ABSTRACT
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive hereditary metabolic disorder of mitochondrial fatty acid beta-oxidation. It is characterized by hypoketotic hypoglycemia, hyperammonemia, seizure, coma, and sudden infant death syndrome-like illness. The most frequently isolated mutation in the acyl-CoA dehydrogenase, medium-chain (ACADM) gene of Caucasian patients with MCADD is c.985A>G, but ethnic variations exist in the frequency of this mutation. Here, we describe 2 Korean pediatric cases of MCADD, which was detected during newborn screening by tandem mass spectrometry and confirmed by molecular analysis. The levels of medium-chain acylcarnitines, including octanoylcarnitine (C8), hexanoylcarnitine (C6), and decanoylcarnitine (C10), were typically elevated. Molecular studies revealed that Patient 1 was a compound heterozygote for c.449_452delCTGA (p.Thr150ArgfsX4) and c.461T>G (p.L154W) mutations, and Patient 2 was a compound heterozygote for c.449_452delCTGA (p.Thr150ArgfsX4) and c.1189T>A (p.Y397N) mutations. We detected asymptomatic patients with MCADD by using a newborn screening test and confirmed it by ACADM mutation analysis. This report presents evidence of the biochemical and molecular features of MCADD in Korean patients and, to the best of our knowledge, this is the first report of the c.461T>G mutation in the ACADM gene.
Subject(s)
Female , Humans , Infant, Newborn , Male , Acyl-CoA Dehydrogenase/chemistry , Asian People/genetics , Base Sequence , Biomarkers/blood , Carnitine/analogs & derivatives , DNA Mutational Analysis , Exons , Gene Deletion , Heterozygote , Lipid Metabolism, Inborn Errors/diagnosis , Mutation , Neonatal Screening , Republic of Korea , Tandem Mass SpectrometryABSTRACT
Sandhoff disease is a rare autosomal recessive metabolic disease presenting bilateral optic atrophy and a cherry red spot in the macula. This case report presents the characteristics of a patient with Sandhoff disease as assessed by ophthalmic, neuroimaging, and laboratory procedures. Ophthalmologic examination revealed that the patient could not fixate her eyes on objects nor follow moving targets. A pale optic disc and a cherry red spot in the macula were seen in both eyes. Low signal intensity at the thalamus and high signal intensity at the cerebral white matter were noted in a T2-weighted brain MR image. A lysosomal enzyme assay using fibroblasts showed the marked reduction of both total beta-hexosaminidases, A and B. Based on the above clinical manifestations and laboratory findings, we diagnosed the patient as having Sandhoff disease.
Subject(s)
Child, Preschool , Female , Humans , Atrophy , Cerebral Cortex/pathology , Isoenzymes/deficiency , Lipid Metabolism, Inborn Errors/diagnosis , Magnetic Resonance Imaging , Ocular Motility Disorders/diagnosis , Optic Disk/pathology , Retinal Diseases/diagnosis , Sandhoff Disease/diagnosis , Thalamus/pathology , beta-N-Acetylhexosaminidases/deficiencyABSTRACT
Las miopatías por depósito de lípidos son la expresión fundamental de los trastornos del metabolismo lipídico muscular. En el presente estudio exponemos cuatro casos de la entidad y señalamos las características clínicas, histopatológicas y bioquímicas que están presentes en los defectos genéticos del metabolismo de los ácidos grasos del músculo esquelético. En tres casos los hallazgos fueron compatibles con el diagnóstico de la entidad por déficit de carnitina y en uno por déficit de flavoproteínas. Tres correspondieron a pacientes del sexo femenino. Concluimos que con una correlación sistemática de los datos clínicos y paraclínicos, así como también del estudio morfológico, se puede inferir la posible etiología de estas miopatías, cuyo diagnóstico definitivo es por medio del análisis bioquímico
Subject(s)
Humans , Male , Adolescent , Adult , Female , Infant , Metabolic Diseases/diagnosis , Metabolic Diseases/etiology , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/metabolism , Lipid Metabolism, Inborn Errors/pathology , Muscular Diseases , Muscle, Skeletal/abnormalities , Medicine , VenezuelaABSTRACT
Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the commonest inherited disorder of fatty acid oxidation. Most clinically ascertained cases are caused by thc point mutation K329E in MCAD gene. The frequency of this mutation as determined by usc of dried blood spots on Guthrie cards and the PCR NeoI digestion method. Using molecular ncwborn screening we found no K329E homozygote and 14 K329E heterozygotes in 2,826 newborns from Moravian area of the Czech Republic. Lower frequency of K329E carriers (1/202)) suggests that the incidence of MCAD deficiency will be probably lower in our population than we expected.