The First Case of Lipoprotein Glomerulopathy in a Patient With Male Infertility

May combine two claims.

ApoE/LDL receptor-deficient mice exhibit testicular microvascular damage and reduced serum testosterone, leading to infertility.

“These deficient mice exhibited testicular microvascular damage and reduced serum testosterone levels, ultimately leading to mice infertility.17”

• cites [17] Steinfeld, 2018, Low testosterone in ApoE/LDL receptor double-knockout mice is associated with rarefied testicular capillaries together with fewer and smaller Leydig cells, Sci Rep sourcePartly supported

  The Discussion reports testicular capillary rarefaction and reduced serum testosterone in ApoE/LDL receptor double-knockout mice. The Abstract says reduced litter size suggests hypo- or infertility as a consequence of testicular defects, but the claim states infertility as a definite outcome. The Discussion also says female fertility disturbances cannot be excluded as a contributor to reduced litter size. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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APOE gene mutation leads to elevated serum apolipoprotein E (ApoE) levels and glomerular capillary occlusion by massive lipoprotein thrombi composed of ApoB and ApoE, causing glomerular damage and renal impairment.

“APOE gene mutation leads to elevated serum apolipoprotein E (ApoE) levels, and glomerular capillary lumens become occluded by massive lipoprotein thrombi composed of ApoB and ApoE, thereby resulting in glomerular damage and renal impairment.1, 2, 3”

• cites [1] Saito, 2020, Apolipoprotein E-related glomerular disorders, Kidney Int sourceNot checked — no full text of the source
• cites [2] Khalil, 2021, APOE gene variants in primary dyslipidemia, Atherosclerosis sourceNot checked — no full text of the source
• cites [3] Song, 2021, Case Report: A pediatric case of lipoprotein glomerulopathy in China and literature review, Front Pediatr sourcePartly supported

  The Introduction describes massive lipoprotein thrombi in dilated glomerular capillaries and renal disease; the Discussion reports increased serum apoE in patients with lipoprotein glomerulopathy. But the paper does not establish that an APOE mutation invariably causes the full sequence claimed: its Discussion says mutations are not necessary for the disease and its mechanisms remain unclear. The passages also do not identify the thrombi as composed of ApoB and ApoE. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

An APOE frameshift mutation was identified in testicular biopsies from patients with nonobstructive azoospermia.

“Meanwhile, Cheung et al5 reported the identification of an APOE frameshift mutation in testicular biopsies from patients with nonobstructive azoospermia.5”

• cites [5] Cheung, 2024, Genetic profiling of azoospermic men to identify the etiology and predict reproductive potential, J Assist Reprod Genet sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Total cholesterol levels vary significantly across different APOE genotypes, with the difference more pronounced in young individuals.

“a study explored the effect of APOE gene polymorphism on reproductive potential and found that the total cholesterol levels varied significantly across different APOE genotypes. The difference was more pronounced in young individuals”

• cites [16] Corbo, 2004, Differential reproductive efficiency associated with common apolipoprotein E alleles in postreproductive-aged subjects, Fertil Steril sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Secretion of ApoB depends on binding of ApoE to LDL receptors.

“It has been reported that the secretion of ApoB depends on the binding of ApoE to LDL receptors.12”

• cites [12] Blasiole, 2008, Regulation of ApoB secretion by the low density lipoprotein receptor requires exit from the endoplasmic reticulum and interaction with ApoE or ApoB, J Biol Chem sourcePartly supported

  The Discussion (page not available in our copy) identifies apoE as a ligand through which LDL receptors regulate apoB secretion. But it says that this interaction reduces secretion, not that apoB secretion generally depends on it; the paper also describes LDL-receptor binding through apoB as an alternative. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Male infertility is associated with variations in APOE genotypes.

“Beyond LPG, recently the increased studies have showed that male infertility is associated with variations in APOE genotypes.4,5”

• cites [4] Setarehbadi, 2012, Apolipoprotein E genotypes of fertile and infertile men, Syst Biol Reprod Med sourceSupported
• cites [5] Cheung, 2024, Genetic profiling of azoospermic men to identify the etiology and predict reproductive potential, J Assist Reprod Genet sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The presence of the ε3ε4 genotype is associated with a 3.82-fold increased risk of male infertility.

“Specifically, the presence of the ε3ε4 genotype was associated with a 3.82-fold increased risk of male infertility.4”

• cites [4] Setarehbadi, 2012, Apolipoprotein E genotypes of fertile and infertile men, Syst Biol Reprod Med sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

There is a clear inverse relationship between number of children and ε2-carrying genotype proportions.

“that there was a clear inverse relationship between number of children and ε2-carrying genotype proportions.”

• cites [16] Corbo, 2004, Differential reproductive efficiency associated with common apolipoprotein E alleles in postreproductive-aged subjects, Fertil Steril sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

There is a significant difference in the distribution of APOE genotypes between fertile and infertile males.

“A previous experiment explored the correlation between APOE genotype (ε3ε3, ε3ε4 and ε2ε3) and male infertility, which found that there was a significant difference in the distribution of APOE genotypes between fertile and infertile males.”

• cites [4] Setarehbadi, 2012, Apolipoprotein E genotypes of fertile and infertile men, Syst Biol Reprod Med sourceSupported

May combine two claims.

Lipoprotein glomerulopathy (LPG) is a rare hereditary glomerular disease characterized by lipoprotein thrombi deposition in glomerular capillaries and caused by pathogenic variants in the APOE gene.

