Atypical hemolytic uremic syndrome induced by CblC subtype of methylmalonic academia: A case report and literature review

Abstract

Rationale: Methylmalonic acidemia (MMA) is a common organic acidemia, mainly due to methylmalonyl-CoA mutase (MCM) or its coenzyme cobalamin (VitB12) metabolic disorders. Cobalamin C (CblC) type is the most frequent inborn error of cobalamin metabolism; it can develop symptoms in childhood and often combine multisystem damage, which leads to methylmalonic acid, propionic acid, methyl citrate, and other metabolites abnormal accumulation, causing nerve, liver, kidney, bone marrow, and other organ damage.

Patient concerns: A 4-year-old girl presented with paleness, fatigue, severe normochromic anemia, and acute kidney injury.

Diagnosis: Based on severe normochromic anemia and acute kidney injury, renal biopsy showed membranous proliferative glomerular lesions and thrombotic microvascular disease, supporting the diagnosis of aHUS. Although the serum vitamin B12 was normal, further investigation found the concentration of urinary methylmalonic acid and serum homocysteine increased obviously, genetic analysis revealed a heterozygous MMACHC mutation (exonl: c. 80A >G, c. 609G >A). The final diagnosis was aHUS induced by inherited methylmalonic acidemia (MMACHC heterozygous mutation exonl: c. 80A >G, c. 609G >A).

Interventions: The patient was treated with a 1mg vitamin B12 intramuscular injection daily for 4 days after which the dose was then adjusted to a 1mg intramuscular injection twice a week. At the same time, the girl was given levocarnitine, betaine, folic acid, along with supportive treatment.

Outcomes: After treated by vitamin B12 for 10 days, the patient condition significantly improved, Follow-up results showed complete recovery of hemoglobin and renal function.

Lessons: Although the majority of MMA onset from neurological damage, our case illustrates that partial CblC-type MMA can onset with severe metabolic aHUS. On the basis of chronic thrombotic microangiopathy (TMA)-induced renal damage, it can be complicated by acute hemolytic lesions. MMA should be considered in those patients with unclear microangiopathic hemolytic anemia accompany significant megaloblastic degeneration in bone marrow. We should pay attention to the causes and adopt a reasonable treatment strategy.

Figure 1

LM: (A) renal pathology suggests that there is severe extensive glomerulosclerosis, showing glomerular segmental basement membrane thickening, capillary endothelial cell swelling, and mild proliferation of segmental mesangial cells. Mesangial cells showed segmental insert phenomenon. Red blood cell debris was visible in part of the capillary blood vessels and polymorphonuclear leukocyte infiltration exists in part of the glomerulus. There is also an expansion in the glomerular Bowman's capsule cyst and a capillary loop ischemic shrinkage. There are moderate tubulointerstitial lesions, multifocal interstitial infiltration of renal interstitial cells with edema and fibrosis, multifocal lamellar tubular atrophy, part of the renal tubular epithelial cells swelling, vacuolar degeneration, and partial tubular expansion. Part of the tubule has tubular protein present and there is focal hyalinosis in the endomembrane of renal arterioles. (B) Light microscopy shows glomerular segmental basement membrane thickening and “double-track sign” formation.

Figure 2

EM: the glomerular mesangial matrix is grossly increased and there is a thickening and shrinkage of the GBM. There is a segmental inner tectorium widening, extensive foot process fusion and the capillary is obstructed. There are no electron dense deposits.

Figure 3

The MMACHC gene c. 80A >G and the MMACHC gene c. 609G >A. Heterozygous mutations were present in both, the patient (A) and her younger sister (D). The c. 80A site was not abnormal, but the c. 609G >A of MMACHC gene presented a heterozygous mutation in her mother (B). The MMACHC gene c. 609G site was normal, but c. 80A >G presented a heterozygous mutation in her father (C).

Figure 4

Follow-up of blood routine test.

Figure 5

Follow-up of serum creatinin.