RESUMO
ABSTRACT: A 19-year-old man presented with 3 years of gradually progressive, painless vision loss in both eyes. The ophthalmic examination showed bilateral diminished visual acuity, dyschromatopsia, and temporal optic nerve pallor. The neurological examination was consistent with a mild myelopathy with decreased pin-prick sensation starting at T6-T7 and descending through the lower extremities. Hyperreflexia was also present in the lower more than upper extremities. Infectious, inflammatory, and nutritional serum workup and cerebrospinal fluid analysis were both unrevealing. MRI of the brain and spinal cord showed abnormal T2 hyperintensity of the fornix, corpus callosum, optic nerves, and lateral columns of the cervical and thoracic spine, with diffusion restriction in the inferior-posterior corpus callosum and fornix. Biotinidase serum enzyme activity was tested and showed a decreased level of activity. Biotinidase gene testing showed a homozygous pathogenic variant, c.424C>A (p.P142T), confirming the diagnosis of biotinidase deficiency and prompting oral biotin supplementation. Three months after starting treatment, the patient's visual acuity, color vision, visual fields, and MRI spine abnormalities all improved significantly. Biotinidase deficiency is an important diagnostic consideration in patients with unexplained optic neuropathy and/or myelopathy.
Assuntos
Deficiência de Biotinidase , Imageamento por Ressonância Magnética , Doenças do Nervo Óptico , Doenças da Medula Espinal , Humanos , Masculino , Deficiência de Biotinidase/diagnóstico , Deficiência de Biotinidase/complicações , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/etiologia , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/etiologia , Adulto Jovem , Acuidade Visual/fisiologia , Medula Espinal/diagnóstico por imagemRESUMO
A 10-year-old girl initially diagnosed with functional visual loss was later diagnosed with progressive optic atrophy. Directed questioning at 13 years of age revealed difficulty hearing that had not been noted by the parents. Whole exome sequencing and subsequent metabolic testing confirmed biotinidase deficiency. Although biotinidase deficiency classically manifests in early childhood with multiple manifestations, such as seizures and failure to thrive, a delayed-onset form can present primarily as juvenile progressive optic atrophy. Early diagnosis is critical because biotin supplementation prevents disease and deterioration.
Assuntos
Deficiência de Biotinidase , Atrofia Óptica , Adolescente , Biotina/uso terapêutico , Biotinidase , Deficiência de Biotinidase/complicações , Deficiência de Biotinidase/diagnóstico , Deficiência de Biotinidase/tratamento farmacológico , Criança , Feminino , Humanos , Atrofia Óptica/diagnóstico , Atrofia Óptica/etiologia , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologiaRESUMO
La deficiencia de biotinidasa es una alteración metabólica autosómica recesiva, que afecta la escisión de biotina disminuyendo su reciclado. Estudios en familiares del caso índice encontraron que generalmente ambos padres son portadores y los hermanos presentan el gen alterado; solo los homocigotos tienen síntomas que varían según el grado de deficiencia. Las madres pueden tener deficiencia moderada y mantenerse asintomáticas. En un estudio que utiliza células humanas expuestas a deficiencia de biotina, disminuyó el crecimiento celular y contribuyó al desarrollo de paladar hendido. La deficiencia de biotina en embarazadas ocasiona malformaciones en los productos. En recién nacidos, la deficiencia de biotinidasa se ha relacionado con síndrome VACTERL y páncreas anular. Se presenta el caso de una lactante con deficiencia de biotinidasa y defecto congénito de anillo vascular que rodea y comprime tráquea y esófago, alterando la deglución y la respiración. La niña fue suplementada con biotina e intervenida, con excelentes resultados.
Biotinidase deficiency is an autosomal recessive metabolic disorder that affects the cleavage of biotin. Family studies of the index case found that both parents are usually carriers and siblings have the altered gene, but only homozygotes have manifestations that vary depending on the deficiency grade. Mothers may have moderate deficiency and be asymptomatic; biotin deficiency in pregnant women causes defects in children. In a study, using human cells exposed to biotin deficiency, cell growth decreased contributing to the development of cleft palate. In newborns, biotinidase deficiency has been associated with VACTERL syndrome and annular pancreas. The case of an infant with biotinidase deficiency and congenital defect of the vascular ring is presented. This defect surrounds and compresses the trachea and esophagus, disturbing swallowing and breathing. Infant was supplemented with biotin and surgically intervened with excellent results.
