Two patients with biotin-responsive multiple carboxylase deficiency, both presenting with predominant lactic acidosis, are reported. [ncbi.nlm.nih.gov]

Untreated patients and those with less severe defects present with mental retardation, hair loss, and skin lesions (erythematous rash often with superinfection with Candida). Deficiency of biotinidase presents later in infancy or childhood. [accessanesthesiology.mhmedical.com]

Both enzyme deficiencies present overlapping clinical manifestations. However, the biotinidase deficiency results in total alopecia and ataxia. Both diseases present a picture of severe organic acidaemia. [bhj.org.in]

• Turkish

  Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. Eur. J. Pediatr. 2015; :None. PMID: 25754625 Neto, EC, et al. [invitae.com]

• Movement Disorder

  94 Paroxysmal Dyskinesias E-1637 95 Movement Disorders of Infancy E-1646 96 DrugInduced Movement Disorders in Children E-1651 97 Cerebral Palsy E-1660 98 Tics and Tourette Syndrome E-1673 99 Genetic and Metabolic Disorders of the White Matter E-1690 100 [books.google.com]

  Disorders Society Disclosure: Nothing to disclose. [emedicine.medscape.com]

• Surgical Procedure

  In addition, combination therapy with both recombinant activated FVII (eptacog alfa) and vitamin K supplementation may constitute an alternative treatment option for surgical procedures and severe manifestations. [orpha.net]

• Fever

  Difficulty breathing Alopecia Motor skill delays Hearing loss Speech loss Spasticity Problems with coordination Seizures Brain damage Death Treatment consists of biotin at high doses (20-300 mg per day), fasting avoidance and prompt treatment of infections, fever [medicalhomeportal.org]

• Fatigue

  However, the causative attribution of all other clinical signs, especially of unspecific chronic neurologic symptoms such as mental retardation, attention deficit disorders and fatigue to MCC deficiency remains questionable. [ojrd.biomedcentral.com]

• Vomiting

  Individuals with the disorder usually exhibit poor appetite, vomiting, lethargy, irritability, hypotonia and exfoliative dermatitis. Metabolically, they have ketolactic acidosis, organic acidemia (-uria) and hyperammonemia. [orpha.net]

  Clinical considerations: Poor feeding, vomiting, lethargy, tachypnea Ketonuria Metabolic ketoacidosis Hyperammonemia Hypoglycemia Referral: If signs are present or infant is ill, check urine ketones and initiate emergency treatment with start IV glucose [archildrens.org]

  These infants present with poor feeding, vomiting, lethargy, coma and seizures. The urine has the strong odor of a cat’s urine. [dermatologyadvisor.com]

  Primary Care Management Upon Notification of the + Screen Contact the family and evaluate the infant for poor feeding, vomiting, or lethargy. [medicalhomeportal.org]

• Failure to Thrive

  […] to thrive, seizure, coma, developmental delay, foul smelling urine, lactic acidosis, and high levels of ketones and ammonia in the blood. [en.wikipedia.org]

  […] to thrive, seizure, coma, developmental delay, foul smelling urine, metabolic acidosis, ketosis and hyperammonemia. [ipfs.io]

  Partial MethylCrotonyl-CoA Carboxylase Deficiency in an infant with failure to thrive, gastrointestinal dysfunction and hypertonia. Pediatrics 91:664, 1993. Elpeleg, O.N., Havkin, S., Barash, V., et al. [path.upmc.edu]

  They present with tachypnea, feeding difficulties, hypotonia, generalized eczematous rash with exfoliation and alopecia (partial or total), failure to thrive and seizures.[4] They are usually catastrophically ill with severe metabolic acidosis, lactic [ncbi.nlm.nih.gov]

• Alopecia

  There was diffuse alopecia, seborrheic dermatitis and perioral desquamating lesions [Figure 1]. Bilateral Babinski was positive, jerks were brisk (grade 3) in all four limbs. [ncbi.nlm.nih.gov]

  Abstract: Late-onset multiple carboxylase deficiency is characterized clinically by skin rash, alopecia, seizures and ataxia and occasionally by candidiasis and developmental delay. [deepblue.lib.umich.edu]

• Skin Rash

  Abstract: Late-onset multiple carboxylase deficiency is characterized clinically by skin rash, alopecia, seizures and ataxia and occasionally by candidiasis and developmental delay. [deepblue.lib.umich.edu]

