![]() ![]() Diagnosis of fatty acid oxidation disorders and several organic acidurias in plasma specimens Evaluating treatment during follow-up of patients with fatty acid beta. Background Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. The topic of inborn errors of metabolism is challenging for most physicians. The number of known metabolic disorders is probably as large as the number of presenting. ![]() MRI of the Neonatal Brain. Metabolic disorders in theneonate. Zoltan Patay, Nicola J Robertson and I Jane Cox. Chapter Contents. Metabolic diseases are classically divided into two groups: inborn errors of metabolism and acquired metabolic disorders. Inborn errors of metabolism present with systemic metabolic abnormalities (acidosis, ketosis, ketoacidosis, etc.) and/or clinical signs and symptoms related to the involvement of one or more of the organ systems. These include the central and the peripheral nervous system (spinal cord, brain stem, cerebellum, basal ganglia, cerebral white and gray matter or peripheral nerve lesions), the musculoskeletal system (myopathy, dysostosis), some of the visceral organs (cardiomyopathy, hepatosplenomegaly) and even the skin (alopecia, dermatitis, petechiae). They include l- 2- hydroxyglutaric aciduria, glutaric aciduria type 1, 4- hydroxybutyric aciduria, alpha- ketoglutaric aciduria, mevalonic aciduria and N- acetylaspartic aciduria (Canavan’s disease), none of which is encountered in neonates. Some of the metabolic disorders have no neurological manifestations at all (e. They often present with disturbances of the central nervous system but there are few reports of associated brain imaging abnormalities. In acquired metabolic disorders, neurological complications may occur as a direct effect of the abnormality, from associated hypoxic– ischemic injury or may be secondary to the treatment. Benign forms of hyperbilirubinemia are often seen in neonates and typically resolve without sequelae; however, delayed or inappropriate treatment of more severe forms potentially leads to basal ganglia disease. Kernicterus is associated with abnormalities within the globus pallidum, subthalamic nuclei and hippocampus. Spectroscopy in this disorder may be unremarkable (Fig. Hypoglycemia is a relatively common cause for admission on to a neonatal unit and is occasionally associated with severe white matter injury (see Chapter 6). In the devastating metabolic diseases the underlying metabolic derangements result in global brain toxicity leading to diffuse brain edema and neurological manifestations that reflect the varying patterns and degrees of white or gray matter involvement. The clinical hallmarks of the condition are poor feeding, vomiting, seizures, stupor and lethargy rapidly leading to deep coma and subsequently to death or severe neurological impairment in the survivors. Some diseases are exclusive to the neonatal age group; the onset of the underlying metabolic derangement may, however, be either pre- or postnatal. 231680 - multiple acyl-coa dehydrogenase deficiency; madd - glutaric acidemia ii;; glutaric aciduria ii;; ga ii;; ethylmalonic-adipicaciduria; ema. UCSF Clinical Laboratory Testing Listing. An infant reference range has not been experimentally determined using our current PTT reagent. Neonatal or early infantile onset is usually related to a more profound metabolic derangement, whereas later onset often but not always reflects a less severe metabolic derangement with better prognosis. In others clinical signs and symptoms develop a few days later (isovaleric acidemia, methylmalonic acidemia, propionic acidemia, non- ketotic hyperglycinemia, citrullinemia, argininosuccinic aciduria). Maple syrup urine disease (MSUD) typically presents 6–7 days after birth. A significant proportion of metabolic diseases with clinical onset after the 4th week of life are considered to be early or late infantile, childhood and juvenile, and are not therefore discussed here. In some of the diseases imaging studies may reveal malformations of the brain, for example cortical dysplasia in Zellweger syndrome, callosal hypoplasia in non- ketotic hyperglycinemia. Malformations of the brain always suggest a profound metabolic derangement of prenatal onset. Abnormal odor of the skin, hair, earwax or urine is a frequent and often characteristic feature of metabolic diseases, for example . Ophthalmological abnormalities may provide useful additional clues to the diagnosis, for example cataract in rhizomelic chondrodystrophia punctata, retinal degeneration in Zellweger syndrome. Fatty acid oxidation disorders typically present with hepatosplenomegaly, myopathy and cardiomyopathy. On neurological examination, neonates with urea cycle defects, non- ketotic hyperglycinemia and peroxisomal disorders typically present with severe hypotonia. In a few other diseases, such as MSUD, episodes of hypertonia (opisthotonus) may alternate with hypotonia. In organic acidemias both hypotonia (e. ![]() Hypertonia (contractures) is characteristic in rhizomelic chondrodystrophia punctata. In fatty acid oxidation disorders epileptic seizures are related to hypoglycemia. This may result in confusing clinical presentations potentially leading to a delay in diagnosis and treatment. Routine biochemical findings are often non- specific but may be suggestive or characteristic of certain disease groups or even disease entities. Analysis of blood p. H, glucose, ammonia, lactic acid, urine ketone bodies and hepatic profile provides useful baseline information and guide any further