Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two children with biotinidase deficiency presented with seizures at 2 months of age. The first child had a fluctuating course with continual developmental progress and cessation of seizures despite symptoms of chronic neurologic dysfunction until he was diagnosed at 17 months. The second child had a progressive course with uncontrolled seizures leading to an unresponsive state until she was diagnosed at 6 1/2 months. Neither child had dermatologic symptoms until shortly before the time of diagnosis. Both children improved markedly with biotin treatment. Serial CT-scan and MRI studies of the brain showed a distinct pattern of changes. Shortly after initial presentation, diffuse low attenuation of the white matter was seen followed by progressive marked cerebral atrophy, which was reversed following biotin treatment. Because this is a reversible condition, clinicians should screen for biotinidase deficiency in all children with symptoms of chronic neurologic dysfunction, especially when radiologic findings of low attenuation of the white matter are followed by cerebral atrophy.
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PMID:Reversal of brain atrophy with biotin treatment in biotinidase deficiency. 823 80

Biotinidase deficiency is an autosomal recessively inherited disorder that is often characterized by neurologic abnormalities. We reviewed the clinical features of 78 symptomatic children, 11 new patients and 67 previously reported cases, to determine the frequency, type, age at onset, and the responsiveness of seizures to antiepileptic drugs and biotin therapy. Forty-three of the 78 (55%) symptomatic children had seizures, and seizures were the presenting symptom in 38% of the enzyme-deficient patients and 70% of those who had had seizures at some time. EEGs were available for 21 of these children. Sixteen were abnormal. The initially abnormal EEGs in eight of 12 infants became normal or improved with biotin therapy, whereas four continued to be abnormal. In 21 (49%) patients, the seizures were not well controlled with antiepileptic drugs. Biotin therapy stopped the seizures within 24 hours in 12 of 16 (75%) of those whose seizures were uncontrolled by anticonvulsants (five children died prior to diagnosis). Although the metabolic and cutaneous abnormalities were corrected in the remaining four children, they continued to have neurologic abnormalities. Biotinidase deficiency and a trial of biotin (5 to 10 mg) should be considered in infants less than 1 year of age with poorly controlled seizures, and biotinidase deficiency should be included in the differential diagnosis of an infant or child with unexplained seizures.
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PMID:Characterization of seizures associated with biotinidase deficiency. 832 37

Biotin-deficient conditions are frequently associated with epileptic disorders. Biotin deficiency may be caused by long-term treatment with anticonvulsants or excessive ingestion of avidin. Absence of biotinidase activity can also lead to biotin deficiency, and is characterized by developmental delay as well as neurological and dermatological abnormalities. Because seizures are one of the most frequent signs of the latter, biotin-deficient conditions could conceivably facilitate convulsive disorders. To test this hypothesis, we investigated the occurrence of a latent kindling hyperexcitability in biotin-deprived rats. In these animals, duration of after-discharge on the first stimulation was longer at threshold amplitude, kindling development through its early stages was accelerated and duration of the forelimb clonus of fully kindled seizures was increased. Biotin deprivation in mixed cerebellar granule cell-astrocyte cultures also produced a tetrodotoxin-sensitive delayed loss of the glutamatergic neuronal population. The data thus support a facilitatory role for biotin-deficient conditions in convulsive disorders.
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PMID:Biotin deficiency facilitates kindling hyperexcitability in rats. 890 56

Acquired biotin deficiency and the two known congenital disorders of biotin metabolism, biotinidase and holocarboxylase synthetase (HCS) deficiency, all lead to deficiency of the 4 biotin-dependent carboxylases, i.e. to multiple carboxylase deficiency (MCD). The underlying mechanism in HCS-deficiency, discovered in 1981, is decreased affinity of HCS for biotin impairing the formation of holocarboxylases at physiological biotin levels. In biotinidase deficiency, discovered in 1983, MCD results from progressive development of biotin-deficiency due to inability to liberate and recycle biotin which is lost in urine as biocytin. MCD leads to typical organic aciduria and severe life-threatening illness. Main symptoms and signs are feeding difficulties, neurologic abnormalities (hypotonia, impaired consciousness, seizures, ataxia) and cutaneous changes (rash, alopecia). However, the clinical presentation and age of onset are extremely variable, and organic aciduria may initially be absent in biotinidase deficiency. Therefore, the definitive diagnosis requires enzyme studies. MCD can be detected in lymphocytes obtained before treatment and biotinidase deficiency is confirmed or excluded by a colorimetric enzyme assay in plasma. Newborn screening for biotinidase deficiency has resulted in the detection of patients with partial deficiency (10-30% of mean normal activity) in addition to patients with profound deficiency (0-10%). Severe illness has been observed mainly in patients with O-activity or a Km-mutation, detection of which requires detailed investigation. HCS-deficiency has to be confirmed by enzyme assay in cultured cells. Both congenital disorders respond clinically and biochemically to oral biotin therapy. Whereas 10 mg/day or less is sufficient to treat profound biotinidase deficiency, the optimal biotin dose for patients with HCS-deficiency must be assessed individually. The prognosis of both disorders is good if biotin therapy is introduced early and continued throughout life. However, delayed commencement of therapy in biotinidase deficiency can result in irreversible neurological damage, and in HCS-deficiency a few patients have responded only partially even to massive biotin doses of up to 100 mg/day.
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PMID:Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. 935 Apr 81

