scholarly journals Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

2021 ◽  
Vol 9 ◽  
Author(s):  
Alice Maguolo ◽  
Giulia Rodella ◽  
Alice Dianin ◽  
Irene Monge ◽  
Martina Messina ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Neonatal Intensive Care ◽  
Autosomal Recessive ◽  
Biotinidase Deficiency ◽  
Phenotype Correlation ◽  
Regional Center ◽  
Asymptomatic Patients ◽  
Total Incidence ◽  
Disease Unit

Introduction: Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients.Methods: We analyzed data of patients identified by the Regional Centre for Newborn Screening of Verona and followed by the Inherited Metabolic Disease Unit of Verona and Neonatal Intensive Care Unit of Bolzano, Italy, from 2014 to 2020.Results: Thirty-seven patients were diagnosed by NBS (five profound and 32 partial BD), with a total incidence of 1:5,996. All were started on biotin at diagnosis and presented no symptoms at follow-up. Analysis of parents and siblings led to identification of five asymptomatic patients with partial BD: one asymptomatic parent and four young siblings. Genetic analysis of the BTD gene identified 17 different genotypes and one mutation not previously known.Discussion: Our data confirm that NBS introduction had a dramatic impact on BD diagnosis, and the incidence has increased significantly compared to other areas. Partial defects are more common than profound and have a distinctive genotype. Partial BD treatment is still controversial even at what dose of biotin and for how long. At the end, BD treatment is very easy and inexpensive and prevents severe neurological damage. Sharing experiences is essential to achieving guidelines for treatment and follow-up and a better genotype–phenotype correlation.

Clinical and molecular characteristics and time of diagnosis of patients with classical galactosemia in an unscreened population in Turkey

2019 ◽  
Vol 32 (7) ◽  
pp. 675-681
Author(s):  
Pelin Teke Kisa ◽  
Melis Kose ◽  
Ozlem Unal ◽  
Esra Er ◽  
Burcu Ozturk Hismi ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Autosomal Recessive ◽  
Screening Program ◽  
Clinical Manifestations ◽  
Geographical Location ◽  
Molecular Characteristics ◽  
Phenotype Correlation ◽  
Classical Galactosemia ◽  
Pathogenic Variants ◽  
Turkish Patients

Abstract Classical galactosemia is an autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in the GALT gene. With the benefit of early diagnosis by newborn screening, the acute presentation of galactosemia can be prevented. In this study, we describe the clinical phenotypes, time of diagnosis and GALT genotypes of 76 galactosemia patients from Turkey, where the disease is not yet included in the newborn screening program. The median age at first symptom was 10 days (range 5–20), while the median age at diagnosis was 30 days (range 17–53). Nearly half of the patients (36 patients, 47.4%) were diagnosed later than age 1 month. Fifty-eight individuals were found to have 18 different pathogenic variants in their 116 mutant alleles. In our sample, Q188R variant has the highest frequency with 53%, the other half of the allele frequency of the patients showed 17 different genotypes. Despite presenting with typical clinical manifestations, classical galactosemia patients are diagnosed late in Turkey. Due to the geographical location of our country, different pathogenic GALT variants may be seen in Turkish patients. In the present study, a clear genotype-phenotype correlation could not be established in patients.

scholarly journals Clinical, biochemical, and molecular spectrum of short/branched-chain acyl-CoA dehydrogenase deficiency: two new cases and review of literature

2019 ◽  
Vol 32 (2) ◽  
pp. 101-108 ◽  
Author(s):  
Francesco Porta ◽  
Nicoletta Chiesa ◽  
Diego Martinelli ◽  
Marco Spada
Keyword(s):  
Urinary Excretion ◽  
Newborn Screening ◽  
Developmental Delay ◽  
Failure To Thrive ◽  
Pivalic Acid ◽  
Metabolic Decompensation ◽  
Asymptomatic Patients ◽  
Chain Acyl ◽  
Branched Chain

Abstract Background Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency is a rare inborn error of metabolism with uncertain clinical significance. As it leads to C5-carnitine (i.e. isovalerylcarnitine, 2methylbutyrilcarnitine, or pivaloylcarnitine) elevation, SBCAD deficiency is detectable at newborn screening, requiring differential diagnosis from isovaleric acidemia and pivalic acid administration. Increased urinary excretion of 2-methylbutyrylglycine (2MBG) is the hallmark of SBCAD deficiency. Methods We report two cases of SBCAD deficiency and provide a review of the available literature on this condition. Results Two siblings newly diagnosed with SBCAD deficiency are reported. Newborn screening allowed the early diagnosis in the second-born (C5=0.5 μmol/L, normal 0.05–0.3 μmol/L) and addressed selective screening in the 5-year asymptomatic brother (C5=1.9 μmol/L). Both patients showed increased urinary excretion of 2MBG and two mutations in the ACADSB gene (c.443C>T/c.1145C>T). Currently, both the patients are asymptomatic. Longitudinal biochemical monitoring of the two patients while on treatment with carnitine (100 mg/kg/day) was provided. Based on our experience and the literature review (162 patients), SBCAD deficiency is symptomatic in about 10% of reported patients. Clinical onset occurs in newborns or later in life with seizures, developmental delay, hypotonia, and failure to thrive. On longitudinal follow-up, epilepsy, developmental delay, microcephaly, and autism can develop. Acute metabolic decompensation due to catabolic stressors can occur, as observed in one newly reported patient. Fifteen mutations in the ACADSB gene are known, including the newly identified variant c.1145C>T (p.Thr382Met), variably associated to the phenotype. In the Hmong population, SBCAD deficiency is highly prevalent, mostly due to the founder mutation c.1165A>G, and is largely asymptomatic. Conclusions Although mostly asymptomatic, considering SBCAD deficiency as a non-disease in non-Hmong subjects appears unsafe. Catabolic situations can precipitate acute metabolic decompensation. Carnitine supplementation and valproate avoidance appear to be indicated. Providing an emergency protocol for the management of acute catabolic episodes seems reasonable in asymptomatic patients with SBCAD deficiency. Longitudinal follow-up is recommended.

