Fructose 1,6 bisphosphatase deficiency: outcomes of patients in a single center in Turkey and identification of novel splice site and indel mutations in
FBP1
fructose 1,6 biphosphatase
hypoglycemia
lactic acidosis
pseudohypertriglyceridemia
Journal
Journal of pediatric endocrinology & metabolism : JPEM
ISSN: 2191-0251
Titre abrégé: J Pediatr Endocrinol Metab
Pays: Germany
ID NLM: 9508900
Informations de publication
Date de publication:
26 Apr 2022
26 Apr 2022
Historique:
received:
24
09
2021
accepted:
16
01
2022
pubmed:
19
2
2022
medline:
2
4
2022
entrez:
18
2
2022
Statut:
epublish
Résumé
Fructose 1,6 bisphosphatase (FBPase) deficiency is a rare autosomal recessively inherited metabolic disease. It is encoded by In this study, we describe the clinical, biochemical, and molecular genetic features of six unrelated Turkish patients from six different families who were genetically diagnosed with FBPase deficiency in our clinic between 2008 and 2020. Their clinical and laboratory data were collected retrospectively. Next-generation sequencing (NGS) was performed for the molecular genetic analysis. All patients were hospitalized with recurrent hypoglycemia and metabolic acidosis episodes. Three out of six patients were presented in the neonatal period. The mean age at diagnosis was 26 months. NGS revealed a known homozygous gross deletion including exon 2 in three patients (50%), a known homozygous c.910_911dupTT pathogenic variant in one patient (16%), a novel homozygous c.651_653delCAGinsTAA likely pathogenic variant, and another novel homozygous c.705+5G>A splice site variant. Leukocyte FBPase analysis detected no enzyme activity in the patient with homozygous c.705+5G>A splice site variant. We identified two novel mutations in this study. One of them is a splice site mutation which is five bases downstream of the exon, and the other one is an indel mutation. Both of the splice site and indel mutations are exceedingly rare in
Identifiants
pubmed: 35179010
pii: jpem-2021-0732
doi: 10.1515/jpem-2021-0732
doi:
Substances chimiques
Fructose
30237-26-4
Fructose-Bisphosphatase
EC 3.1.3.11
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
497-503Informations de copyright
© 2022 Walter de Gruyter GmbH, Berlin/Boston.
Références
Baker, L, Winegrad, AI. Fasting hypoglycemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-bisphosphatase activity. Lancet 1970;2:13–6. https://doi.org/10.1016/s0140-6736(70)92474-8.
van den Berghe, G. Disorders of gluconeogenesis. J Inherit Metab Dis 1996;19:470–7. https://doi.org/10.1007/bf01799108.
El-Maghrabi, MR, Lange, AJ, Jiang, W, Yamagata, K, Stoffel, M, Takeda, J, et al.. Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron organization, localization to chromosome bands 9q22.2q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency. Genomics 1995;27:520–5. https://doi.org/10.1006/geno.1995.1085.
Visser, G, Bakker, HD, de Klerk, JBC, Smeitink, JAM, Smit, GPA, Wijburg, FA. Natural history and treatment of fructose-1,6, bisphosphatase deficiency in the Netherlands (abstract). J Inherit Metab Dis 2004;27(1 Suppl):207.
Lebigot, E, Brassier, A, Zater, M, Imanci, D, Feillet, F, Thérond, P, et al.. Fructose-1,6-bisphosphatase deficiency: clinical, biochemical and genetic features in French patients. J Inherit Metab Dis 2015;38:881–7. https://doi.org/10.1007/s10545-014-9804-6.
Afroze, B, Yunus, Z, Steinmann, B, Santer, R. Transient pseudo-hypertriglyceridemia: a useful biochemical marker of fructose-1,6-bisphosphatase deficiency. Eur J Pediatr 2013;172:1249–53 8. https://doi.org/10.1007/s00431-013-2084-6.
Faiyaz-Ul-Haque, M, Al-Owain, M, Al-Dayel, F, Al-Hassnan, Z, Al-Zaidan, H, Rahbeeni, Z, et al.. Novel FBP1 gene mutations in Arab patients with fructose-1,6-bisphosphatase deficiency. Eur J Pediatr 2009;168:1467–71. https://doi.org/10.1007/s00431-009-0953-9.
