
The cblC deficiency is a common type of cobalamin metabolic disorder. The cblC deficiency is the most common type of MMA in China [4]. The cblC deficiency patients could present anorexia, progressive encephalopathy, renal dysfunction and hematologic abnormalities [3]. Early diagnosis is very important, which is underscored by gradual progression of the impaired system. The cblC deficiency is triggered by mutation in the MMACHC gene. More than 100 mutations in the MMACHC gene have been reported up to now [ G in Chinese children with cobalamin C deficiency. Front Pediatr. 2022;10:1057594.” href=”#ref-CR5″ id=”ref-link-section-d374650835e532″>5].In this patient, we found 2 heterozygous mutations: c.482G > A (p. R161Q) and c.658_660del (p. K220del). These 2 mutations have been reported in previous cases [6, 7]. The MMACHC gene mutation c.482G > A has been repeatedly reported with late-onset presentation [3]. Adult-onset cblC deficiency was found the first onset symptoms at the age after 18 years old. In adult-onset cblC deficiency patients, neurological symptoms, isolated psychiatric symptoms and renal involvement are main onset symptoms. With the progress of disease, the manifestations related to neuropathy and cognitive decline are common symptoms. Vascular disease (thromboembolic disease) and renal disease (proteinuria and renal failure) are also found in these patients [8]. The average level of serum homocysteine at diagnosis was 137.4 µmol/L (27.9–288 µmol/L) [8]. The level of serum homocysteine in this patient (481.7 µmol/L) was much higher than the average level. The treatment results in adult-onset patients are always with marked improvement. We need to raise awareness for this rare but treatable disease.
The cblC deficiency has been related to neurocognitive and vascular disorders. Thromboembolic complications including recurrent venous thrombosis, pulmonary thrombosis, cor pulmonale and cerebrovascular complications are important conditions in cblC deficiency patients [1]. Thrombotic microangiopathy and pulmonary arterial hypertension presented in cblC deficiency patients [9, 10]. Wide vascular lesions, such as arteriosclerosis, also presented in these patients [11]. Endothelial dysfunction has been regarded as an important pathogenesis of thrombotic microangiopathy, pulmonary arterial hypertension and arteriosclerosis. To the best of our knowledge, aortic dissection in cblC deficiency patients has not been reported. We may wonder what caused aortic dissection in a young man. The common risk factors of aortic dissection include hypertension, atherosclerosis, congenital diseases, trauma, inflammation, infection and others. The specific risk factors in this patient were male sex and stage 1 hypertension. He was healthy with no drugs previously. The targeted NGS panel indicated no suspicious heritable thoracic aortic diseases inducing aortic dissection. We suspected whether cblC deficiency caused aortic dissection. Hyperhomocysteinemia is a critical biomarker of the cblC deficiency. Epidemiological studies have suggested an association of hyperhomocysteinemia and aortic dissection, but discrepancies exist. It has been proven that hyperhomocysteinemia is a risk factor for arterial endothelial dysfunction [12]. 48% patients with abdominal aortic aneurysm were found hyperhomocysteinemia and the levels of plasma homocysteine were higher in patients than in control subjects [13]. In Marfan patients, severe cardiovascular manifestations and aortic dissection were found to be related with homocysteine plasma levels [14]. In addition, the levels of median plasma homocysteine were higher in patients with spontaneous cervical artery dissection than in control subjects [13]. Homocysteine plays a significant role in development of aortic dissection and homocysteinemia is a risk factor for aortic dissection. Impaired fibrillin deposition into extracellular matrix was found in aortic aneurysm and dissection. In the FBN1 (the gene for fibrillin-1) mutation patients, reduced fibrillin-1 deposition into pericellular matrix formed weakness of elastic tissue, which could cause aortic aneurysms or dissections. Fibrillin-1 regarded as the important component in extracelluar connective tissue was susceptible to homocysteine attack and irreversible homocysteinylation of long-lived proteins should cause cumulative damage and progressive clinical manifestations [13]. Moreover, homocysteine could cause premature breakdown in arterial elastic fibers by activating the elastolytic activities [13]. Thus, we hypothesized that elevated homocysteinemia in this patient was closely associated with aortic dissection.
Renal disease and chronic kidney disease are considerable manifestations of cblC deficiency. Renal complications induced by cblC disease include tubulointerstitial nephritis, thrombotic microangiopathy, hemolytic uremic syndrome and proximal renal tubular acidosis [15, 16]. A study reviewed the kidney involvement in adult-onset cblC deficiency patients [8]. Glomerular disease, renal failure and hemolytic uremic syndrome were commonly found. Kidney biopsies in adult-onset patients usually showed the typical lesions of thrombotic microangiopathy, which was similar with renal damage in infancies with cblC deficies. However, the kidney dysfunction in this case was a process of AKI, caused by aortic dissection. Through symptomatic treatment, his kidney function greatly improved.
In conclusion, we demonstrated a case of cblC deficiency with aortic dissection. This may contribute to the diagnosis of cblC deficiency. It is important to pay more attention to the early diagnosis and treatment of cblC deficiency.
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- Source: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-023-03414-9