Assuntos
Feminino , Humanos , Lactente , Aorta Torácica/anormalidades , Deficiência de Biotinidase/complicações , Artéria Subclávia/anormalidades , EsôfagoRESUMO
Biotinidase deficiency is an autosomal recessive metabolic disorder that affects the cleavage of biotin. Family studies of the index case found that both parents are usually carriers and siblings have the altered gene, but only homozygotes have manifestations that vary depending on the deficiency grade. Mothers may have moderate deficiency and be asymptomatic; biotin deficiency in pregnant women causes defects in children. In a study, using human cells exposed to biotin deficiency, cell growth decreased contributing to the development of cleft palate. In newborns, biotinidase deficiency has been associated with VACTERL syndrome and annular pancreas. The case of an infant with biotinidase deficiency and congenital defect of the vascular ring is presented. This defect surrounds and compresses the trachea and esophagus, disturbing swallowing and breathing. Infant was supplemented with biotin and surgically intervened with excellent results.
Assuntos
Aorta Torácica/anormalidades , Deficiência de Biotinidase/complicações , Artéria Subclávia/anormalidades , Esôfago , Feminino , Humanos , LactenteRESUMO
Biotinidase deficiency may produce variable neurologic manifestations. Brainstem and spinal cord disease comprises an uncommon presentation of biotinidase deficiency. We describe a 7-year old boy with subacute progressive quadriplegia and "sighing" respirations. Severe biotinidase deficiency was established, and the patient demonstrated complete recovery with biotin supplementation. Genetic studies revealed presence of homozygous mutation in the BTD gene [c.133C>T (p.H447Y)]. Biotinidase deficiency should be considered in the differential diagnosis for subacute, long segment myelopathy, particularly with brainstem involvement. This entity is treatable; a high index of suspicion can be life-saving. We also review the literature on biotinidase deficiency presenting as spinal cord demyelinating disease.
Assuntos
Deficiência de Biotinidase/complicações , Doenças da Medula Espinal/etiologia , Deficiência de Biotinidase/patologia , Tronco Encefálico/patologia , Criança , Humanos , Masculino , Recidiva , Medula Espinal/patologia , Doenças da Medula Espinal/patologiaRESUMO
Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in epileptic patients. However, VPA has many side effects dose-dependent or non-dose-dependent. It is reported that VPA treatment may lead to biotin deficiency and low serum and liver tissue biotinidase enzyme activity (BEA). Major clinical manifestations in biotin deficiency are seborrheic dermatitis, dry skin, fine and brittle hair, and alopecia. We aimed to investigate the effects of biotin supplementation on serum and liver tissue BEA and alopecia during VPA therapy. Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA-B2, VPA, and control). Except the control group, all groups were administrated VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12h intervals two divided doses. VPA-B1 was administrated biotin dose of 6 mg/kg/d and VPA-B2 was administrated biotin dose of 0.6 mg/kg/d. In the third week of the study, we determined alopecia in the study groups. Alopecia was seen in the subjects of 13.3% of VPA-B1 (n=2), 13.3% of VPA-B2 (n=2), and 40% of VPA (n=6). But statistical significant effect on alopecia by biotin supplementation was not able to be determined between the study groups. In the control group, alopecia was not observed. The ratios of alopecia in the study groups were statistically higher than the control group (p=0.028). Itchiness was more obvious in the study groups compared with the control group. Serum biotin levels of the biotin supplemented groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control group). Serum biotin levels of the VPA group were lower than the control group. There were significant decreases in the levels of serum and liver tissue BEA of the study groups compared with the control group. In conclusion we showed that VPA usage reduced the serum and liver tissue BEA and impaired the biotin utilization by affecting the liver. Partial biotinidase deficiency may lead to alopecia. It might be prevented by biotin supplementation in the patients receiving VPA therapy. We considered that further studies are necessary to find out the effective and safe biotin dose.
Assuntos
Alopecia/tratamento farmacológico , Deficiência de Vitaminas/tratamento farmacológico , Biotina/deficiência , Biotina/farmacologia , Deficiência de Biotinidase/tratamento farmacológico , Ácido Valproico/toxicidade , Alopecia/induzido quimicamente , Alopecia/metabolismo , Animais , Anticonvulsivantes/toxicidade , Deficiência de Vitaminas/induzido quimicamente , Deficiência de Vitaminas/complicações , Biotina/uso terapêutico , Biotinidase/sangue , Biotinidase/efeitos dos fármacos , Deficiência de Biotinidase/induzido quimicamente , Deficiência de Biotinidase/complicações , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Esquema de Medicação , Epilepsia/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/fisiopatologia , Masculino , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
A three month old baby presented with refractory seizures, dermatosis and persistent metabolic acidosis. Biotinidase deficiency was diagnosed on enzyme assay. Patient responded dramatically to biotin supplementation.
