3 Children with biotinidase deficiency commonly become symptomatic if caregivers do not administer biotin. Children who have partial biotinidase deficiency have 10-30% of mean normal serum biotinidase activity and can develop clinical manifestations of biotinidase deficiency when stressed by an infection or other systemic shocks.
- Urine organic acid levels may be evaluated. Adults who consume raw egg whites for as few as 14-21 days excrete large amounts of b -hydroxyisovalerate in the urine.
- Biotin levels may be assayed. In adults who consume raw egg whites for as few as 14-21 days, biotin levels in the urine and blood are considerably lower than healthy individuals.
- The following tests are rarely needed because the diagnosis of biotin deficiency is primarily based on clinical findings. However, in cases with confusing findings, laboratory studies of the following may be useful:
- Serum ammonia levels
- Urine ketones levels
- Quantitative plasma amino acid levels
- Plasma carnitine levels, both free and total (sometimes termed free and esterified)
- Routine serum chemistry panel
- Moslinger et al assessed the effects of biotinidase deficiency and noted that a sensitive high-power liquid chromatography (HPLC) assay enabled discrimination of 5 patients with residual biotinidase activity (<1%).9 Two patients with 0 activities were homozygous for the G98:d7i3 mutation, and 3 patients (<1%) with activities carried mutations G98:d7i3, R157H, and Q456H. The mutation spectrum of the remaining patients included T532M, A171T+D444H, V62M, C432W, and D444H.
- In a Hungarian series of 58 patients, Laszlo et al noted 17 different mutations, consisting, in part, of 7 novel mutations.4 Six of these new mutations were missense (245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A), and one was a unique allelic double mutation (212T>C; 236G>A).
- Schulpis et al noted that the effects of neonatal jaundice on biotinidase activity are negative.10 Low biotinidase activity can be expressed in full-term babies, premature babies, and small-for-date babies with jaundice. The low activity of the enzyme may be secondary to their impaired liver function. The high total bilirubin levels in the studied groups may inhibit the biotinidase enzyme. Gestational age, as well as total bilirubin levels, bear recording on Guthrie cards for correct evaluation of biotinidase activity.
- In 2003, Dobrowolski et al noted that, in the United States, the 4 mutations most commonly associated with complete biotinidase deficiency are c98:d7i3, Q456H, R538C, and the double mutation D444H:A171T.11 Partial biotinidase deficiency is almost universally attributed to the D444H mutation.
Imaging Studies
- Spastic paraparesis was reported in patients with biotinidase deficiency, and symptoms began in later childhood and early adolescence. A 3-year-old male with biotinidase deficiency presented with skin eruption, ataxia, paraparesis, and MRI findings of myelopathy; all of which resolved with treatment.
Other Tests
- Other tests are rarely indicated.
- In cases with confusing findings, skin biopsy may be performed; however, the results are likely to be nonspecific and of little assistance.
Procedures
- No additional procedures are indicated.
Histologic Findings
- Little is known about possible histologic findings in biotin deficiency, probably because the diagnosis can be readily made based on careful history and physical examination findings. Therefore, histologic specimens are not needed.
More on Biotin Deficiency |
| Overview: Biotin Deficiency |
 Differential Diagnoses & Workup: Biotin Deficiency |
| Treatment & Medication: Biotin Deficiency |
| Follow-up: Biotin Deficiency |
| Multimedia: Biotin Deficiency |
| References |
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References
Boas MA. The Effect of Desiccation upon the Nutritive Properties of Egg-white. Biochem J. 1927;21(3):712-724.1. [Medline].
Adhisivam B, Mahto D, Mahadevan S. Biotin responsive limb weakness. Indian Pediatr. 2007 Mar;44(3):228-30. [Medline].
Neto EC, Schulte J, Rubim R, et al. Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations. Braz J Med Biol Res. Mar 2004;37(3):295-9. [Medline].
Laszlo A, Schuler EA, Sallay E, et al. Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies. J Inherit Metab Dis. 2003;26(7):693-8. [Medline].
Yetgin S, Aytac S, Kalkanoglu S, Coskun T, Ortmann C, Kratz C, et al. Biotinidase deficiency and juvenile myelomonocytic leukemia in a Turkish infant of consanguineous parents. Pediatr Hematol Oncol. 2007 Sep;24(6):453-5. [Medline].
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Moslinger D, Muhl A, Suormala T, Baumgartner R, Stockler-Ipsiroglu S. Molecular characterisation and neuropsychological outcome of 21 patients with profound biotinidase deficiency detected by newborn screening and family studies. Eur J Pediatr. Dec 2003;162 Suppl 1:S46-9. [Medline].
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Dobrowolski SF, Angeletti J, Banas RA, Naylor EW. Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency. Mol Genet Metab. Feb 2003;78(2):100-7. [Medline].
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Mock NI, Malik MI, Stumbo PJ, Bishop WP, Mock DM. Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency. Am J Clin Nutr. Apr 1997;65(4):951-8. [Medline].
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Welling DB. Long-term follow-up of hearing loss in biotinidase deficiency. J Child Neurol. 2007 Aug;22(8):1055. [Medline].
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Further Reading
Keywords
biotin deficiency, carboxylase, carboxylase deficiency, egg-white injury, egg-white syndrome, egg-white injury syndrome, biotinidase deficiency, inherited biotinidase deficiency, nutritional disorder, severe dermatitis, loss of hair, lack of muscular coordination, avidin, propionyl coenzyme A carboxylase, propionyl CoA carboxylase, PCC, pyruvate carboxylase, PC, β-methylcrotonyl CoA carboxylase, β-MCC, acetyl coenzyme A carboxylase, acetyl CoA carboxylase, ACC, acidosis, hypoglycemia, hyperammonemia, coma, seborrheic dermatitis, fungal infections, erythematous periorofacial macular rash
alopecia, mild depression, somnolence, myalgias, hyperesthesias, paresthesias, profound lassitude, prolonged total parenteral nutrition therapy, TPN therapy, phenytoin, primidone, carbamazepine, prolonged oral antibiotic therapy, biotin deficiency, anticonvulsant use, broad-spectrum antibiotic use, acidosis, hypoglycemia, hyperammonemia