  Two patients presented in early childhood with (i) alopecia, skin rashs, and dermatitis, (ii) severe hypotonia, ataxia and motor retardation, (iii) frequent episodes of ketoacidosis with hyperlactacidemia. [ncbi.nlm.nih.gov]

  Affected infants often have immunodeficiency diseases, difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). [checkorphan.org]

• Eczema

  Eczema, alopecia, dermatitis, and skin infections are also common findings, and cutaneous presentations in conjunction with neurological symptoms greatly limit the differential diagnosis. Clinical variability is documented. [preventiongenetics.com]

  Some other common features of BTD include eye infections, like pink eye (conjunctivitis), hair loss (alopecia), and a certain type of skin rash called eczema. [rarediseases.org]

  Untreated patients with profound biotinidase deficiency can have hypotonia, seizures, alopecia, eczema, and developmental delay. [invitae.com]

Timely and ongoing treatment makes it possible to reduce symptoms considerably, although some patients develop complications despite appropriate treatment often requiring higher doses of biotin. [orpha.net]

TREATMENT Immediate diagnosis and treatment of multiple carboxylase deficiency is critical to normal growth and development. Treatment is usually effective if started early. Recommended treatment is daily supplementation of biotin. [fr.slideshare.net]

It is also not a consequence of feedback control in affected individuals under treatment with pharmacologie doses of biotin. [deepblue.lib.umich.edu]

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. [ncbi.nlm.nih.gov]

[…] enteropathica (p. 328) Mucocutaneous candidiasis Essential fatty acid deficiency Lab Screen urine for organic aciduria Serum biotinidase/holocarboxylase synthetase assay Screen blood metabolic acidosis, hyperammonemia Management Biotin 10 mg per day for life Prognosis [cram.com]

Both types of multiple carboxylase deficiency respond dramatically to treatment with oral bioin and prognosis is good if the condition is diagnosed and treated early. [sas-centre.org]

The clinical heterogeneity, taken together with the distinct responses of cultured skin fibroblasts to biotin deprivation in vitro, probably reflect fundamentally different etiologies for the two categories of biotin-responsive multiple carboxylase deficiency [ncbi.nlm.nih.gov]

Etiology Biotinidase deficiency is caused by mutations in the BTDgene (3p25) and holocarboxylase synthetase deficiency by mutations in the HLCS gene (21q22.1). Genetic counseling Both disorders are inherited as autosomal recessive traits. [rarediseases.info.nih.gov]

Etiology Holocarboxylase synthetase deficiency is caused by mutations in the HLCS gene (21q22.1) resulting in reduced HCS activity. [orpha.net]

Epidemiology The prevalence of MCD is unknown, but the condition is rare. There is no specific geographic or ethnic predominance. [rarediseases.info.nih.gov]

Summary Epidemiology The exact prevalence of HCSD is unknown, but the condition is one of the rarest inborn errors of metabolism. Annual incidence is estimated to be less than 1/200,000 live births. [orpha.net]

Relevant External Links for EIF2B4 Genetic Association Database (GAD) EIF2B4 Human Genome Epidemiology (HuGE) Navigator EIF2B4 Atlas of Genetics and Cytogenetics in Oncology and Haematology: EIF2B4 No data available for Genatlas for EIF2B4 Gene Use of [genecards.org]

Immunologic dysfunction and/or aberration in lipid or branched chain amino acid metabolism may be the common pathophysiologic link in some or all of these disorders. [ncbi.nlm.nih.gov]

Pathophysiology The gene for olocarboxylase synthetase is located on chromosome 21q22.1 and has 11 exons. There are at least 35 mutations known. The gene for biotinidase deficiency (BPD) is located on chromosome 3p25 and has 4 axons. [dermatologyadvisor.com]

Despite its rarity, early recognition is imperative because expeditious treatment may prevent or minimize clinical insult. [8] Pathophysiology Biotin is one of the water-soluble B-complex vitamins. [9] This imidazole derivative [9] is present in various [emedicine.medscape.com]

Children lacking biotinidase activity are unable to recycle biotin, and are thus entirely dependent upon exogenous biotin to prevent deficiency. [deepblue.lib.umich.edu]

Mutations in the HLCS gene reduce the enzyme's ability to attach biotin to these enzymes, preventing them from processing nutrients properly and disrupting many cellular functions. [ghr.nlm.nih.gov]

Mutations in the HLCS gene reduce the activity of holocarboxylase synthetase, preventing cells from using biotin effectively and disrupting many cellular functions. [en.wikipedia.org]

Prevention - Multiple carboxylase deficiency- biotin responsive Not supplied. [checkorphan.org]