This case highlights the importance of further studies of the correlation of genotype and phenotype.
During the presentation of the case in the Journal of Medicine and Public Health, study co-author Dr. Jose Pascual. Photo: Video Capture.
As study co-author Dr. Jose Pascual explained, these are six new cases that were referred to a genetics clinic for a variety of reasons, including hypotonia, speech and developmental delays, behavioral and sensory problems.
The specialist indicated that the patients ranged in age from 2 months to 3 years, “and initial assessment included metabolic profiles, including VMP, CBC, organic acids in blood and urine, and carnitine profiles.”
He stressed that once the study was done, it was determined that the patients had multiple mutations in the ACADS, SLC22A5 and HADHB genes.
“These tests showed that the patients had fatty acid metabolism deficits, therefore, the patients were sent to a genetic panel and the results showed that all patients had mutations in genes associated with fatty acid metabolism deficiency, in addition to their mutations. were in the ACADS, SLC22A5 and HADB genes”, he explained.
“Considering the consequences of failures in these genes, patients were diagnosed with short-chain dehydrogenase deficiency. The disease is characterized by an inability to metabolize fatty acids that are composed of 6 carbons or less. “, explained Dr. Pascual.
Because of this inefficiency, some metabolites accumulate, “which in our patients (…) would be organic acids, which are characteristic of the disease, in addition, elevated plasma lactate can also be observed,” he added. .
They reported that the intervention was a medical and nutritional management regimen that implemented carnitine, vitamin C and complex B, as well as a nutritional regimen in which calories were divided by macronutrients between carbohydrates, proteins and fats into estimated calories 20, 25 it was done. 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, as can be seen in our patients, because there are mutations that are 625A, 511T”, he explained. . ,
He noted 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, along with the case authors, considers it important to study the pathophysiological mechanisms of metabolites. “Our patients show elevations in organic acids with low carnitine.”
They stressed that the outcome 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. Additionally, there may also be an epigenetic factor in Puerto Ricans.”
The authors of the study are: Dr. Jose Pascual, Dr. Orlando Quiscoses, Dr. Crystal Hernandez, Dr. Simon Carlow You geneticistDr Alberto Santiago Cornier.
View the presentation of the case:
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 caused by mutations in the ACADS gene (12q24.31) encoding the short-chain acyl-CoA dehydrogenase C2 to C3, as well as additional as yet unknown triggering factors.
SCAD deficiency is defined as the presence of increased concentrations of butyrylcarnitine (C4) in plasma, increased concentrations of ethylmalonic acid (EMA) in the urine, or both, in non-stress conditions (at least two occasions ) and under homozygous mutations in the ACADS gene or in susceptibility-associated variants: C. 511C>T&C.625G>A.
Differential diagnosis includes multiple acyl-CoA dehydrogenase (MADD) deficiency, ethylmalonic encephalopathy, and acute ackee fruit poisoning.