Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations
The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic acidemia and homocystinuria in plasma, is an inborn error of cobalamin metabolism. The late-onset cblC siblings patients were rarely reported. In this study, we analyzed the clinical presentations and treatment outcomes of late-onset cblC in Chinese sibling patients with neuropsychiatric presentations. The clinical data of four pairs of Chinese patients were retrospectively analyzed. Serum homocysteine, urine organic acids measurements, neuroimaging exams and gene analysis were carried out in all patents. Patients were reevaluated after treatments with cobalamin, folate, betaine, L-carnitine and compound vitamin B. The mean age at disease onset was 13.7 (range 2–19) years. The neuropsychiatric disturbances including cognitive decline (3/8), psychiatric disturbances (4/8), gait instability (2/8), lower extremity weakness and numbness (3/8) and thromboembolic events (1/8). Two patients suffered nephropathy. The mean serum homocysteine when patients were diagnosed was 109.4 (range 69.5–138) μM/L. The abnormal radioimaging included scoliosis by X-ray (5/6), cerebral atrophy (4/6) and spinal cord atrophy (3/6) by MRI scan. Three pairs of siblings showed heterozygous mutations of MMACHC gene including c.482G > A (4/6), c.354G > C (2/6), c.570insT (2/6), c.445_446del (2/6) and c.656_4658del (2/6). The other two siblings showed homozygous mutation with c.452A > G in MMACHC gene. After treatments, the psychiatric symptoms were obviously relieved in all the patients. In Chinese siblings with late-onset cblC, the main clinic manifestation and abnormal radioimaging were cognitive decline and cerebral atrophy respectively. The most common gene mutation was c.482G > A of MMACHC gene. The patients responded well to the treatments.
KeywordsCobalamin Methylmalonic acidemia Homocystinuria Late onset Sibling
This work is supported by grants from Natural Science Foundation of Shandong Province, China (No.ZR2017MH082) and Innovative Research Project of Resident Standardization Training of Qilu Hospital, Shandong University (No.ZPZX2017B10).
Dr. Sheng-jun Wang was responsible for the analysis of data and drafting of the manuscript.
Chuan-zhu Yan was responsible for the interpretation of data and revision of the manuscript.
Yi-ming Liu was responsible for interpretation of clinical data and revision of manuscript.
Dr. Yu-ying Zhao was responsible for critical revision and final approval of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors report no disclosures relevant to the manuscript. There are no conflicts of interest in this manuscript.
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