Very-long chain acyl-coA dehydrogenase deficiency: report of a Chinese pedigree and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).@*METHODS@#A Chinese pedigree affected with VLCADD admitted at the First People's Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed.@*RESULTS@#The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14:1, C16:1, C16:2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c.664G>A (p.G222R) and c.1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14:1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c.1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120).@*CONCLUSION@#The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c.1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.

Clinical manifestation and gene analysis of a family with pseudoachondroplasia / 中华实用儿科临床杂志

Clinical manifestations and genes of a case from a family with pseudoachondroplasia caused by COMP gene mutation treated in the Department of Pediatrics of the First People′s Hospital of Yunnan Province were retrospectively analyzed.The male patient aged 3 years and 3 months old had a history of slow growth for 1 year.Physical examinations showed that the patient′s height: 87.5 cm (less than -3 SD), 55.0 cm on top, 32.5 cm on bottom, mild O-leg, Nervous system physical examination suggested normal muscle strength of lower limbs and low muscle tone.Genetic examination revealed that the heterozygous gene variation of exon 11 of the COMP gene was chr19: 18897437 A >g [hg19], nm_000095.2, c.1159T >c, p.CY3 387 Arg, namely the transformation of cysteine to arginine at position 1159 of the translation product protein.Genetic testing is an important basis for the diagnosis of pseudoachondroplasia.It can avoid mistreatment, so as not to affect the predicted adult height of children.