ABSTRACT
Holocarboxylase synthetase deficiency is typically a biotin responsive disorder that presents with lactic acidosis, tachypnea, temperature instability, and shock in neonates (Briones et al.1989 and Fuchshuber et al. 1992). The primary defect in cases studied to date appears to be the decreased affinity of HCS for its substrate, biotin (Gompertz et al. 1971). Supplemental biotin can provide sufficient substrate to increase HCS enzymatic function and thereby permit biotinylation of the four carboxylase apoenzymes (Briones et al. 1989). We report an infant with HCS deficiency who presented with lactic acidosis, shock, and hypertonia. Subependymal cysts were identified on cranial ultrasound and subsequently confirmed by MRI. Six months following biotin supplementation, she is developmentally normal and MRI of the brain shows complete resolution of the cysts.
Subject(s)
Brain Neoplasms/congenital , Carbon-Nitrogen Ligases , Glioma, Subependymal/congenital , Ligases/deficiency , Multiple Carboxylase Deficiency/complications , Biotin/therapeutic use , Brain Neoplasms/diagnosis , Cerebral Ventricles , Cysts , Female , Glioma, Subependymal/diagnosis , Humans , Infant, Newborn , Magnetic Resonance Imaging , Multiple Carboxylase Deficiency/drug therapy , Remission InductionSubject(s)
Nutrition Disorders/complications , Skin Diseases/etiology , Acrodermatitis/genetics , Anemia/etiology , Child , Child, Preschool , Diet , Humans , Infant, Newborn , Multiple Carboxylase Deficiency/complications , Nigeria , Parasitic Diseases/complications , Protein-Energy Malnutrition/complications , Socioeconomic Factors , Vitamin A Deficiency/complications , Vitamin B Deficiency/complications , Zinc/deficiencySubject(s)
Ammonia/blood , Isomerases/deficiency , Metabolism, Inborn Errors/metabolism , Methylmalonyl-CoA Mutase/deficiency , Multiple Carboxylase Deficiency/metabolism , Oxidoreductases Acting on CH-CH Group Donors , Oxidoreductases/deficiency , Oxo-Acid-Lyases/deficiency , Acidosis/etiology , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Isovaleryl-CoA Dehydrogenase , Metabolism, Inborn Errors/complications , Multiple Carboxylase Deficiency/complicationsABSTRACT
The important role of biotin in human physiology has been highlighted by the recognition of two newly discovered human inborn errors of the metabolism of biotin. The molecular defect in the neonatal-onset disease is in the enzyme holocarboxylase synthetase. The defect in the later infantile-onset disease is in the enzyme biotinidase. Both disorders present with impressive clinical manifestations involving the skin and hair. In the neonatal disease, alopecia totalis is associated with a bright red scaly total body eruption. In biotinidase deficiency, the alopecia is more patchy and the skin lesions resemble acrodermatitis enteropathica. Both disorders are complicated by recurrent episodes of life-threatening acidosis and massive ketosis.
Subject(s)
Biotin/metabolism , Carbon-Nitrogen Ligases , Metabolism, Inborn Errors/diagnosis , Amidohydrolases/deficiency , Amidohydrolases/genetics , Biotin/therapeutic use , Biotinidase , Humans , Infant , Infant, Newborn , Ligases/deficiency , Ligases/genetics , Metabolism, Inborn Errors/complications , Metabolism, Inborn Errors/metabolism , Multiple Carboxylase Deficiency/complications , Multiple Carboxylase Deficiency/diagnosis , Multiple Carboxylase Deficiency/metabolism , Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , Skin Diseases/diagnosis , Skin Diseases/etiologyABSTRACT
There are two distinct forms of multiple carboxylase deficiency. A neonatal onset form is due to deficiency of holocarboxylase-synthetase. A later onset form in which neurological abnormalities are seen as well as those of the skin and hair is due to biotinidase deficiency. It is the purpose of this report to describe a patient with biotinidase deficiency who presents bilateral optic atrophy. The dosage of biotinidase enzyme in the patient's serum and in other members of his family confirms the autosomal recessive transmission of this condition.
