Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey
-
Berna Seker Yilmaz
,
Neslihan Onenli Mungan
Abstract
Background:
Biotinidase deficiency (BD) is an autosomal recessive inborn error of metabolism characterized by neurologic and cutaneous symptoms and can be detected by newborn screening. Newborn screening for BD was implemented in Turkey at the end of 2008.
Methods:
In total, 203 patients who were identified among the infants detected by the newborn screening were later confirmed to have BD through measurement of serum biotinidase activity. We also performed BTD mutation analysis to characterize the genetic profile.
Results:
Twenty-seven mutations were identified. The most commonly found variants were c.1330G>C (p.D444H), c.1595C>T (p.T532M), c.470G>A (p.R157H), and c.198_104delGCGGCTGinsTCC (p.C33Ffs ) with allele frequencies of 0.387, 0.175, 0.165 and 0.049, respectively. Three novel pathogenic and likely pathogenic variants were identified: p.W140* (c.419G>A), p.S319F (c.956C>T) and p.L69Hfs*24 (c.192_193insCATC). We also identified three mutations reported in just one patient in the past (p.V442Sfs*59 [c.1324delG], p.H447R [c.1340A>G] and p.198delV [c.592_594delGTC]). Although all of the patients were asymptomatic under the treatment of biotin, only one patient, who had the novel c.419G>A homozygous mutation became symptomatic during an episode of acute gastroenteritis with a presentation of ketosis and metabolic acidosis. Among the screened patients, 156 had partial and 47 had profound BD.
Conclusions:
We determined the mutation spectra of BD from the southeastern part of Turkey. The results of this study add three more mutations to the total number of mutations described as causing BD.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Wolf B. Biotinidase: its role in biotinidase deficiency and biotin metabolism. J Nutr Biochem 2005;16:441–5.10.1016/j.jnutbio.2005.03.024Search in Google Scholar
2. Thodi G, Schulpis KH, Molou E, Georgiou V, Loukas LK, et al. High incidence of partial biotinidase deficiency cases in newborns of Greek origin. Gene 2013;524:361–2.10.1016/j.gene.2013.04.059Search in Google Scholar
3. Salbert BA, Pellock JM, Wolf B. Characterization of seizures associated with biotinidase deficiency. Neurology 1993;43:1351–4.10.1212/WNL.43.7.1351Search in Google Scholar
4. Wolf B, Heard GS, Weissbecker KA, McVoy JR, Grier RE, et al. Biotinidase deficiency: Initial clinical features and rapid diagnosis. Ann Neurol 1985;18:614–7.10.1002/ana.410180517Search in Google Scholar
5. Ohlsson A, Guthenberg C, Holme E, von Döbeln U. Profound biotinidase deficiency: a rare disease among native Swedes. J Inherit Metab Dis 2010;33:175–80.10.1007/s10545-010-9065-ySearch in Google Scholar
6. McVoy JR, Levy HL, Lawler M. Partial biotinidase deficiency: clinical and biochemical features. J Pediatr 1990;116:78–83.10.1016/S0022-3476(05)81649-XSearch in Google Scholar
7. Möslinger D, Stockler-Ipsiroglu S, Scheibenreiter S. Clinical and neuropsychological outcome in 33 patients with biotinidase deficiency ascertained by nationwide newborn screening and family studies in Austria. Eur J Pediatr 2001;160:277–82.10.1007/s004310100740Search in Google Scholar
8. Heard GS, Wolf B, JeVerson RG, Weissbecker KA, Nance VE, et al. Screening for biotinidase deficiency: results of a 1-year pilot study. J Pediatr 1986;108:40–6.10.1016/S0022-3476(86)80766-1Search in Google Scholar
9. Wolf B. Clinical issues and frequent questions about biotinidase deficiency. Mol Genet Metab 2010;100:6–13.10.1016/j.ymgme.2010.01.003Search in Google Scholar PubMed
10. Knight HC, Reynolds TR, Meyers GA, Pomponio RJ, Buck GA, et al. Structure of the human biotinidase gene. Mamm Genome 1998;9:327–30.10.1007/s003359900760Search in Google Scholar PubMed
