Dermatologic Signs of Biotin Deficiency Leading to the Diagnosis of Multiple Carboxylase Deficiency

Abstract:  The biotin‐responsive, multiple carboxylase deficiencies are autosomal recessively inherited disorders of metabolism in which biotin‐dependent carboxylases show diminished activity. This results in an accumulation of organic acids in the urine. The clinical picture involves the nervous system, skin, respiratory system, digestive system, and immune system. The disorder has a good prognosis if biotin therapy is introduced early. If not, it can result in irreversible damage to the central nervous system and early death from metabolic acidosis. We report a 4‐year‐old girl with unexplained seizures that did not respond well to anticonvulsants. The development of skin problems, which histologically could match the diagnosis of a nutritional dermatitis, together with the fact that the child was constantly eating without gaining weight, led us to the diagnosis of a metabolic disorder. The accumulation of organic acids in the urine suggested the possibility of a biotin deficiency. With biotin therapy the skin problems resolved completely. The seizures also diminished. This case shows that in young children with unexplained seizures that do not respond well to classic anticonvulsant therapy, the possibility of biotin deficiency should always be considered. This article also includes a thorough review of the skin manifestations and other problems caused by biotin deficiency.

[1]  T. Suormala,et al.  Biotinidase deficiency: Clinical course and biochemical findings , 1984, Journal of Inherited Metabolic Disease.

[2]  S. Packman,et al.  Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: Contribution to the prenatal diagnosis of inherited disorders of leucine catabolism , 1984, Journal of Inherited Metabolic Disease.

[3]  L. Sweetman.  Two forms of biotin-responsive multiple carboxylase deficiency , 1981, Journal of Inherited Metabolic Disease.

[4]  J. Leonard,et al.  Studies on cultured fibroblasts from patients with defects of biotin-dependent carboxylation , 1981, Journal of Inherited Metabolic Disease.

[5]  D. Mock.  Biotin status: which are valid indicators and how do we know? , 1999, The Journal of nutrition.

[6]  T. Suormala,et al.  Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy , 1998, European Journal of Pediatrics.

[7]  K. Raymond,et al.  [Prevalence study of biotinidase deficiency in newborns]. , 1998, Revista de saude publica.

[8]  Isac Bruck,et al.  Estudo de prevalência em recém-nascidos por deficiência de biotinidase , 1998 .

[9]  R. Nelson,et al.  Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. , 1998, Journal of pediatric gastroenterology and nutrition.

[10]  E. Ortega,et al.  Biotin deficiency induces changes in subpopulations of spleen lymphocytes in mice. , 1998, The American journal of clinical nutrition.

[11]  A. Haagerup,et al.  [Multiple carboxylase deficiency]. , 1998, Ugeskrift for laeger.

[12]  M. F. Christensen,et al.  Biotinidase deficiency: two cases of very early presentation , 1997 .

[13]  M. Dyken,et al.  Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants , 1997, Neurology.

[14]  T. Suormala,et al.  Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. , 1997, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[15]  S. Skaper,et al.  Biotin deficiency facilitates kindling hyperexcitability in rats. , 1996, Neuroreport.

[16]  Y. Suzuki,et al.  Neonatal form of biotin-responsive multiple carboxylase deficiency. , 1992, Journal of nutritional science and vitaminology.

[17]  D. Mock.  Skin manifestations of biotin deficiency. , 1991, Seminars in dermatology.

[18]  B. Beaufrere,et al.  Le déficit en biotinidase: une maladie à expression neurologique et cutanée sensible à la biotine , 1989 .

[19]  M. Rolland,et al.  [Biotidinase deficiency: a disease with neurologic and cutaneous expression susceptible to biotin]. , 1989, Pediatrie.

[20]  B. Wolf,et al.  Biotinidase deficiency: Initial clinical features and rapid diagnosis , 1985, Annals of neurology.

[21]  P. Berlit,et al.  Biotin Status of Epileptics a , 1985, Annals of the New York Academy of Sciences.

[22]  D. Mock,et al.  Biotin deficiency complicating parenteral alimentation: diagnosis, metabolic repercussions, and treatment. , 1985, Annals of the New York Academy of Sciences.