diagnostic work- up. It is usually normal or borderline elevated in MSUD, and markedly elevated in both urea cycle defects and organic acidemias. If blood ammonia level is higher than 1. These two groups can be differentiated from each other by determining the blood p. H, which will reveal a respiratory alkalosis in the former and a metabolic acidosis in the latter. A blood sugar level assessment is also important. Maple syrup urine disease (MSUD), also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual. Features suggesting diagnosis other than SPG Motor Weakness > Spasticity Prominent upper limb spasticity Asymmetry Peripheral neuropathy. Find patient medical information for METHIONINE on WebMD including its uses, effectiveness, side effects and safety, interactions, user ratings and products that have it. Determination of the pyruvate–lactate ratio may be helpful in identifying the different forms, such as pyruvate dehydrogenase deficiency (pyruvate/lactate < 1/2. Adrenal insufficiency, sepsis, and dehydration may, however, also present with similar laboratory findings. Clinical and laboratory evidence of liver disease are typically present in fatty acid oxidation and oxidative phosphorylation disorders. High plasma levels of phytanic, pipecolic and very long chain fatty acids (VLCFA), as well as bile acid intermediates are typical findings in peroxisomal diseases. ![]() In addition there are specific enzyme studies, for example glutathione reductase assay of red blood cells in 5- oxoprolinuria, propionyl- Co. A carboxylase or HMG- Co. A lyase assay in white blood cells in propionic acidemia and HMG- Co. A lyase deficiency and pyruvate carboxylase or cytochrome c oxidase assay in liver or muscle biopsy specimen in oxidative phosphorylation disorders. To compensate for the longer T2 relaxation time (due to the high water and lower myelin/lipid content) of the brain parenchyma in the newborn and infant, longer repetition (TR) and echo (TE) times are used in T2 weighted imaging. Mid- line structures such as the corpus callosum and the cerebellar vermis are best assessed on sagittal images (Fig. The cerebellar white matter, the dentate (Fig. Fig. 1. 7. 3) and the tails of the caudate nuclei are best imaged in the coronal plane. The brain stem structures, the basal ganglia, the internal capsules, the cerebral hemispheric white matter and the cortex are best visualized on axial images. Optional techniques include axial or coronal T2 weighted fast spin echo or modular inversion recovery sequences. Whenever possible, the use of a high- resolution matrix is preferred. Depending on the findings, additional axial or coronal diffusion- weighted echo- planar sequences and an MR spectroscopic study may be indicated to enhance the sensitivity and diagnostic specificity. Very few diseases present with suggestive or pathognomonic abnormalities in the immediate postnatal period. The combination of conventional and diffusion- weighted MRI as well as MR spectroscopy may however lead to a more specific diagnosis. The short acquisition times (2. Diffusion- weighted MRI of the brain has already many well- established indications, including stroke and the assessment of normal and abnormal myelination. Analysis of the type and pattern of diffusion abnormalities may enhance the sensitivity and specificity of the MRI work- up in neonates. As the myelination process progresses, prominent diffusion anistrophy develops, characterized by relatively free water diffusion along the fiber tracts and restricted diffusion across the myelin sheaths. Isotropically restricted water diffusion presents with hypersignal on diffusion- weighted images. In vasogenic edema excess water moves into the extracellular space. As a result, the apparent tissue water diffusion increases, isotropically in the gray matter, and with a preferential direction along the fiber tracts in the white matter. Differentiation between them based on T1 or T2 relaxation properties is almost impossible. By demonstrating abnormal water shifts between the extra- and intracellular spaces and the resultant apparent water diffusion changes, DWI has the unique potential to differentiate between vasogenic and cytotoxic edema. Furthermore, different types and stages of myelin breakdown (dys- and demyelination) may also be identified based on water diffusion properties within the central nervous system. A specific form of brain edema (. Histopathologically, vacuolating myelinopathy is found in some of the neurometabolic diseases, such as Canavan’s disease, van der Knaap’s disease. MSUD. In vacuolating myelinopathy water is probably trapped within vacuoles between the myelin sheet layers, leading to isotropically restricted water diffusion. This explains the markedly increased signal intensities in areas of active vacuolating myelinopathy on diffusion- weighted images in MSUD (Fig. It is similar to the appearance in cytotoxic edema although the underlying pathological mechanisms are distinctly different (Fig. Additionally, this also allows clear differentiation between myelinated and non- myelinated structures in the neonatal brain, since in MSUD vacuolating myelinopathy presents with isotropically restricted water diffusion (hypersignal) and the non- myelinated white matter with diffusion abnormalities (hyposignal) suggestive of vasogenic edema. Hence, as a by- product, a very accurate in vivo myelination map is obtained (Fig.
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November 2017
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