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Abstract: FR-PO0281

Phenotypic and Genotypic Profile of an Admixed and Ethnically Diverse Cohort of Patients with Primary Hyperoxaluria Type 1

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Heilberg, Ita Pfeferman, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
  • Vaisbich, Maria H., Universidade Federal de Sao Paulo, São Paulo, SP, Brazil

Group or Team Name

  • Primary Hyperoxaluria Brazilian Study Group.
Background

Brazil encompasses the world’s largest recently admixed population derived from distinct ancestral ethnic groups (Science, May 2025). The present study aimed to investigate phenotypic and genotypic characteristics from patients with Primary Hyperoxaluria type 1 (PH1).

Methods

A collaborative study comprising genetically confirmed cases of PH1 from distinct regions of Brazil, focusing on demographic, clinical, laboratory and genetic data was conducted.

Results

Thirty-one (31) patients, 16M/15F (24 families, 4 consanguineous). At PH1 diagnosis, CKD stage 1/2 were observed in 38.7%, CKD 3/4 in 9.7% and CKD 5 in 51.6%. Median diagnostic delay for patients of 3 groups according to their age at onset was 5.3 yrs (<2 years old , 6M/0F), 11.0 yrs (2-12 yrs, 5M/5F) and 7.0 yrs (> 12 yrs, 5M/10F). Figure 1 describes signs/symptom preceding diagnosis and Table 1 shows genetic testing results in these 3 groups. The median age of PH1 onset was 15 yrs (6.3-33.3 IQR) for patients carrying at least one c.508 G>A allele versus 4.5 yrs (0.66-18.8) for those with no c.508 G>A allele (p< 0.05).

Conclusion

These preliminary data suggested c.508 G>A as the most prevalent variant identified, (30.6% of all alleles), mainly detected in group > 12 yrs old, reflecting slower disease presentation besides progression. Present series disclosed a genetic profile similar to European and American population rates except for c.731T>C , detected in only 1 patient. Likewise, the percentage of CKD5 at PH1 diagnosis is in accordance with the literature. Ongoing research aims to validate these findings.

Genetic variant / ProteinACMG
classification
N (%)
alleles
< 2 yrs (n= 6)2-12 yrs (n=10)> 12 yrs (n=15)
HomoC. HetHomoC. HetHomoC. Het
c.508G>A / p.Gly170Arg519 (30.6)0004 (40%)5 (33.3%)5 (33.3%)
c.33dupC / p.Lys12Glnfs*15656 (9.6)01 (16.6%)03 (30%)02 (13.3%)
c.731T>C / p.Ile244Thr51 (1.6)01 (16.6%)0000
c.248G>A / p.His83Arg46 (9.6)1 (16.6%)0002 (13.3%)0
p.Ser221del55 (8.0)1 (16.6%)001(10%)02 (13.3%)
c.466G>A / p.Gly156Arg54 (6.4)1 (16.6%)1 (16.6%)01(10%)00
c.107G>A / p.Arg36His54 (6.4)01 (16.6%)03 (30%)00
c.1151T>C / p.Leu384Pro43(4.8)001(10%)001(6.7%)

Digital Object Identifier (DOI)