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

Biotinidase deficiency and holocarboxylase synthetase deficiency are two autosomal recessively inherited disorders of biotin metabolism affecting children below the age of two years. Both cause multiple carboxylase deficiency resulting in defects of fatty acid synthesis, gluconeogenesis and amino acid catabolism. The clinical picture involves the nervous system, the skin, the respiratory system, the digestive system and the immune system, but great individual variations often makes the clinical diagnosis difficult. Early diagnosis and treatment with biotin are essential in order to prevent death from metabolic acidosis or irreversible damage to the central nervous system. Two patients with biotinidase deficiency, two patients with holocarboxylase synthetase deficiency and a review of the literature are presented. Neonatal screening for biotinidase deficiency or a higher degree of metabolic screening of the urine in children below the age of one year with seizures and unexplained clinical course are discussed.
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PMID:[Multiple carboxylase deficiency]. 949 25

Biotinidase deficiency is a well recognised treatable cause of a wide spectrum of progressive neurological symptoms. Recent reports have stressed the need to screen children with early onset of seizures, encephalopathy, neurodevelopmental delay, skin rash and alopecia. Enzyme estimation remains the conclusive test. We present a patient with biotinidase deficiency suspected on the above clinical grounds and diagnosed on the basis of metabolic acidosis, raised blood lactate, ketonuria and positive dinitrophenylhydrazine (DNPH) test and confirmed on urinary organic acid profile. Supplementation with biotin resulted in marked clinical improvement and normalisation of metabolic parameters. Thus the clinician should be alert to simple clinical pointers which aid in early diagnosis of these disorders.
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PMID:Biotinidase deficiency--a treatable entity. 1093 69

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

Biotinidase deficiency is an autosomal recessively inherited disorder that manifests during childhood with various cutaneous and neurological symptoms particularly seizures, hypotonia, and developmental delay. Spinal cord disease has been reported rarely. We describe a 3-year-old boy with profound biotinidase deficiency who presented with progressive spastic paraparesis and ascending weakness in the absence of the usual characteristic neurological manifestations. Supplementation with biotin resulted in resolution of paraparesis with persistent mild spasticity in the lower limbs. DNA mutation analysis revealed that he was homozygous for a novel missense mutation (C>T1339;H447Y) in the BTD gene. This case indicates that biotinidase deficiency should be included in the differential diagnosis of subacute myelopathy and emphasizes the importance of a prompt diagnosis to prevent irreversible neurological damage.
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PMID:Profound biotinidase deficiency in a child with predominantly spinal cord disease. 1864 4

Infantile spasms are an epilepsy syndrome with distinctive features, including age onset during infancy, characteristic epileptic spasms, and specific electroencephalographic patterns (interictal hypsarrhythmia and ictal voltage suppression). Adrenocorticotropic hormone (ACTH) was first employed to treat infantile spasms in 1958, and since then it has been tried in prospective and retrospective studies for infantile spasms. Oral corticosteroids were also used in a few studies for infantile spasms. Variable success in cessation of infantile spasms and normalization of electroencephalograms was demonstrated. However, frequent significant adverse effects are associated with ACTH and oral corticosteroids. Vigabatrin has been used since the 1990s, and shown to be successful in resolution of infantile spasms, especially for infantile spasms associated with tuberous sclerosis. It is associated with visual field constriction, which is often asymptomatic and requires perimetric visual field study to identify. When ACTH, oral corticosteroids, and vigabatrin fail to induce cessation of infantile spasms, other alternative treatments include valproic acid, nitrazepam, pyridoxine, topiramate, zonisamide, lamotrigine, levetiracetam, felbamate, ganaxolone, liposteroid, thyrotropin-releasing hormone, intravenous immunoglobulin and a ketogenic diet. Rarely, infantile spasms in association with biotinidase deficiency, phenylketonuria, and pyridoxine-dependent seizures are successfully treated with biotin, a low phenylalanine diet, and pyridoxine, respectively. For medically intractable infantile spasms, some properly selected patients may have complete cessation of infantile spasms with appropriate surgical treatments.
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PMID:Current trends in the treatment of infantile spasms. 1955 23


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