Search results for "Inborn"
showing 10 items of 62 documents
Molybdenum Trioxide Nanoparticles with Intrinsic Sulfite Oxidase Activity
2014
Sulfite oxidase is a mitochondria-located molybdenum-containing enzyme catalyzing the oxidation of sulfite to sulfate in the amino acid and lipid metabolism. Therefore, it plays a major role in detoxification processes, where defects in the enzyme cause a severe infant disease leading to early death with no efficient or cost-effective therapy in sight. Here we report that molybdenum trioxide (MoO3) nanoparticles display an intrinsic biomimetic sulfite oxidase activity under physiological conditions, and, functionalized with a customized bifunctional ligand containing dopamine as anchor group and triphenylphosphonium ion as targeting agent, they selectively target the mitochondria while bein…
Congenital Cystic Lesions of the Bile Ducts: Imaging-Based Diagnosis
2020
Congenital cystic lesions of the bile ducts represent a spectrum of liver and biliary system lesions, resulting from abnormal embryologic development of the ductal plate. These disorders include Caroli disease, choledochal cysts, autosomal dominant polycystic liver disease, congenital hepatic fibrosis, and biliary hamartomas. Each disorder carries a peculiar clinical presentation, prognosis, and risk of complications. Knowledge of radiological findings of fibropolycystic liver diseases is crucial for their appropriate detection and for differential diagnosis with other similar hepatic cystic lesions, in order to avoid relevant misdiagnosis. The aim of this review is to provide an illustrati…
Abnormal Hypermethylation at Imprinting Control Regions in Patients with S-Adenosylhomocysteine Hydrolase (AHCY) Deficiency
2016
S-adenosylhomocysteine hydrolase (AHCY) deficiency is a rare autosomal recessive disorder in methionine metabolism caused by mutations in the AHCY gene. Main characteristics are psychomotor delay including delayed myelination and myopathy (hypotonia, absent tendon reflexes etc.) from birth, mostly associated with hypermethioninaemia, elevated serum creatine kinase levels and increased genome wide DNA methylation. The prime function of AHCY is to hydrolyse and efficiently remove S-adenosylhomocysteine, the by-product of transmethylation reactions and one of the most potent methyltransferase inhibitors. In this study, we set out to more specifically characterize DNA methylation changes in blo…
Quantitative Acylcarnitine Profiling in Peripheral Blood Mononuclear Cells Using In Vitro Loading With Palmitic and 2-Oxoadipic Acids: Biochemical Co…
2005
Organic acid (OAD) and fatty acid oxidation disorders (FAOD) are inborn errors of metabolism often presenting with life-threatening metabolic decompensation followed by (irreversible) organ failure, and even death during catabolic state. Most of these diseases are considered as treatable, and metabolic decompensations can be avoided by early diagnosis and start of therapy. Confirmation of suspected diagnosis currently relies on enzymatic and mutation analyses and in vitro loading of palmitic acid in human skin fibroblast cultures. Furthermore, in some cases potentially life-threatening in vivo loading or fasting tests are still performed. In this study, we established a standardized in vitr…
Laboratory investigations in genetic syndromes: examples of clinical approach in the neonatal unit.
2010
Contiguous gene deletion syndromes: the importance of an accurate genetic definition for a careful clinical monitoring. Contiguous gene deletion syndromes are so named because the deletion manifests as a distinctive cluster of otherwise unrelated single-gene disorders in the same subject. An accurate genetic definition of the deleted region is extremely important for the appropriate management of these patients and for unravelling the function of the involved genes. The microarray-based comparative genomic hybridization (CGH arrays) analysis is the actual molecular method able to accurately define the bounds of a deleted region, since it allows an evaluation of DNA copy number alterations a…
Liver pathology in transient neonatal hyperammonemia.
1983
Ultrastructural investigations have been performed on two cases of transient neonatal hyperammonaemia (TNH). This newly recognized metabolic disorder is chiefly characterized by severe hyperammonaemia in the postnatal period, a comatous state, absence of abnormal organic aciduria, normal activity of urea cycle enzymes and, usually, complete recovery. The aetiology is presently unknown. Electron microscopy uncovered rather congruent alterations of hepatocyte structure, with a wide spectrum of mitochondrial lesions, an increase of autophagous bodies with organelle remnants, and changes in the excretory apparatus. Thus, in contrast to some of the hereditary disorders of the urea cycle, no spec…
Newborn screening and disease variants predict neurological outcome in isovaleric aciduria.
2021
Isovaleric aciduria (IVA), a metabolic disease with severe (classic IVA) or attenuated phenotype (mild IVA), is included in newborn screening (NBS) programs worldwide. The long-term clinical benefit of screened individuals, however, is still rarely investigated. A national, prospective, observational, multi-center study of individuals with confirmed IVA identified by NBS between 1998 and 2018 was conducted. Long-term clinical outcomes of 94 individuals with IVA were evaluated, representing 73.4% (for classic IVA: 92.3%) of the German NBS cohort. In classic IVA (N = 24), NBS prevented untimely death except in one individual with lethal neonatal sepsis (3.8%) but did not completely prevent si…
Clinical manifestations and management of four children with Pearson syndrome.
2011
Pearson marrow-pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non-hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease.
Exome sequencing in suspected monogenic dyslipidemias.
2015
Background— Exome sequencing is a promising tool for gene mapping in Mendelian disorders. We used this technique in an attempt to identify novel genes underlying monogenic dyslipidemias. Methods and Results— We performed exome sequencing on 213 selected family members from 41 kindreds with suspected Mendelian inheritance of extreme levels of low-density lipoprotein cholesterol (after candidate gene sequencing excluded known genetic causes for high low-density lipoprotein cholesterol families) or high-density lipoprotein cholesterol. We used standard analytic approaches to identify candidate variants and also assigned a polygenic score to each individual to account for their burden of commo…
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a severe fatty acid oxidation disorder
1994
3-Hydroxyacyl-CoA dehydrogenase deficiency is a newly recognised fatty acid oxidation disorder with a usually fatal outcome. We present a further patient who presented with hypoketotic hypoglycaemia, hepatopathy, secondary carnitine deficiency and increased plasma long-chain acylcarnitines. 3-Hydroxydicarboxylic aciduria was present and the diagnosis confirmed in cultured skin fibroblasts. Our patient is compared with those reported in the literature with respect to clinical symptoms, differential diagnosis and possible therapeutic regimens.