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Journal of Pediatric Genetics Mar 2023Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When... (Review)
Review
Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the gene are reported worldwide. Mutations in the gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.
PubMed: 36684547
DOI: 10.1055/s-0042-1757887 -
Molecular Genetics and Metabolism Dec 2022Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common "mimics" of cerebral... (Review)
Review
Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common "mimics" of cerebral palsy. Early detection of these heterogenous genetic disorders can inform genetic counseling, anticipatory guidance, and improve outcomes, particularly where specific treatments exist. The diagnosis relies on clinical pattern recognition, biochemical testing, neuroimaging, and increasingly next-generation sequencing-based molecular testing. In this short review, we summarize the clinical and molecular understanding of: 1) childhood-onset and complex forms of hereditary spastic paraplegia (SPG5, SPG7, SPG11, SPG15, SPG35, SPG47, SPG48, SPG50, SPG51, SPG52) and, 2) the most common inborn errors of metabolism that present with phenotypes that resemble hereditary spastic paraplegia.
Topics: Child; Humans; Spastic Paraplegia, Hereditary; Phenotype; Retinal Degeneration; High-Throughput Nucleotide Sequencing; Metabolism, Inborn Errors; Mutation; Proteins
PubMed: 34183250
DOI: 10.1016/j.ymgme.2021.06.006 -
Annals of Indian Academy of Neurology 2020Movement disorders in childhood comprise a heterogeneous group of conditions that lead to impairment of voluntary movement, abnormal postures, or inserted involuntary...
Movement disorders in childhood comprise a heterogeneous group of conditions that lead to impairment of voluntary movement, abnormal postures, or inserted involuntary movements. Movement disorders in children are frequently caused by metabolic disorders, both inherited and acquired. Many of these respond to vitamin supplementation. Examples include infantile tremor syndrome, biotinidase deficiency, biotin-thiamine-responsive basal ganglia disease, pyruvate dehydrogenase deficiency, aromatic amino acid decarboxylase deficiency, ataxia with vitamin E deficiency, abetalipoproteinemia, cerebral folate deficiency, and cobalamin metabolism defects. Recognition of these disorders by pediatricians and neurologists is imperative as they are easily treated by vitamin supplementation. In this review, we discuss vitamin-responsive movement disorders in children.
PubMed: 32606520
DOI: 10.4103/aian.AIAN_678_19 -
Journal of Pediatric Neurosciences 2018This review offers an update on a group of inborn errors of metabolism causing severe epilepsy with the onset in pediatric age (but also other neurological... (Review)
Review
This review offers an update on a group of inborn errors of metabolism causing severe epilepsy with the onset in pediatric age (but also other neurological manifestations such as developmental delay or movement disorders) with available effective or potentially effective treatments. The main pathogenic and clinical features and general recommendations for the diagnostic and therapeutic workup of the following disorders are discussed: vitamin B-dependent epilepsies, cerebral folate deficiency, congenital disorders of serine metabolism, biotinidase deficiency, inborn errors of creatine metabolism, molybdenum cofactor deficiency, and glucose transporter 1 deficiency. Available treatments are more effective on epileptic manifestations (with the possibility of complete seizure control) and motor symptoms, whereas the benefits on cognitive outcome are usually minor.
PubMed: 29899766
DOI: 10.4103/JPN.JPN_160_16 -
Journal of Pediatric Endocrinology &... Aug 2018Background Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling. It is classified into two levels based on the biotinidase... (Clinical Trial)
Clinical Trial
Background Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling. It is classified into two levels based on the biotinidase enzyme activity: partial deficiency (10%-30% enzyme activity) and profound deficiency (0%-10% enzyme activity). The aims of this study were to evaluate our patients with BD, identify the spectrum of biotinidase (BTD) gene mutations in Turkish patients and to determine the clinical and laboratory findings of our patients and their follow-up period. Methods A total of 259 patients who were diagnosed with BD were enrolled in the study. One hundred and forty-eight patients were male (57.1%), and 111 patients were female (42.9%). Results The number of patients detected by newborn screening was 221 (85.3%). By family screening, 31 (12%) patients were diagnosed with BD. Seven patients (2.7%) had different initial complaints and were diagnosed with BD. Partial BD was detected in 186 (71.8%) patients, and the profound deficiency was detected in 73 (28.2%) patients. Most of our patients were asymptomatic. The most commonly found variants were p.D444H, p.R157H, c.98_104delinsTCC. The novel mutations which were detected in this study are p.D401N(c.1201G>A), p.A82G (c.245C>G), p.F128S(c.383T>C), c617_619del/TTG (p.Val207del), p.A287T(c.859G>A), p.S491H(c.1471A>G). The most common mutation was p.R157H in profound BD and p.D444H in partial BD. All diagnosed patients were treated with biotin. Conclusions The diagnosis of BD should be based on plasma biotinidase activity and molecular analysis. We determined the clinical and genetic spectra of a large group of patients with BD from Western Turkey. The frequent mutations in our study were similar to the literature. In this study, six novel mutations were described.
Topics: Adolescent; Adult; Biotinidase; Biotinidase Deficiency; Child; Child, Preschool; Family; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Mutation; Neonatal Screening; Prognosis; Turkey; Young Adult
PubMed: 29995633
DOI: 10.1515/jpem-2018-0148 -
The Turkish Journal of Pediatrics 2022Phenylketonuria (PKU) and biotinidase deficiency (BD) are autosomal recessive diseases. If they are not identified and treated early, severe intellectual disability and...
