ABSTRACT
Objective@#To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ.@*Methods@#GCDH gene variants was detected by Sanger sequencing among the three children and their family members.@*Results@#Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c. 532G>A (p.Gly178Arg) and c. 655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c. 532G>A(p.Gly178Arg) and c. 655G>A (p.Ala219Thr) variants. Patient 2 carried c. 532G>A (p.Gly178Arg) and a novel c. 1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c. 532G>A (p.Gly178Arg) and c. 1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c. 532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers.@*Conclusion@#The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.
ABSTRACT
La aciduria glutárica tipo I se produce por deficiencia de la enzima glutaril-CoA deshidrogenasa involucrada en el catabolismo de la L-lisina, L-hidroxilisina y L-triptófano lo que ocasiona acumulación de los ácidos glutárico y 3 hidroxiglutárico responsables del compromiso neurológico severo característico de esta enfermedad. La sospecha y diagnóstico de las enfermedades metabólicas constituyen un reto para el personal de salud dada su baja incidencia. En el caso de la aciduria glutárica tipo I se trata de una enfermedad para la cual se poseen los recursos técnicos para el diagnóstico y tratamiento nutricional, su instauración previa a la aparición de encefalopatía aguda, que ocasionan daños irreversibles en el sistema nervioso central, mejora el pronóstico y disminuye el grado de discapacidad. En esta publicación se reportan 5 casos con diagnóstico clínico y bioquímico de aciduria glutárica tipo I que ilustran el espectro clínico y el proceso diagnóstico y de tratamiento en el medio colombiano. Los pacientes se encuentran en seguimiento por los servicios de Neuropediatría.
Glutaric aciduria type i is a disorder resulting trom the deficiency ot the glutaryl-CoA dehydrogenase, enzyme involved in the catabolism ot L-lysine, L-hydroxy-lysine y L-tryptophan causing the accumulation ot its derivatives glutaric acid and 3-hydroxy-glutaric acid which are responsible tor the severe neurological involvement observed in this disease. The diagnosis ot metabolic disorders represents a challenge tor health-care services given its low incidence. Glutaric aciduria type I is a disease tor which there are available technical resources tor diagnosis as well as the nutritional therapy that when set prior to acute encephalopathy, who results in irreversible damage ot central nervous system, can improve the prognosis and decrease the disability ot patients. This publication report 5 cases with clinical and biochemical diagnosis ot glutaric aciduria type i that show the clinical spectrum the diagnostic and treatment approach ot this pathology in Colombia. All the patients are being followed by neuropediatrics services.
ABSTRACT
Glutaric aciduria type I (GA I) is an autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase. Although over 400 patients confirmed as GA I have been reported, reports from the Asian population had contributed to the minor proportion. We recently diagnosed two cases of GA I confirmed with mutational analysis. Here, we present their rather atypical clinical presentations with genetic characteristics for the first time in Korea. Profound developmental delay from birth, association of hearing loss, and neurological improvement after surgical intervention, were considered to be different clinical features from most reported cases. One patient was a compound heterozygote for p.Ser139Leu and p.Asp220Tyr, and the other for p.Ser139Leu and Glu160X. The mutations of the two alleles (p.Asp220Tyr and p.Glu160X) were novel and reports of p.Ser139Leu were rare both in Western and other Asian populations. These might suggest different genetic spectrum of Korean GA I patients.
ABSTRACT
Glutaric aciduria type 1(GA1) is an autosomal recessive disorder of the lysine, hydroxylysine and tryptophan metabolism caused by the deficiency of mitochondrial glutaryl-CoA dehydrogenase. This disease is characterized by macrocephaly at birth or shortly after birth and various neurologic symptoms. Between the first weeks and the 4-5th year of life, intercurrent illness such as viral infections, gastroenteritis, or even routine immunizations can trigger acute encephalopathy, causing injury to caudate nucleus and putamen. But intellectual functions are well preserved until late in the disease course. We report a one-month-old male infant with macrocephaly and hypotonia. In brain MRI, there was frontotemporal atrophy(widening of sylvian cistern). In metabolic investigation, there were high glutarylcarnitine level in tandem mass spectrometry and high glutarate in urine organic acid analysis, GA1 was confirmed by absent glutaryl-CoA dehydrogenase activity in fibroblast culture. He was managed with lysine free milk and carnitine and riboflavin. He developed well without a metabolic crisis. If there is macrocephaly in an infant with neuroradiologic sign of frontotemporal atrophy, GA1 should have a high priority in the differential diagnosis. Because current therapy can prevent brain degeneration in more than 90% of affected infants who are treated prospectively, recognition of this disorder before the brain has been injured is essential for treatment.