Assuntos
Deficiência de Biotinidase , Acidose/etiologia , Alopecia/etiologia , Biotina/uso terapêutico , Deficiência de Biotinidase/complicações , Deficiência de Biotinidase/diagnóstico , Deficiência de Biotinidase/tratamento farmacológico , Dermatite Seborreica/etiologia , Epilepsia/etiologia , Humanos , Lactente , MasculinoRESUMO
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.
Assuntos
Biotina/metabolismo , Deficiência de Biotinidase/complicações , Deficiência de Biotinidase/genética , Predisposição Genética para Doença/genética , Doenças da Medula Espinal/enzimologia , Doenças da Medula Espinal/genética , Biotina/administração & dosagem , Deficiência de Biotinidase/fisiopatologia , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Precoce , Regulação Enzimológica da Expressão Gênica/genética , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Masculino , Mutação de Sentido Incorreto/genética , Paraparesia Espástica Tropical/enzimologia , Paraparesia Espástica Tropical/genética , Paraparesia Espástica Tropical/fisiopatologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Doenças da Medula Espinal/fisiopatologia , Resultado do TratamentoRESUMO
Biotinidase deficiency is a treatable cause of severe neurological disorders and skin problems. Spinal cord impairment is a rare complication of this disease and is commonly unrecognized. The authors encountered 3 Chinese patients with progressive spinal cord demyelination associated with biotinidase deficiency. Case 1 exhibited fatigue, proximal muscular weakness, and hypotonic paraplegia from the age of 7 years 4 months. Demyelination of cervical and thoracic cord was evident on magnetic resonance imaging (MRI). Case 2 developed visual impairment, blepharoconjunctivitis, and optic nerve atrophy from 5 years of age, which combined with progressive hypertonic paralysis, ataxia, and alopecia from the age of 7 years. His spinal MRI T2-weighted sequence revealed an extensive hyperintense lesion involving the cervical spinal cord C(2) to C(4). Bilateral optic nerves were significantly thick. In case 3, intercurrent wheezing, tachypnea, dyspnea, and lethargy occurred from the age of 1 year. Medulla and upper cervical spine edema and demyelination were found on MRI. Markedly elevated urine organic acids and decreased blood biotinidase activities were observed in the 3 patients. Biotin supplementation led to a dramatic improvement of clinical symptoms in 3 patients. The findings indicate that biotinidase deficiency should be considered in the differential diagnosis of unexplained spinal cord demyelination because prompt diagnosis and treatment with biotin may enable an excellent recovery.
Assuntos
Deficiência de Biotinidase/complicações , Doenças Desmielinizantes/complicações , Doenças da Medula Espinal/complicações , Adolescente , Povo Asiático , Deficiência de Biotinidase/patologia , Criança , Pré-Escolar , Doenças Desmielinizantes/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Doenças da Medula Espinal/patologiaRESUMO
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.
Assuntos
Deficiência de Biotinidase/genética , Deficiência Intelectual/genética , Mutação Puntual , Espasmos Infantis/genética , Deficiência de Biotinidase/complicações , Deficiência de Biotinidase/patologia , Humanos , Lactente , Deficiência Intelectual/complicações , Deficiência Intelectual/patologia , Imageamento por Ressonância Magnética , Masculino , Espasmos Infantis/complicações , Espasmos Infantis/patologia , SíriaRESUMO
We report the case of a child with partial biotinidase deficiency and autistic developmental disorder. We arrived at the diagnosis of biotinidase deficiency when the child was almost 4 years of age. Consequently, he began cofactor biotin treatment (10 mg daily) which did not resolve his autistic behavior. His younger brother was affected by partial biotinidase deficiency diagnosed at birth through our neonatal screening program. He was precociously treated with cofactor biotin therapy (10 mg daily) and did not show any behavioral abnormality or developmental delay. Since the brain is quite vulnerable to biotin deficiency, delayed biotin therapy could result in neurological damage. Our patient is the first case of partial biotinidase deficiency associated with autism. We hypothesize that the low biotinidase activity could have caused biotin deficiency in his brain and cerebrospinal fluids and consequently serious neurological problems, such as stereotyped and autistic behaviors, which were irreversible in spite of biotin supplementation.