This case highlights the importance of further studying the correlation of genotype and phenotype.
Dr. José Pascual, co-author of the study during his presentation of the case to the Journal of Medicine and Public Health. Photo: Video capture.
As revealed by Dr. José Pascual, co-author of the study, these are six new cases that were referred to the genetics clinic for various reasons, including hypotonia, speech and developmental delay, behavioral and sensory problems.
The specialist indicated that the age of the patients ranged from 2 months to 3 years, “and the initial evaluation consisted of metabolic profiles, including VMP, CBC, organic acids in blood and urine and carnitine profile. ”.
He stressed that once the studies were carried out, it was determined that the patients had several mutations in the ACADS, SLC22A5 and HADHB genes.
“These tests showed that the patients had a deficiency of fatty acid metabolism, therefore, a genetic panel was sent to the patients and the results reflected that all the patients had mutations in genes associated with a deficiency of fatty acid metabolism, additionally they had mutations in the ACADS, SLC22A5 and HADB genes”, he explained.
“Taking into consideration the results of the failures in these genes, the patients were diagnosed with short-chain dehydrogenase deficiency. This disease is characterized by an inability to metabolize carbon fatty acids that are made up of 6 carbons or less”, explained Dr. Pascual.
He added that due to this inability, certain metabolites accumulate, “which would be organic acids in our patients (…), which are characteristic of the disease, in addition, elevated plasma lactate might also be seen,” he said.
He reported that the intervention was a medical and nutritional management in which carnitine, vitamin C and complex B were implemented, as well as a nutritional regimen in which calories were divided by macronutrients between carbohydrates, proteins and fats to approximate calories between 20 , 25, 55 percent. “All patients are clinically stable.”
“We believe that the relevance of this study lies in the need to further study the correlation of genotype and phenotype in this disease, because as can be seen, in our patients, because there are mutations that are 625A, 511T”, he explained. .
He added that these mutations are often classified as benign mutations, that is, they will not cause a phenotype, “but in a certain part of the literature it has been possible to see patients with these mutations with a phenotype and these six patients are part of this literature,” he said.
He emphasized that he, together with the authors of the case, consider it important to study the pathophysiological mechanism of the metabolites. “Our patients reflect an elevation of organic acids with low carnitine.”
He stressed that the result of this metabolic profile is contributing to the phenotype of these patients. “We believe that cell models can be developed to study the contribution of these genetic variants further. Additionally, there might also be an epigenetic factor in Puerto Ricans.”
The authors of the study are: Dr. Jose Pascual, Dr. Orlando Quiscoses, Dr. Cristal Hernandez, Dr. Simon Carlo y the geneticistDr. Alberto Santiago Cornier.
See the case presentation:
Short-chain acyl-CoA dehydrogenase deficiency (SCADD)
The literature indicates that short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a very rare congenital disorder of fatty acid oxidation in mitochondria. It is inherited in an autosomal recessive manner.
SCADD is due to mutations in the ACADS gene (12q24.31) encoding short-chain acyl-CoA dehydrogenase C2 to C3, as well as additional yet unknown triggers.
SCAD deficiency has been defined as the presence of an increased concentration of butyrylcarnitine (C4) in plasma, an increased concentration of ethylmalonic acid (EMA) in urine, or both, under non-stress conditions (in al least two occasions) and homozygous mutations in the ACADS gene or variants associated with susceptibility: c. 511C>T and c.625G>A.
The differential diagnosis includes multiple acyl-CoA dehydrogenase (MADD) deficiency, ethylmalonic encephalopathy, and acute ackee fruit poisoning.