“Lipoprotein glomerulopathy (LPG) is a rare hereditary glomerular disease with lipoprotein thrombi deposition in glomerular capillaries, which is caused by pathogenic variants in APOE gene.”

• Also stated in: § Abstract · plain

  “Lipoprotein glomerulopathy (LPG) is considered a rare hereditary glomerular disorder, with APOE gene mutation recognized as the primary pathogenic factor.”

• cites [1] Saito, 2020, Apolipoprotein E-related glomerular disorders, Kidney Int sourceNot checked — no full text of the source
• cites [2] Khalil, 2021, APOE gene variants in primary dyslipidemia, Atherosclerosis sourceNot checked — no full text of the source
• cites [3] Song, 2021, Case Report: A pediatric case of lipoprotein glomerulopathy in China and literature review, Front Pediatr sourcePartly supported

  The Introduction describes LPG as a rare hereditary renal disorder and identifies lipoprotein thrombi in glomerular capillaries as its key histopathologic feature. The Discussion links APOE mutations to LPG but also reports cases without mutations and explicitly says an APOE mutation is not necessary for LPG to develop. Thus, the claim overstates APOE variants as a universal cause. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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Mutated APOE is necessary but not the only determinant in the development of LPG.

“Mutated APOE is necessary but not the only determinant in the development of LPG.”

• cites [9] Cambruzzi, 2019, Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: a review, J Bras Nefrol sourcePartly supported

  The Pathogenesis section says that family findings favor the hypothesis that abnormal ApoE is necessary but not the only determinant of LPG. The claim presents necessity as established and specifies mutated ApoE, whereas the same passage reports LPG patients in whom no ApoE gene mutation was found. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims. The quote only partly states this claim.

The patient had nephrotic syndrome with proteinuria 2+ and serum albumin 24.8 g/L.

“Based on proteinuria (2+) and hypoproteinemia (serum albumin level, 24.8 g/L), he was suspected of nephrotic syndrome.”

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The patient had a heterozygous APOE mutation c.127C>T (p.Arg43Cys) in exon 3, inherited from his mother.

“sequencing detection revealed a heterozygous mutation that in exon 3 the nucleotide 127 of APOE gene encoding region was mutated from cytosine to thymine (c.127C>T), which resulted in a missense mutation of amino acid 43 from arginine to cysteine (p.Arg43Cys)”

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Semen analysis showed total and progressive motility below WHO 2021 reference limits.

“Semen analysis was taken several times, and results showed that both total and progressive motility were below WHO 2021 reference limits.”

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After four months of treatment, the patient's wife conceived naturally and gave birth to a full-term infant.

“Furthermore, after four months’ treatment the patient’s wife conceived naturally and ultimately gave birth to a full-term infant.”

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The patient was a 36-year-old slim man who presented with nephrotic syndrome and abnormal sperm quality.

“Herein, we report a 36-year-old slim man who presented with nephrotic syndrome and had abnormal sperm quality.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The patient had high blood pressure of about 173/115 mmHg and a body mass index of 21.97 kg/m2.

“his blood pressure was specifically high about 173/115 mmHg and body mass index was 21.97 kg/m2.”

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Electron microscopy showed massive lipoprotein thrombi occupying glomerular capillary lumens and widely fused podocyte foot processes.

“electron microscopy also showed massive lipoprotein thrombi occupied glomerular capillary lumens. Simultaneously, the foot processes of podocytes were widely fused”

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The APOE mutation is likely pathogenic and inherited from the patient's mother.

“It is a likely pathogenic mutation inherited from his mother”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The patient's elder sister was diagnosed with IgA nephropathy 12 years ago and lupus nephritis 9 years later.

“the patient’s elder sister was explicitly diagnosed with IgA nephropathy 12 years ago and then 9 years later confirmed with lupus nephritis.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The patient desired fertility but had no baby for 4 years after marriage.

“as a young man he desired for fertility but without a baby for 4 years after marriage.”

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The patient's male infertility was reversed after treatment, as indicated by natural conception.

“At the subsequent follow-up, male infertility in this patient was unexpectedly reversed, as implicitly indicated by the spouse’s naturally conception in July 2024 and finally delivery of a full-term infant in February 2025 (Table 2).”

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Lack of paternal genetic data precludes establishment of a complete familial genetic transmission chain and prevents fully excluding patrilineal inheritance impact.

“In this case, the lack of paternal genetic data precludes the establishment of a complete familial genetic transmission chain. This prevents us from fully excluding the potential impact of patrilineal inheritance on our findings and thus hinders the accurate determination of the transmission patterns of pathogenic genes.”

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In patients with this mutation, excess lipids deposit in the kidney rather than participate in circulatory metabolism or form adipose tissue, which may explain their thin appearance.

“In fact, the excess lipids in these patients deposit in the kidney rather than participate in circulatory metabolism or form adipose tissue. This phenomenon may elucidate why these patients present with a thin appearance.”

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Inability to obtain maternal relatives precluded further genetic analysis and phenotypic documentation, potentially underestimating pathogenic mutation carriers and failing to identify incomplete penetrance.

“the inability to obtain samples from maternal relatives has precluded further genetic analysis and phenotypic documentation. This may lead to an underestimation of the number of pathogenic mutation carriers and a failure to accurately identify individuals with incomplete penetrance”