BACKGROUND
Phenylketonuria (PKU) and biotinidase deficiency (BD) are autosomal recessive diseases. If they are not identified and treated early, severe intellectual disability and developmental delay occur. This study was conducted to calculate the ten-year incidence of PKU and BD in the Diyarbakır province of Turkey.
METHODS
This cross-sectional study included patients born between 2011-2020 and diagnosed with PKU and BD. Patients with a clear diagnosis had their records evaluated retrospectively.
RESULTS
Between 2011 and 2020, blood was taken from 417,525 newborns` heels in Diyarbakir province. As a result of further diagnostic testing, 53 PKU (Incidence: 1:7878) and 177 BD (Incidence: 1:2359) were detected. Of the patients with BD, 56% had profound BD and 44% had partial BD. The records of a total of 269 patients (PKU: 25; BD: 123; Hyperphenylalaninemia: 121) were examined. Parents of 65% (n=15) of the patients diagnosed with PKU and 46.6% (n=55) of the patients diagnosed with BD were consanguineous.
CONCLUSIONS
The incidence of both PKU and BD was found to be high in our region. The high number of consanguineous marriages was regarded as the most important explanation for the high frequency of these illnesses.
Topics: Humans; Infant, Newborn; Neonatal Screening; Biotinidase Deficiency; Retrospective Studies; Cross-Sectional Studies; Phenylketonurias
PubMed: 36583880
DOI: 10.24953/turkjped.2022.467 -
Genes Apr 2022Biotinidase deficiency (BD) is a rare autosomal recessive metabolic disease. Previously the disease was identified only by clinical signs and symptoms, and since...
Biotinidase deficiency (BD) is a rare autosomal recessive metabolic disease. Previously the disease was identified only by clinical signs and symptoms, and since recently, it has been included in newborn screening programs (NBS) worldwide, though not commonly. In Europe, BD prevalence varies highly among different countries, e.g., from 1:7 116 in Turkey to 1:75 842 in Switzerland. This paper aimed to present the molecular spectrum of BD (profound and partial forms) in Polish patients diagnosed within the national NBS of 1,071,463 newborns. The initial suspicion of BD was based on an abnormal biotinidase activity result determined in a dry blood spot (DBS) by colorimetric and by fluorimetric methods while biochemical verification was determined by serum biotinidase activity (as quantitative analysis). The final diagnosis of BD was established by serum enzyme activity and the gene direct sequencing. The obtained results allowed for the estimation of disease prevalence (1:66,966 births, while 1:178,577 for profound and 1:107,146 for partial forms), and gave novel data on the molecular etiology of BD.
Topics: Biotinidase; Biotinidase Deficiency; Humans; Infant, Newborn; Mutation; Neonatal Screening; Poland; Prevalence
PubMed: 35627187
DOI: 10.3390/genes13050802 -
Annals of Indian Academy of Neurology 2020
PubMed: 33688141
DOI: 10.4103/aian.AIAN_503_19 -
Journal of Audiology & Otology Apr 2016Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia....
Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency.
PubMed: 27144235
DOI: 10.7874/jao.2016.20.1.53 -
BMC Medical Genetics Sep 2014Biotinidase deficiency (BD) is an inborn error of metabolism in which some genetic variants correlate with the level of enzyme activity. Biotinidase activity, however,... (Observational Study)
Observational Study
BACKGROUND
Biotinidase deficiency (BD) is an inborn error of metabolism in which some genetic variants correlate with the level of enzyme activity. Biotinidase activity, however, may be artifactually low due to enzyme lability, premature birth, and jaundice; this hinders both phenotypic classification and the decision to implement therapy. This study sought to characterize the clinical and genetic profile of a sample of Brazilian patients exhibiting reduced biotinidase activity.
METHODS
This observational, multicenter study used a convenience sampling strategy, with sequencing of exons 2, 3, and 4 of the BTD gene.
RESULTS
The sample comprised 38 individuals with biochemical phenotypes defined a priori on the basis of biotinidase activity in serum/plasma (2 with profound deficiency, 9 with partial deficiency, 15 heterozygous, 1 borderline between partial deficiency and heterozygosity, 2 borderline between heterozygous and normal) or dried blood spot sample (n = 9, all with unspecified deficiency). Most patients were from Southern Brazil (n = 29/38) and were identified by neonatal screening (n = 33/38). Parental consanguinity was reported in two cases. The most commonly found genetic variants were c.1330G > C (p.D444H), c.755A > G (p.D252G), and c.[511G > A;1330G > C] (p.[A171T;D444H]), with allele frequencies of 50%, 9.4%, and 5.4% respectively. Three novel pathogenic variants were identified (c.119 T > C or p.L40P, c.479G > A or p.C160Y, and c.664G > A or p.D222N). Twenty-nine patients had two pathogenic variants detected (with cis/trans status ascertained in 26/29), six had only one variant, and three had no pathogenic variants detected. Genotyping confirmed the original phenotypic classification based on enzyme activity in 16/26 cases. Three polymorphic variants were identified in control individuals, of which two were nonpathogenic (c.1171C > T or p.P391S and c.1413 T > C or p.C471C, with a frequency of 1.5% and 5.5% respectively) and one pathogenic (c.1330G > C, frequency 4%).
CONCLUSIONS
Our findings suggest that partial BD is the most common form of BD in Brazil, and expand current knowledge on the allelic heterogeneity of this condition.
Topics: Biotinidase; Biotinidase Deficiency; Brazil; Cross-Sectional Studies; Exons; Female; Genetic Heterogeneity; Genetic Variation; Humans; Infant, Newborn; Male; Neonatal Screening; Polymorphism, Single Nucleotide
PubMed: 25174816
DOI: 10.1186/s12881-014-0096-3