Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biotinidase deficiency is the primary defect in most individuals with late-onset multiple carboxylase deficiency. We have reviewed the presenting clinical features of 31 children with the disorder. Seizures, either alone or with other neurological or cutaneous findings, are the most frequent initial symptom observed. Other neurological symptoms, such as hypotonia, ataxia, hearing loss, optic atrophy, and developmental delay, are seen, in addition to skin rash and alopecia. The disorder is also characterized by ketolactic acidosis and organic aciduria. Biotinidase activity may be diagnosed using a simple, rapid, semiquantitative colorimetric procedure. Samples of whole blood spotted on the same filter paper used by most states to screen for phenylketonuria and other inborn errors of metabolism may be sent to an appropriate reference laboratory. None of the common anticonvulsants or sedatives used to treat newborns and children interfere with the test. Because biotinidase deficiency can be treated readily with biotin, this disorder should be considered in children with infantile seizures, especially in the presence of other characteristic neurological or cutaneous features.
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PMID:Biotinidase deficiency: initial clinical features and rapid diagnosis. 407 53

There are two genetically determined biotin-dependent disorders. The first is holocarboxylase synthetase (HCS) deficiency and the second biotinidase deficiency. HCS catalyzes the reaction in which active holocarboxylases are synthesized from inactive apocarboxylases. Biotin is required for this synthesis. Biotinidase facilitates the release and recycling of free biotin. Deficiency of either HCS or biotinidase is characterized by certain neurological, cutaneous and biochemical abnormalities. In this paper, six patients with biotinidase and two patients with HCS deficiency are described. Among the most common neurological findings were hypotonia (6/8), seizures (2/6) and optic atrophy (2/8). Dermatitis and conjunctivitis were present in three and four patients, respectively. All patients had low blood pH bicarbonate levels. Serum lactate was increased in all and pyruvate in six cases. Two patients with biotinidase deficiency presented earlier than the mean age of onset previously reported in the literature. Detection of eight cases during the past few years at a single metabolic unit indicates that biotinidase deficiency is not rare in Turkey, where the frequency of some other metabolic disorders has also been reported to be high. We suggest that biotin-dependent disorders should be considered in all infants with neurological symptoms, particularly those with jerks, even if other signs such as alopecia, seborrheic dermatitis and acidosis are not evident, regardless of the age of presentation.
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PMID:Inborn errors of biotin metabolism. Clinical and laboratory features of eight cases. 782 32

Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disease, which develops neurological and cutaneous symptoms because of the impaired biotin recycling. Pathogenic mutations on BTD gene cause BTD deficiency. Clinical features and mutation analysis of Chinese children with BTD deficiency were rarely described. Herein, for the first time, we reported the clinical features, BTD gene mutations and their functional studies of eight symptomatic children with BTD deficiency from southern China. Fatigue, hypotonia, proximal muscular weakness, hearing deficits, rash and respiratory problems are common clinical phenotype of our patients. Seizures are observed only in patients with profound BTD deficiency. Five novel mutations were detected, among which c.637delC (H213TfsTer51) was found in 50% of our patients and might be considered as a common mutation. In vitro studies confirmed three mild mutations c.1368A>C (Q456H), c.1613G>A (R538H), and c.644T>A (L215H) which retained 10-30% of wild type enzyme activity, and six severe mutations c.235C>T (R79C), c.1271G>C (C424S), c.1412G>A (C471Y), c.637delC (H213TfsTer51), c.395T>G (M132W), c.464T>C (L155P), and c.1493dupT (L498FfsTer13) which retained <10% of wild type enzyme activity. c.1330G>C (D444H) decreased the protein expression but not activity of BTD enzyme, and H213TfsTer51 was structurally damaging while L498FfsTer13 was functionally damaging. These results will be helpful in establishing the definitive diagnosis of BTD deficiency at the gene level, offering appropriate genetic counseling, and providing clues to structure/function relationships of the enzyme.
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PMID:Clinical features, BTD gene mutations, and their functional studies of eight symptomatic patients with biotinidase deficiency from Southern China. 2935 54