• Users Online: 70
  • Print this page
  • Email this page


 
 
Table of Contents
CASE REPORT
Year : 2021  |  Volume : 15  |  Issue : 3  |  Page : 74-76

An unusual case of biotinidase deficiency with fingertip desquamation


1 Department of Pediatric Metabolic Diseases, Ankara Dr. Sami Ulus Children’s Hospital, Ankara, Turkey
2 Department of Pediatric Metabolic Diseases, Van Bölge Training and Research Hospital, Van, Turkey
3 Department of Pediatric Metabolic Diseases, Hacettepe University, Ankara, Turkey
4 Department of Pediatric Metabolic Diseases, Ankara Yıldırım Beyazıt University, MD, Ankara, Turkey

Date of Submission04-May-2021
Date of Decision08-Jun-2021
Date of Acceptance09-Jun-2021
Date of Web Publication29-Sep-2021

Correspondence Address:
Dr. Asburçe Olgac
Division of Metabolism, Pediatric Metabolic Unit, Dr. Sami Ulus Children’s Hospital, Ankara.
Turkey
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjd.tjd_34_21

Rights and Permissions
  Abstract 

Biotinidase deficiency (BD) is an autosomal recessively inherited inborn error of metabolism that causes multisystemic manifestations, including developmental delay, seizures, hypotonia, vision problems, hearing loss, ketolactic acidosis, and various cutaneous findings at the early stages of life. Treatment consists of oral biotin that is effective in the prevention of complications. We present a case of a 4-year-old boy with partial BD with fingertip desquamation that could be resolved by increasing biotin dosage.

Keywords: Biotin, biotinidase deficiency, desquamation


How to cite this article:
Olgac A, Kilavuz S, Kılıç M, Özgül RK, Kasapkara &S. An unusual case of biotinidase deficiency with fingertip desquamation. Turk J Dermatol 2021;15:74-6

How to cite this URL:
Olgac A, Kilavuz S, Kılıç M, Özgül RK, Kasapkara &S. An unusual case of biotinidase deficiency with fingertip desquamation. Turk J Dermatol [serial online] 2021 [cited 2021 Nov 29];15:74-6. Available from: https://www.tjdonline.org/text.asp?2021/15/3/74/326944




  Introduction Top


Biotin is a water-soluble vitamin that is the coenzyme of several enzymes that play an essential role in carboxylation reactions. Biotinidase is responsible for the cleavage of biotin from biocytin and dietary sources. Biotinidase deficiency (BD) is an autosomal recessively inherited inborn error of metabolism (IEM) that causes multisystemic manifestations, including cutaneous findings.[1],[2]

We present a case of a 4-year-old boy with partial BD deficiency with fingertip desquamation that could be resolved by high-dose oral biotin.


  Case report Top


A 4-year-old boy with known partial BD (biotinidase level: 1, normal level >4.2 nmol/ml/s) was admitted due to fingertip desquamation [Figure 1]. He was the first child of consanguineous parents (first-degree cousins). BD was diagnosed in the neonatal period by neonatal birth screening (NBS), and oral biotin 10 mg/day was initiated. He had no history of fever or infection, hair loss, or seizures. He denied contact with any chemicals or irritants. Desquamation was only limited to the fingertips of hand, not involving the palms and soles. Initial diagnosis of the desquamation was attributed to eczema, and discontinuation using liquid soap was suggested. Moreover, topical steroid was administered for 10 days. He was referred to the metabolism department for further evaluation, since the desquamation persisted despite treatment. Upon admission, he was in good condition. His height and weight were within normal centiles. He did not have any other cutaneous finding apart from desquamation of fingertips. Laboratory analyses revealed normal complete blood count, antistreptolysin O antibody titer, ferritin, plasma zinc level, and vitamins A and E. Incompliance to biotin treatment was denied by parents.
Figure 1: Fingertip desquamation of the presented case

Click here to view


Genetic analysis of BTD gene performed in our center revealed a compound heterozygous mutation (c.98–104del7ins3 and c.1330G>C, p.D444H).

Since the finger desquamation persisted, biotin dosage was increased to 20 mg/day. Interestingly, the desquamations reappeared when the patient could not get biotin for a couple of days since he was out of supply, also involving the palms [Figure 2], and again resolved after restarting of therapy.
Figure 2: Finger desquamation during noncompliance to treatment

Click here to view



  Discussion Top


BD is an autosomal recessively inherited disorder with variable symptoms, especially with neurological and dermatological involvement.[1] Biotin is a cofactor of many carboxylases including pyruvate carboxylase, propionyl-CoA carboxylase (PCC), 3-methylcrotonyl-CoA carboxylase, and acetyl-CoA carboxylase. Due to the deficient activity of these enzymes, the processing of proteins, fats, and carbohydrates is altered in BD that affects the energy metabolism and leads to multisystemic symptoms.[2]

The incidence is suggested to be 1 in 60,000 and may be higher in countries where consanguineous marriages are prevalent, as in Turkey.[2] In many countries, patients are diagnosed at the newborn period by NBS.[3]

The responsible gene for the disease is BTD that is located on chromosome 3p25. Three hundred and sixty-four different variants have been reported up-to-date. Genotype–phenotype correlation is difficult due to the variability of symptoms.[4]

BD is categorized as profound or partial, according to the residual enzyme activity (<10% in profound deficiency, between 10% and 30% in partial deficiency). Although patients with profound BD usually have a mild clinic, severe symptoms have been reported if untreated.[5] Profound BTD deficiency occurs due to the homozygous or compound heterozygous mutations.[4] The underlying mutations are the determinants of the enzyme activity and thus the severity of symptoms.[2] Canda et al.[6] have reported the largest cohort of BD from Turkey in 2012, where p.D444H, p.R157H, and c.98_104delinsTCC were the most commonly detected variants. Our patient is found to be compound heterozygous for the two most commonly reported mutations in Turkey.

