Acute renal failure in a 7-year-old boy: do not miss rare and treatable cause

Boussetta, Abir; Jellouli, Manel; Maamouri, Rym; Talbi, Arbia; Skhiri, H.; Gargah, Tahar

doi:10.1007/s40620-021-01190-z

Cited by 1 publication

(1 citation statement)

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“…It is crucial to identify these non-complement-mediated disorders because complement-based therapies are generally inefficient in these patients [1, 6]. However, co-occurrence of variants in complement genes and MMACHC or genes encoding coagulation factors has been reported, and complement blockade may also be favorable in such rare circumstances [1, 7].…”

Section: Discussionmentioning

confidence: 99%

Concurrent Cobalamin C and Plasminogen Deficiencies in a Patient with Chronic Thrombotic Microangiopathy

Dirim,

Safak,

Balci

et al. 2023

Nephron

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Background: Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG, and THBD, have also been described. Case Presentation: We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHC c.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG (p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLG and MMACHC variants. PLG variants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLG variants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. Conclusion: Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.

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