11. Pindolia K, Jordan M, Wolf B. Analysis of mutations causing biotinidase deficiency. Hum Mutat 2010;31:983–91.10.1002/humu.21303Search in Google Scholar PubMed
12. Heard GS, SecorMcVoy JR, Wolf BA. A screening method for biotinidase deficiency in newborns. Clin Chem 1984;30:125–7.10.1093/clinchem/30.1.125Search in Google Scholar
13. Kavasoglu AN, Onay H, Kose M, Durmaz A, Kalkan S, et al. A case diagnosed with biotinidase deficiency in newborn screening test. Turkiye Klinikleri J Pediatr 2014;23:49–52.Search in Google Scholar
14. Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Exp Rev Endocrinol Metab 2008;3:715–24.10.1586/17446651.3.6.715Search in Google Scholar PubMed PubMed Central
15. Wolf B. Disorders of biotin metabolism. In: Scriver CR, Baudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 2001:3935–62.Search in Google Scholar
16. Karaca M, Ozgül RK, Unal O, Yucel-Yilmaz D, Kılıc M, et al. Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. Eur J Pediatr 2015;174:1077–84.10.1007/s00431-015-2509-5Search in Google Scholar PubMed
17. Procter M, Wolf B, Mao R. Forty-eight novel mutations causing biotinidase deficiency. Mol Genet Metab 2016;117:369–72.10.1016/j.ymgme.2016.01.002Search in Google Scholar PubMed
18. Neto EC, Schulte J, Rubim R, Lewis E, DeMari J, et al. Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations. Braz J Med Biol Res 2004;37:295–9.10.1590/S0100-879X2004000300001Search in Google Scholar PubMed
19. Pomponio RJ, Coskun T, Demirkol M, Tokatli A, Ozalp I, et al. Novel mutations cause biotinidase deficiency in Turkish children. J Inherit Metab Dis 2000;23:120–8.10.1023/A:1005609614443Search in Google Scholar
20. Katie L, Swango MD, Huner G, Pronicka E, Sykut-Cegielska JJ, et al. Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene. Hum Genet 1998;102:571–5.10.1007/s004390050742Search in Google Scholar PubMed
21. Wolf B. Children with profound biotinidase deficiency should be treated with biotin regardless of their residual enzyme activity. Eur J Pediatr 2002;161:167–8.10.1007/s00431-001-0902-8Search in Google Scholar PubMed
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Articles in the same Issue
- Frontmatter
- Review
- Vitamin D deficiency in childhood: old lessons and current challenges
- Original Articles
- Brain gray matter volume differences in obese youth with type 2 diabetes: a pilot study
- Prevalence and clinical presentation at the onset of type 1 diabetes mellitus among children and adolescents in AL-Baha region, Saudi Arabia
- Whole blood viscosity and cerebral blood flow velocities in obese hypertensive or obese normotensive adolescents
- The utility of body mass index as an indicator for lipid abnormalities in non-fasting children
- Association of insulin-like growth factor-1 and IGF binding protein-3 with 25-hydroxy vitamin D in pre-pubertal and adolescent Indian girls
- The safety of Lipistart, a medium-chain triglyceride based formula, in the dietary treatment of long-chain fatty acid disorders: a phase I study
- Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche
- Age of pubertal events among school girls in Lagos, Nigeria
- Evaluation of basal sex hormone levels for activation of the hypothalamic–pituitary–gonadal axis
- PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and review of the literature
- Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey
- Case Reports
- Emergence of insulin resistance following empirical glibenclamide therapy: a case report of neonatal diabetes with a recessive INS gene mutation
- A rare unbalanced Y:autosome translocation in a Turner syndrome patient
- A Japanese patient with congenital central hypothyroidism caused by a novel IGSF1 mutation
- Growth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin
