The symptoms, biochemical features and inheritance pattern of partial biotinidase deficiency have been studied at the Departments of Human Genetics and Pediatrics, Medical College of Virginia, Richmond, VA; the State Laboratory Institute, Massachusetts Department of Public Health; Massachusetts General Hospital, Boston; the Lincoln Clinic, NB; and the Division of Human Genetics, university of Maryland School of Medicine, Baltimore. Twelve boys and four girls identified by newborn screening had partial biotinidase deficiency, defined as 10% to 30% of the mean normal activity. Three siblings of these children also had partial deficiency. Fourteen children ascertained by neonatal screening had profound biotinidase deficiency (less than 10% mean normal activity). Two siblings with profound deficiency were found among older siblings of these children. In 24 children with symptoms biotinidase activity levels were less than 10% of the mean normal level. All children with partial deficiency were healthy at the time of diagnosis. One child not treated initially with biotin later developed hypotonia, hair loss and skin rash which resolved with biotin therapy. Delayed development of symptoms in some cases may depend on the interaction of reduced biotinidase activity with other factors. e.g. availability of exogenous biotin and alterations in metabolic demand for the vitamin. The need for biotin supplementation may be increased at times of infection and stress. [1]

COMMENT. Biotin responsive late onset multiple carboxylase deficiency is an autosomal recessive inherited disorder manifested by seizures, alopecia, skin rash, hypotonia, ataxia, hearing loss, and developmental delay. Lactic acidosis and organic aciduria are often present and if untreated the symptoms become progressively worse and coma and death may occur. Symptoms of biotinidase deficiency resolve rapidly after treatment with biotin 5-10 mg daily orally, but neurologic damage may be irreversible. Early diagnosis and treatment of partial biotinidase deficiency may prevent the development of potentially serious consequences.