Diagnosis of cobalamin C deficiency with renal abnormality from onset in a Chinese child by next generation sequencing: A case report

Abstract

The aim of the present study was to present the diagnosis and treatment course of a patient with cobalamin C deficiency (cblC) hospitalized with renal function abnormality from the onset. A female, 7-year-old patient who presented with a cough and progressive dyspnea for 1 day was admitted to the Children's Hospital of Nanjing Medical University (Nanjing, China). A routine clinical examination was performed, including physical examination, routine blood and urine tests, blood gas analysis, computed tomography scans of the head, chest and abdomen, electrocardiogram, echocardiography and abdominal ultrasonography. In addition, laboratory tests were performed, including tests for viral infection and markers of autoimmunity, humoral immunity, myocardial enzymes and tumors. Tandem mass analysis and renal biopsy were conducted. Next generation sequencing (NGS) was performed to identify mutated genes, and structural investigation was conducted to identify the key residue mutations in the patient. Routine clinical examination revealed that the patient had multiple organ failure, indicating the presence of metabolic disease. Tandem mass analysis and renal biopsy also indicated that the patient had methylmalonic acidemia (MMA) and thrombotic microangiopathy combined with focal renal cortical necrosis. Furthermore, next-generation sequencing identified the presence of two heterozygous mutations in the MMA cblC type with homocystinuria (MMACHC) gene. Structural analysis demonstrated that the two mutations were in key components of the MMACHC protein. The patient was finally diagnosed with cblC according to the results obtained. In conclusion, NGS may aid in the diagnosis and therapeutic management of cblC with renal abnormality from the onset in children.

Case Report: Membranous Nephropathy Secondary to Cobalamin C Disease

“…In the present case, the diagnosis took 9 months after initiation of the renal injury. Some patients are not diagnosed until their condition has progressed to irreversible kidney injury (11). We previously described another 20-year-old female patient with IgA nephropathy associated with cblC who presented with neurological symptoms.…”

A 7-Year Report of Spectrum of Inborn Errors of Metabolism on Full-Term and Premature Infants in a Chinese Neonatal Intensive Care Unit

“…Genomic DNA was extracted from peripheral blood leukocytes obtained from the patients using a QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany). The lists of known inheritable genetic disease-related genes in the panels for captured and targeted next-generation sequencing were described previously (Yang et al, 2013;Chen et al, 2017). The amplified DNA was specifically enriched using a biotinylated capture probe (MyGenostics, MD, USA).…”

Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report

“…Collectively, hereditary metabolic diseases in the neonatal period often lead patients to deteriorate rapidly. Therefore, early recognition of the disease by clinicians is of great importance (13). The findings of the present study suggest that blood ammonia monitoring should be carried out in cases where seemingly healthy newborns display uncommon symptoms several days after milk intake, in order to exclude UCD.…”

“…Upon admission, routine examinations, including physical examination, urinalysis, blood gas analysis, and blood examination, were performed as described previously (11,12). In addition, laboratory tests for C-reactive protein, pro-calcitonin, toxoplasma, rubella, cytomegalovirus and herpes simplex viruses, respiratory viruses (influenza virus, respiratory syncytial virus and adenovirus), biochemistry, routine cerebrospinal fluid analysis, blood ammonia, blood glucose, lactic acid, liver function and renal function were performed (12,13). Bacterial cultures of blood, urine, and cerebrospinal fluid samples were conducted.…”