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)

Ten patients with biotinidase deficiency were studied. Clinical findings at presentation varied with dermatological signs (dermatitis and alopecia), neurological abnormalities (fits, hypotonia, and ataxia), and recurrent infections being the most common features, although none of these occurred in every case. Biochemically the disease is characterised by metabolic acidosis and organic aciduria. Treatment with biotin results in pronounced, rapid, clinical and biochemical improvement, but some patients have residual neurological damage comprising neurosensory hearing loss, visual pathway defects, ataxia, and mental retardation. The cause of this permanent damage remains obscure and it is not clear if the early introduction of treatment will prevent it.
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PMID:Biotinidase deficiency: a survey of 10 cases. 319 50

Biotin deficiency associated with total parenteral nutrition is an emerging clinical problem; criteria for diagnosis and dosage for treatment are unclear. We have diagnosed and successfully treated biotin deficiency in three patients. Each patient had alopecia totalis, hypotonia, and developmental delay. Two developed the characteristic scaly periorificial dermatitis; one had only an intermittent scaly rash on the cheeks and occipital scalp. Zinc and essential fatty acid supplements were adequate; serum zinc levels and triene/tetraene ratios confirmed sufficiency of these nutrients. None of the patients received biotin prior to diagnosis, and each had decreased excretion of urinary biotin and increased urinary excretion of organic acids diagnostic of deficiency of two biotin-dependent enzymes (methylcrotonyl-coenzyme A carboxylase and priopionyl-coenzyme A carboxylase). Only one patient had a plasma biotin concentration below the normal range (Ochromonicas danica assay). The rash, alopecia, and neurologic findings responded dramatically to biotin therapy (100 micrograms/day in all patients; an initial larger dose of 1 mg/day for 1 week plus 10 mg/day for 7 weeks in one patient), and did not recur. However, abnormal organic acid excretion persisted in one patient who did not receive the larger dose. We conclude that plasma biotin concentration does not reflect biotin status in all cases and speculate that the biotin supplement currently recommended for pediatric patients (20 micrograms/day) may not be adequate therapy for biotin deficiency and might not even be adequate to maintain normal biotin status during TPN.
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PMID:Biotin deficiency complicating parenteral alimentation: diagnosis, metabolic repercussions, and treatment. 392 77

Two patients presented in early childhood with: 1) alopecia, skin rashs, and candida dermatitis; 2) severe hypotonia, ataxia and motor retardation; 3) frequent episodes of ketoacidosis with hyperlactacidemia. Propionic and methylcrotonic aciduria only appeared on hyperprotidic diet. Mitochondrial biotin-dependent carboxylase activities were decreased in the liver and leukocytes, but were paradoxically normal in cultured fibroblasts whatever the biotin content of the medium. These disorders responded to biotin administration, pointing to multiple biotin-dependent carboxylase deficiencies (MCD). Our report stresses the polymorphism of MCD: major discrepancies concern predominance of carboxylase deficiency, expression of MCD in cultured fibroblasts, and possible involvement of a cytoplasmic biotin enzyme, acetyl CoA carboxylase (ACC). Finally, we suggest that MCD could be of two types: impaired biotin metabolism (absorption, transport, activation) might result in generalization MCD involving ACC. Defective holocarboxylase synthetase might lead to a pure mitochondrial MCD with fibroblastic deficiency and presumably skin integrity.
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PMID:[Multiple biotin-dependent carboxylase deficiencies (author's transl)]. 611 72

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. Propionic and methylcrotonic aciduria only appeared on high protein diet. Mitochondrial biotin-dependent carboxylase activities were decreased in the liver and leukocytes, but were similar to control values in fibroblasts cultured in a biotin-free medium. In addition, the plasma biotin was found to be significantly lower than in control subjects. These disorders responded to biotin administration, pointing to biotin-dependent multiple carboxylase deficiencies (MCD). Our report stresses the polymorphism of MCD and suggests that MCD could be of two types: impaired vitamin metabolism (absorption, plasma transport), might result in low plasma biotin with generalized MCD involving acetyl CoA carboxylase. Defective mitochondrial holocarboxylase synthetase might lead to a pure mitochondrial MCD, with fibroblastic deficiency and presumably normal biotin metabolism.
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PMID:Biotin dependent multiple carboxylase deficiency presenting as a congenital lactic acidosis. 719 43

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

An unusual presentation of biotinidase deficiency is described. The disorder classically presents in infancy or early childhood with intractable seizures, hypotonia, ataxia, hearing loss, dermatitis, and alopecia. A 5-year-old girl developed acute visual loss associated with optic atrophy, and disturbance of gait with predominantly lower-limb pyramidal signs. She had no seizures, and skin, hair, hearing, and intellect were normal. Biotinidase deficiency was confirmed biochemically and she responded well to biotin therapy. A diagnosis of biotinidase deficiency should be considered in children with unexplained bilateral optic neuropathy, particularly when there is accompanying gait disorder.
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PMID:Late presentation of biotinidase deficiency with acute visual loss and gait disturbance. 943 60

We report a case of partial biotinidase deficiency (plasma biotinidase levels: 1.30 nm/minute/mL) in a 7-month-old boy who presented with evidence of perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. His neurologic symptoms improved markedly on biotin supplementation and antiepileptic drug therapy. DNA mutational analysis revealed that the patient was homozygous for a novel E64K mutation and his parents were heterozygous for the same mutation. Whereas preexisting perinatal distress probably contributed to the severity of the patient's symptoms, the described mutation is novel and is possibly responsible for at least some of his clinical manifestations.
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PMID:Novel mutation causing partial biotinidase deficiency in a Syrian boy with infantile spasms and retardation. 1709 67

Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids and glucose. Carboxylase activities decrease substantially in response to biotin deficiency. Biotin is also covalently attached to histones; biotinylated histones are enriched in repeat regions in the human genome and appear to play a role in transcriptional repression of genes and genome stability. Biotin deficiency may be caused by insufficient dietary uptake of biotin, drug-vitamin interactions and, perhaps, by increased biotin catabolism during pregnancy and in smokers. Biotin deficiency can also be precipitated by decreased activities of the following proteins that play critical roles in biotin homeostasis: the vitamin transporters sodium-dependent multivitamin transporter and monocarboxylate transporter 1, which mediate biotin transport in the intestine, liver and peripheral tissues, and renal reabsorption; holocarboxylase synthetase, which mediates the binding of biotin to carboxylases and histones; and biotinidase, which plays a central role in the intestinal absorption of biotin, the transport of biotin in plasma and the regulation of histone biotinylation. Symptoms of biotin deficiency include seizures, hypotonia, ataxia, dermatitis, hair loss, mental retardation, ketolactic acidosis, organic aciduria and also fetal malformations. This review focuses on the deficiencies of both biotin and biotinidase, and the medical management of such cases.
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PMID:Biotin and biotinidase deficiency. 1972 38