ABSTRACT
El síndrome de Sjogren-Larsson se caracteriza por retardo mental, ictiosis congènita y diplejía o cuadriplejía espástica. El defecto primario en este síndrome es la mutación del gen ALDH3A2, que codifica la enzima aldehído deshidrogenasa grasa y causa una deficiencia enzimática que produce una acumulación de alcoholes y aldehídos grasos en los tejidos que comprometen la integridad de la membrana celular, cuyos efectos pueden observarse en la piel, los ojos y el sistema nervioso central. El diagnóstico se realiza por medio de la cuantificación de la actividad de la enzima. Se describe el caso de una paciente con signos clínicos patognomónicos del síndrome de Sjogren-Larsson, cuyo diagnóstico se realizó por medio de la cuantificación de la actividad enzimática en un cultivo de fibroblastos. Además, tomando en cuenta el árbol genealógico de la paciente, se realizó el estudio en los padres y un hermano con signos sugestivos del síndrome de Sjogren-Larsson.
Sjogren-Larsson syndrome is characterized by congenital ichthyosis, mental retardation and spastic diplegia or quadriplegia. The primary defect in this syndrome is mutation of ALDH3A2 gen that codes for the fatty aldehyde dehydrogenase. Deficiency of this enzyme causes an accumulation of fatty alcohols and fatty aldehydes, leading to altered cell-membrane integrity. Skin, eyes, and the central nervous system are affected latter. The diagnosis is carried out through the cuantification of the enzyme activity.
Subject(s)
Humans , Female , Child , Sjogren-Larsson Syndrome/diagnosis , Aldehyde Oxidoreductases/genetics , Sjogren-Larsson Syndrome/genetics , Fibroblasts/enzymology , MutationABSTRACT
Objective: The polymorphic human liver enzyme alcohol dehydrogenase [ADH] is responsible for the oxidative metabolism of ethanol. An allele encoding active form of cytosolic enzyme is known to reduce the likelihood of alcoholism in Iraqi men. The polymorphisms of ADH modifies the predisposition to the development of alcoholism. Determination of genotypes ADH2 and ADH3 loci in alcoholic and nonalcoholic Iraqi men
Method: Using leukocyte DNA extraction and then amplifying by polymerase chain reaction [PCR] by using specified primers, then allele specific primer extension and PCR-restriction fragment length polymorphism [RFLP] methods with another set of primers is employed in order to determine the variants of ADH2 and ADH3, respectively
Results: The Iraqi alcoholics had significantly lower frequencies of ADH2*2 and ADH3*1 alleles than did the non-alcoholic as compared with the general population of East Asians but more than in Caucasians population, suggesting that genetic variation in ADH enzyme modulating the rate of metabolism of ethanol to acetaldehyde influences drinking and the risk of developing alcoholism. The simplest explanation of the significant lower frequency of ADH2*2 and ADH3*1 alleles among Iraqi alcoholic men is that each can produce higher transient level of acetaldehyde, which trigger aversive reactions; these alleles are less likely to become alcoholic
Conclusion: This study suggests that both ADH2 and ADH3 genotypes exert an influence on alcohol metabolic rate, alcohol-flush reaction and susceptibility to develop alcoholism. ADH2 and ADH3 genotypes may have a protective role in the risk for alcoholism in Iraqi alcoholic population