Renotubular Fanconi syndrome type 1 in children: a case series

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Renal Fanconi syndrome is a generalized disorder of the proximal convoluted tubule, characterized by non-selective aminoaciduria, glucosuria, low molecular weight proteinuria, phosphaturia, loss of bicarbonates, electrolytes and many other substances. Autosomal dominant Fanconi renotubular syndromes due to a GATM missense-variant, encodes mitochondrial enzyme arginine-glycine amidinotransferase. In total, 36 cases of genetically confirmed Fanconi renotubular syndrome, type 1 have been reported to date from 10 families. In this article, we present the first Russian cases of two unrelated patients with previously undescribed variants c.1076C>T (p.Ser359Phe) and c.1079T>A (p.Met360Lys) in the GATM gene. The first clinical features of the disease with complete Fanconi syndrome were diagnosed in both cases in early childhood. A decrease of renal function was detected in each of cases already during the first examinations, but the rate of progression was different. The patient 1 had a rate of eGFR decline of 0.6 ml/min/1.73 m2 per year, whereas patient 2 demonstrated a higher rate of eGFR decline (-2.1 ml/min/1.73 m2/year). Symptomatic therapy resulted in normalization of growth rates and a decrease in the activity of rickets in patient 1. In patient 2, despite the therapy, signs of osteomalacia persisted, and rachitic deformities of the limbs required orthopedic correction.

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Svetlana Papizh

Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University (Pirogov University)

编辑信件的主要联系方式.
Email: papijsveta@mail.ru
ORCID iD: 0000-0001-6459-2795

Cand. Sci. (Med.)

 

俄罗斯联邦, Moscow

Anastasiia Topchii

Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University (Pirogov University)

Email: papijsveta@mail.ru
ORCID iD: 0009-0001-3993-8472

Graduate Student

俄罗斯联邦, Moscow

Tatiana Nikishina

Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University (Pirogov University)

Email: papijsveta@mail.ru
ORCID iD: 0009-0000-8590-6140

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

参考

  1. Klootwijk ED, Reichold M, Unwin RJ, et al. Renal Fanconi syndrome: taking a proximal look at the nephron. Nephrol Dial Transplant. 2015;30:1456-60.
  2. Reichold M, Klootwijk ED, Reinders J, et al. Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure. J Am Soc Nephrol. 2018;29(7):1849-58.
  3. Ragate DC, Memon SS, Karlekar M, et al. Inherited Fanconi renotubular syndromes: unveiling the intricacies of hypophosphatemic rickets/osteomalacia. J Bone Miner Metab. 2024;42(2):155-65.
  4. Li CY, Sun Y, Guo WC, et al. Complex phenotype in Fanconi renotubular syndrome type 1: Hypophosphatemic rickets as the predominant presentation. Clin Chim Acta. 2024;561:119812.
  5. Seaby EG, Turner S, Bunyan DJ, et al. A novel variant in GATM causes idiopathic renal Fanconi syndrome and predicts progression to end-stage kidney disease. Clin Genet. 2023;103(2):214-8.
  6. Kudo H, Suzuki R, Kondo A, et al. Association of familial Fanconi syndrome with a novel GATM variant. Tohoku J Exp Med. 2023;260(4):337-40.
  7. Koyun M, Ertosun MG, Aksoy GK, et al. An uncommon cause of hypophosphatemic rickets: answers. Pediatr Nephrol. 2023;38(8):2613-4.
  8. Item CB, Stöckler-Ipsiroglu S, Stromberger C, et al. Arginine: glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001;69(5):1127-33.
  9. Portales-Castillo I, Singal R, Ambrose A, et al. Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L GATM variant and study of organoids towards treatment. JIMD Reports. 2024;1-13.
  10. Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857-65.
  11. Dostert C, Pétrilli V, Van Bruggen R, et al. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science. 2008;320:674-7.
  12. Liu B, Gao X, Teng H, et al. Association between GATM gene polymorphism and progression of chronic kidney disease: a mitochondrial related genome-wide Mendelian randomization study. Sci Rep. 2024;14:20346.
  13. Nouioua S, Cheillan D, Zaouidi S, et al. Creatine deficiency syndrome. A treatable myopathy due to arginine–glycine amidinotransferase (AGAT) deficiency. Neuromuscul Disord. 2013;23(8):670-4.
  14. Verma A. Arginine: glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy. Neurology. 2010;75(2):186-8.
  15. Verhoeven NM, Schor DS, Roos B, et al. Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect L-arginine: glycine amidinotransferase deficiency. Clin Chem. 2003;49(5):803-5.
  16. Takasato M, Er PX, Chiu HS, Little MH. Generation of kidney organoids from human pluripotent stem cells. Nat Protoc. 2016;11(9):1681-92

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1. JATS XML
2. Fig. 1. Calcifications in the renal medulla in the patient 1.

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3. Fig. 2. Medullary nephrocalcinosis, grade 2 in case 2.

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