Cutaneous signs related to BD include rash, eczema, alopecia, scaly erythematous plaques over the flexors and perioral areas, and seborrheic dermatitis-like eruptions.[7] Lichenification, crusting, and secondary Candida infections may be seen in severe cases. Thin hair, total or partial alopecia have also been reported.[8] The skin changes of BD are suggested to be related to abnormalities in lipid metabolism, since the accumulating propionyl-CoA metabolites due to PCC deficiency may cause an increase in odd-chain fatty acids. Supplementation of biotinidase-deficient mice with omega-6-polyunsaturated fatty acid has been shown to prevent dermatological manifestations of BD.[2]

Diagnosis is usually made by the determination of biotinidase activity in plasma or serum by colorimetric assay method.[2] The exact diagnosis is made by the molecular genetic analysis of BTD.[1],[2],[3]

Standard treatment of profound BD is 10–20 mg/day oral biotin therapy that is usually sufficient for the prevention of irreversible neurological symptoms including optic atrophy, hearing loss, or cognitive disability.[5] Treatment may improve or resolve mild symptoms that may reoccur due to noncompliance with biotin treatment.

Many metabolic disorders present with cutaneous findings.[9] Well-known IEMs that lead to skin findings are summarized in [Table 1]. Periorificial desquamation involving moist areas is most commonly defined in IEMs involving pathways related to biotin metabolism.[7] Any relationship between fingertip desquamation and BD has not previously been reported in the literature, and reports of atypical cases are limited. For example, Navarro et al. have reported an infant with erythematous scaling in the lumbosacral region.
Table 1: Inborn errors of metabolism that cause skin eruptions

Click here to view


Fingertip desquamation is a frequently encountered condition in childhood that is usually benign. Various diseases may cause desquamation of fingertips including eczema, exfoliative keratolysis, allergic contact dermatitis, and psoriasis. Periungual desquamation is also a hallmark of Kawasaki disease. Congenital syphilis and bacterial toxin-mediated disorders are also known to cause desquamation of hands and feet.[10]

In the presented case, although scaling of the fingertips may not be directly related to BD, the refractive nature of the lesions may be due to the disease since topical treatment did not have any effect. Furthermore, they may be an atypical presentation of BD. Nevertheless, increasing the dosage of biotin has resolved the lesions.


  Conclusion Top


Cutaneous findings of a patient with known metabolic disorder may suggest inadequate treatment or poor metabolic control.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wolf B. Clinical issues and frequent questions about biotinidase deficiency. Mol Genet Metab 2010;100:6-13.  Back to cited text no. 1
    
2.
Canda E, Kalkan Uçar S, Çoker M. Biotinidase deficiency: Prevalence, impact and management strategies. Pediatric Health Med Ther 2020;11:127-33.  Back to cited text no. 2
    
3.
Wolf B. Biotinidase deficiency: If you have to have an inherited metabolic disease, this is the one to have. Genet Med 2012;14: 565-75.  Back to cited text no. 3
    
4.
Hymes J, Stanley CM, Wolf B. Mutations in BTD causing biotinidase deficiency. Hum Mutat 2001;18:375-81.  Back to cited text no. 4
    
5.
Wolf B. Why screen newborns for profound and partial biotinidase deficiency? Mol Genet Metab 2015;114:382-7.  Back to cited text no. 5
    
6.
Canda E, Yazici H, Er E, Kose M, Basol G, Onay H, et al. Single center experience of biotinidase deficiency: 259 patients and six novel mutations. J Pediatr Endocrinol Metab 2018;31: 917-26.  Back to cited text no. 6
    
7.
Mock DM. Skin manifestations of biotin deficiency. Semin Dermatol 1991;10:296-302.  Back to cited text no. 7
    
8.
Navarro PC, Guerra A, Alvarez JG, Ortiz FJ. Cutaneous and neurologic manifestations of biotinidase deficiency. Int J Dermatol 2000;39:363-5.  Back to cited text no. 8
    
9.
García-Cazorla A, Wolf NI, Mochel F, Hoffmann GF. Neurological disease. In: Hoffman GF, Zschocke J, Nyhan WL, editors. Inherited Metabolic Diseases: A Clinical Approach. Berlin Heidelberg: Springer; 2017. p. 251-92.  Back to cited text no. 9
    
10.
Mancini AJ, Krowchuk DP.Pediatric Dermatology: A Quick Diagnosis Deck. 2nd ed. Itaska, IL: American Academy of Pediatrics; 2020.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Case report
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed409    
    Printed8    
    Emailed0    
    PDF Downloaded55    
    Comments [Add]    

Recommend this journal