Concurrent combined methylmalonic acidemia and homocystinuria with down syndrome in a Chinese preschool Child: An in-depth case report and literature review
Rui Dong,
Chen Liu,
Yulin Liu,
Haiyan Zhang,
Guohua Liu,
Yi Liu,
Zhongtao Gai
Affiliations
Rui Dong
Pediatric Research Institute, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China; Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China
Chen Liu
Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China; Neonatology department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China
Yulin Liu
Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China; Department of neuroelectrophysiology, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China
Haiyan Zhang
Pediatric Research Institute, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China; Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China
Guohua Liu
Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China; Department of Pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital, Jinan), Jinan, China; Corresponding author. Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China.
Yi Liu
Pediatric Research Institute, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China; Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China; Corresponding author. Pediatric Research Institute, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
Zhongtao Gai
Pediatric Research Institute, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China; Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China
Background: Dual occurrence of distinct genetic diseases is exceptionally rare, complicating both diagnosis and management when the conditions share overlapping symptoms. Case presentation: We describe a preschooler girl diagnosed with Down syndrome at 27 months who developed unexplained motor regression with age. Extensive investigations were carried out to elucidate the etiology, encompassing comprehensive neuromuscular and skeletal assessments, radiographic evaluations of the joints, electrophysiological studies, cerebral-spinal magnetic resonance imaging (MRI), hematological biochemical assays, plasma ammonia and lactate levels, full blood count analyses, echocardiography, and chromatography-mass spectrometry-based testing of amino acids, fatty acids, and organic acid metabolites in both blood and urine. Notably, significantly elevated levels of homocysteine and propionylcarnitine were detected in her blood, while urinary methylmalonic acid was also found to be abnormally high. Trio-whole exome sequencing confirmed the diagnosis as Combined methylmalonic acidemia and homocystinuria (Combined MMA and HCU), specifically due to a cblC defect, resulting from two compound heterozygous pathogenic mutations (c.217C > T and c.482G > A) in the MMACHC gene. Upon a two-month course of treatment with hydroxocobalamin and l-carnitine, the patient demonstrated moderate improvement in her motor abilities. Conclusion: Our study highlights the special and intriguing aspects of managing Combined MMA and HCU, emphasizing the value of a comprehensive diagnostic approach that integrates clinical acumen, metabolic screening, and sophisticated molecular analyses for achieving precise diagnoses in such intricate cases.