Steinmann, B, Santer, R. Disorders of fructose metabolism. In: Saudubray, JM, van den Berghe, G, Walter, H, editors. Inborn metabolic diseases. Heidelberg: Springer; 2012:162–5 pp.
Kılıç, M, Kasapkara, ÇS, Yılmaz, DY, Özgül, RK. Exon 2 deletion represents a common mutation in Turkish patients with fructose-1,6-bisphosphatase deficiency. Metab Brain Dis 2019;34:1487–91.
Ijaz, S, Zahoor, MY, Imran, M, Ramzan, K, Bhinder, MA, Shakeel, H, et al.. Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine consanguineous Pakistani families. J Pediatr Endocrinol Metab 2017;30:1203–10. https://doi.org/10.1515/jpem-2017-0188.
Robinson, JT, Thorvaldsdóttir, H, Winckler, W, Guttman, M, Lander, ES, Getz, G, et al.. Integrative genomics viewer. Nat Biotechnol 2011;29:24–6. https://doi.org/10.1038/nbt.1754.
Richards, S, Aziz, N, Bale, S, Bick, D, Das, S, Gastier-Foster, J, et al.. ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–24. https://doi.org/10.1038/gim.2015.30.
Santer, R, duMoulin, M, Shahinyan, T, Vater, I, Maier, E, Muntau, AC, et al.. A summary of molecular genetic findings in fructose-1,6-bisphosphatase deficiency with a focus on a common long-range deletion and the role of MLPA analysis. Orphanet J Rare Dis 2016;11:44. https://doi.org/10.1186/s13023-016-0415-1.
Herzog, B, Morris, AAM, Saunders, C, Eschrich, K. Mutation spectrum in patients with fructose-1,6-bisphosphatase deficiency. J Inherit Metab Dis 2001;24:87–8. https://doi.org/10.1023/a:1005691730058.
Baker, L, Winegrad, AI. Fasting hypoglycaemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-diphosphatase activity. Lancet 1970;2:13–6. https://doi.org/10.1016/s0140-6736(70)92474-8.
Besley, GTN, Walter, JH, Lewis, MA, Chard, CR, Addison, GM. Fructose-1,6-bisphosphatase deficiency: severe phenotype with normal leukocyte enzyme activity. J Inherit Metab Dis 1994;17:333–5. https://doi.org/10.1007/BF00711822.
KikawaY, Shin, YS, Inuzuka, M, Zammarchi, E, Mayumi, M. Diagnosis of fructose-1,6-bisphosphatase deficiency using cultured lymphocyte fraction: a secure and noninvasive alternative to liver biopsy. J Inherit Metab Dis 2002;25:41–6. https://doi.org/10.1023/a:1015129616599.
Tran, C. Inborn errors of fructose metabolism. What can we learn from them? Nutrients 2017;9:356. https://doi.org/10.3390/nu9040356.
Kikawa, Y, Inuzuka, M, Jin, BY, Kaji, S, Yamamoto, Y, Shigematsu, Y, et al.. Identification of a genetic mutation in a family with fructose-1,6-bisphosphatase deficiency. Biochem Biophys Res Commun 1995;210:797–804. https://doi.org/10.1006/bbrc.1995.1729.
Desmet, FO, Hamroun, D, Lalande, M, Collod-Béroud, G, Claustres, M, Béroud, C. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 2009;37:e67. https://doi.org/10.1093/nar/gkp215.
Lebigot, E, Brassier, A, Zater, M, Imanci, D, Feillet, F, Thérond, P, et al.. Boutron A Fructose 1,6-bisphosphatase deficiency: clinical, biochemical and genetic features in French patients. J Inherit Metab Dis 2015;38:881–7. https://doi.org/10.1007/s10545-014-9804-6.
Bulut, D, Seker-Yilmaz, B, Kor, D, Ceylaner, S, Ozgur-Horoz, O, Onenli-Mungan, N. Fructose-1,6-bisphosphatase deficiency in early childhood: 5 Turkish cases (abstract). J Inherit Metab Dis 2015;38(1 Suppl):179.