Newborn screening for biotinidase deficiency: pilot study and follow-up of identified cases

Screening ◽  
1992 ◽  
Vol 1 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Michael G. Lawler ◽  
Deborah L. Frederick ◽  
Susana Rodriguez-Anza ◽  
Barry Wolf ◽  
Harvey L. Levy
Keyword(s):  
Pilot Study ◽  
Newborn Screening ◽  
Biotinidase Deficiency

scholarly journals Current status of newborn screening for Pompe disease in Japan

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Takaaki Sawada ◽  
Jun Kido ◽  
Keishin Sugawara ◽  
Ken Momosaki ◽  
Shinichiro Yoshida ◽  
...  
Keyword(s):  
United States ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Autosomal Recessive ◽  
Late Onset ◽  
The United States ◽  
Current Status ◽  
Inherited Metabolic Disorder ◽  
Enzyme Replacement

Abstract Background Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (GAA). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease. Results From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years. Conclusions The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.

scholarly journals Current Status of Newborn Screening for Pompe Disease in Japan

2021 ◽  
Author(s):  
Takaaki Sawada ◽  
Jun Kido ◽  
Keishin Sugawara ◽  
Ken Momosaki ◽  
Shinichiro Yoshida ◽  
...  
Keyword(s):  
United States ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Autosomal Recessive ◽  
Late Onset ◽  
The United States ◽  
Current Status ◽  
Inherited Metabolic Disorder ◽  
Enzyme Replacement

Abstract Background: Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (AαGlu). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease.Results: From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years.Conclusions: The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.

Cognitive function in early treated biotinidase deficiency: Follow-up of children detected by newborn screening

Screening ◽  
1995 ◽  
Vol 4 (3) ◽  
pp. 125-130 ◽  
Author(s):  
Jody Warner-Rogers ◽  
Susan E. Waisbren ◽  
Harvey L. Levy
Keyword(s):  
Cognitive Function ◽  
Newborn Screening ◽  
Biotinidase Deficiency

scholarly journals Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey

2018 ◽  
Vol 31 (3) ◽  
pp. 339-343 ◽  
Author(s):  
Berna Seker Yilmaz ◽  
Neslihan Onenli Mungan ◽  
Deniz Kor ◽  
Derya Bulut ◽  
Gülşah Seydaoglu ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Autosomal Recessive ◽  
Biotinidase Deficiency ◽  
Genetic Profile ◽  
Homozygous Mutation ◽  
The Novel ◽  
Southeastern Part ◽  
Pathogenic Variants ◽  
Mutation Spectra ◽  
Biotinidase Activity

Abstract Background: Biotinidase deficiency (BD) is an autosomal recessive inborn error of metabolism characterized by neurologic and cutaneous symptoms and can be detected by newborn screening. Newborn screening for BD was implemented in Turkey at the end of 2008. Methods: In total, 203 patients who were identified among the infants detected by the newborn screening were later confirmed to have BD through measurement of serum biotinidase activity. We also performed BTD mutation analysis to characterize the genetic profile. Results: Twenty-seven mutations were identified. The most commonly found variants were c.1330G>C (p.D444H), c.1595C>T (p.T532M), c.470G>A (p.R157H), and c.198_104delGCGGCTGinsTCC (p.C33Ffs ) with allele frequencies of 0.387, 0.175, 0.165 and 0.049, respectively. Three novel pathogenic and likely pathogenic variants were identified: p.W140* (c.419G>A), p.S319F (c.956C>T) and p.L69Hfs*24 (c.192_193insCATC). We also identified three mutations reported in just one patient in the past (p.V442Sfs*59 [c.1324delG], p.H447R [c.1340A>G] and p.198delV [c.592_594delGTC]). Although all of the patients were asymptomatic under the treatment of biotin, only one patient, who had the novel c.419G>A homozygous mutation became symptomatic during an episode of acute gastroenteritis with a presentation of ketosis and metabolic acidosis. Among the screened patients, 156 had partial and 47 had profound BD. Conclusions: We determined the mutation spectra of BD from the southeastern part of Turkey. The results of this study add three more mutations to the total number of mutations described as causing BD.

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