[23]  W. Nyhan,et al.  Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. , 1985, American journal of human genetics.

[24]  W. Parker,et al.  Phenotypic variation in biotinidase deficiency. , 1983, The Journal of pediatrics.

[25]  C. L. Kien,et al.  Biotin deficiency with neurologic and cutaneous manifestations but without organic aciduria. , 1983, The Journal of pediatrics.

[26]  B. Wolf,et al.  Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. , 1983, Clinica chimica acta; international journal of clinical chemistry.

[27]  M. Williams,et al.  Alopecia and periorificial dermatitis in biotin-responsive multiple carboxylase deficiency. , 1983, Journal of the American Academy of Dermatology.

[28]  W. Parker,et al.  Deficient biotinidase activity in late-onset multiple carboxylase deficiency. , 1983, The New England journal of medicine.

[29]  P. Berlit,et al.  Imparied biotin status in anticonvulsant therapy , 1982, Annals of neurology.

[30]  B. Robinson,et al.  Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. , 1982, The Journal of pediatrics.

[31]  A. Munnich,et al.  Search for the biochemical basis of biotin dependent multiple carboxylase deficiencies: determination of biotin activation in cultured fibroblasts. , 1982, Clinica chimica acta; international journal of clinical chemistry.

[32]  S. Packman,et al.  PRENATAL TREATMENT OF BIOTIN-RESPONSIVE MULTIPLE CARBOXYLASE DEFICIENCY , 1982, The Lancet.

[33]  C. McClain,et al.  Biotin deficiency in an adult during home parenteral nutrition. , 1982, JAMA.

[34]  K. Dakshinamurti,et al.  Prenatal Administration of Biotin in Biotin Responsive Multiple Carboxylase Deficiency , 1982, Pediatric Research.

[35]  W. Nyhan,et al.  Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency. , 1981, The Journal of clinical investigation.

[36]  S. Packman,et al.  Biotin-responsive multiple carboxylase deficiency of infantile onset. , 1981, The Journal of pediatrics.

[37]  G. Feldman,et al.  Biochemical characterization of biotin-responsive multiple carboxylase deficiency: heterogeneity within the bio genetic complementation group. , 1981, American journal of human genetics.

[38]  B. Wolf,et al.  Deficient acetyl CoA carboxylase activity in multiple carboxylase deficiency. , 1981, Clinica chimica acta; international journal of clinical chemistry.

[39]  K. Dakshinamurti,et al.  Serum and urinary biotin levels during treatment of holocarboxylase synthetase deficiency. , 1981, Clinica chimica acta; international journal of clinical chemistry.

[40]  S. Packman,et al.  Intermittent ataxia and immunodeficiency with multiple carboxylase deficiencies: A biotin‐responsive disorder , 1980, Annals of neurology.

[41]  K. Roth,et al.  Holocarboxylase synthetase deficiency: a biotin-responsive organic acidemia. , 1980, The Journal of pediatrics.

[42]  W. Nyhan,et al.  Propionyl-CoA Carboxylase Deficiency in a Patient with Biotin-responsive 3-Methylcrotonylglycinuria , 1977, Pediatric Research.

[43]  Bonjour Jp.  Biotin in man's nutrition and therapy -- a review. , 1977 .

[44]  J. Bonjour.  Biotin in man's nutrition and therapy -- a review. , 1977, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[45]  G. Draffan,et al.  BIOTIN-RESPONSIVE β-METHYLCROTONYLGLYCINURIA , 1971 .

[46]  G. Draffan,et al.  Biotin-responsive beta-methylcrotonylglycinuria. , 1971, Lancet.

[47]  M. Hardinge,et al.  Lesser known vitamins in foods. , 1961, Journal of the American Dietetic Association.

[48]  D. Scott.  Clinical biotin deficiency (egg white injury); report of a case with some remarks on serum cholesterol. , 2009, Acta medica Scandinavica.

[49]  A. Tornberg.  Determination of T-1824 (Evans blue dye) in lipemia and hemolysis with a modified extraction method. , 2009, Acta medica Scandinavica.

[50]  A. Bayle.  PHYSIOLOGY AND PATHOLOGY OF THE NERVOUS SYSTEM , 1824 .