Propionic Acidemia Information for Health Professionals
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Hyperammonemia in Review: Pathophysiology, Diagnosis, and Treatment
Pediatr Nephrol DOI 10.1007/s00467-011-1838-5 EDUCATIONAL REVIEW Hyperammonemia in review: pathophysiology, diagnosis, and treatment Ari Auron & Patrick D. Brophy Received: 23 September 2010 /Revised: 9 January 2011 /Accepted: 12 January 2011 # IPNA 2011 Abstract Ammonia is an important source of nitrogen and is the breakdown and catabolism of dietary and bodily proteins, required for amino acid synthesis. It is also necessary for respectively. In healthy individuals, amino acids that are not normal acid-base balance. When present in high concentra- needed for protein synthesis are metabolized in various tions, ammonia is toxic. Endogenous ammonia intoxication chemical pathways, with the rest of the nitrogen waste being can occur when there is impaired capacity of the body to converted to urea. Ammonia is important for normal animal excrete nitrogenous waste, as seen with congenital enzymatic acid-base balance. During exercise, ammonia is produced in deficiencies. A variety of environmental causes and medica- skeletal muscle from deamination of adenosine monophos- tions may also lead to ammonia toxicity. Hyperammonemia phate and amino acid catabolism. In the brain, the latter refers to a clinical condition associated with elevated processes plus the activity of glutamate dehydrogenase ammonia levels manifested by a variety of symptoms and mediate ammonia production. After formation of ammonium signs, including significant central nervous system (CNS) from glutamine, α-ketoglutarate, a byproduct, may be abnormalities. Appropriate and timely management requires a degraded to produce two molecules of bicarbonate, which solid understanding of the fundamental pathophysiology, are then available to buffer acids produced by dietary sources. differential diagnosis, and treatment approaches available. -
Effect of Propionic Acid on Fatty Acid Oxidation and U Reagenesis
Pediat. Res. 10: 683- 686 (1976) Fatty degeneration propionic acid hyperammonemia propionic acidemia liver ureagenesls Effect of Propionic Acid on Fatty Acid Oxidation and U reagenesis ALLEN M. GLASGOW(23) AND H. PET ER C HASE UniversilY of Colorado Medical Celller, B. F. SlOlillsky LaboralOries , Denver, Colorado, USA Extract phosphate-buffered salin e, harvested with a brief treatment wi th tryps in- EDTA, washed twice with ph os ph ate-buffered saline, and Propionic acid significantly inhibited "CO z production from then suspended in ph os ph ate-buffe red saline (145 m M N a, 4.15 [I-"ejpalmitate at a concentration of 10 11 M in control fibroblasts m M K, 140 m M c/, 9.36 m M PO" pH 7.4) . I n mos t cases the cells and 100 11M in methyl malonic fibroblasts. This inhibition was we re incubated in 3 ml phosph ate-bu ffered sa lin e cont aining 0.5 similar to that produced by 4-pentenoic acid. Methylmalonic acid I1Ci ll-I4Cj palm it ate (19), final concentration approximately 3 11M also inhibited ' 'C0 2 production from [V 'ejpalmitate, but only at a added in 10 II I hexane. Increasing the amount of hexane to 100 II I concentration of I mM in control cells and 5 mM in methyl malonic did not impair palmit ate ox id ation. In two experiments (Fig. 3) the cells. fibroblasts were in cub ated in 3 ml calcium-free Krebs-Ringer Propionic acid (5 mM) also inhibited ureagenesis in rat liver phosphate buffer (2) co nt ain in g 5 g/ 100 ml essent iall y fatty ac id slices when ammonia was the substrate but not with aspartate and free bovine se rum albumin (20), I mM pa lm itate, and the same citrulline as substrates. -
Arginine-Provider-Fact-Sheet.Pdf
Arginine (Urea Cycle Disorder) Screening Fact Sheet for Health Care Providers Newborn Screening Program of the Oklahoma State Department of Health What is the differential diagnosis? Argininemia (arginase deficiency, hyperargininemia) What are the characteristics of argininemia? Disorders of arginine metabolism are included in a larger group of disorders, known as urea cycle disorders. Argininemia is an autosomal recessive inborn error of metabolism caused by a defect in the final step in the urea cycle. Most infants are born to parents who are both unknowingly asymptomatic carriers and have NO known history of a urea cycle disorder in their family. The incidence of all urea cycle disorders is estimated to be about 1:8,000 live births. The true incidence of argininemia is not known, but has been estimated between 1:350,000 and 1:1,000,000. Argininemia is usually asymptomatic in the neonatal period, although it can present with mild to moderate hyperammonemia. Untreated, argininemia usually progresses to severe spasticity, loss of ambulation, severe cognitive and intellectual disabilities and seizures Lifelong treatment includes a special diet, and special care during times of illness or stress. What is the screening methodology for argininemia? 1. An amino acid profile by Tandem Mass Spectrometry (MS/MS) is performed on each filter paper. 2. Arginine is the primary analyte. What is an in-range (normal) screen result for arginine? Arginine less than 100 mol/L is NOT consistent with argininemia. See Table 1. TABLE 1. In-range Arginine Newborn Screening Results What is an out-of-range (abnormal) screen for arginine? Arginine > 100 mol/L requires further testing. -
Summary Current Practices Report
18/10/2011 EU Tender “Evaluation of population newborn screening practices for rare disorders in Member States of the European Union” Short Executive Summary of the Report on the practices of newborn screening for rare disorders implemented in Member States of the European Union, Candidate, Potential Candidate and EFTA Countries Authors: Peter Burgard1, Martina Cornel2, Francesco Di Filippo4, Gisela Haege1, Georg F. Hoffmann1, Martin Lindner1, J. Gerard Loeber3, Tessel Rigter2, Kathrin Rupp1, 4 Domenica Taruscio4,Luciano Vittozzi , Stephanie Weinreich2 1 Department of Pediatrics , University Hospital - Heidelberg (DE) 2 VU University Medical Centre - Amsterdam (NL) 3 RIVM - Bilthoven (NL) 4 National Centre for Rare Diseases - Rome (IT) The opinions expressed in this document are those of the Contractor only and do not represent the official position of the Executive Agency for Health and Consumers. This work is funded by the European Union with a grant of Euro 399755 (Contract number 2009 62 06 of the Executive Agency for Health and Consumers) 1 18/10/2011 Abbreviations 3hmg 3-Hydroxy-3-methylglutaric aciduria 3mcc 3-Methylcrotonyl-CoA carboxylase deficiency/3-Methylglutacon aciduria/2-methyl-3-OH- butyric aciduria AAD Disorders of amino acid metabolism arg Argininemia asa Argininosuccinic aciduria bio Biotinidase deficiency bkt Beta-ketothiolase deficiency btha S, beta 0-thalassemia cah Congenital adrenal hyperplasia cf Cystic fibrosis ch Primary congenital hypothyroidism citI Citrullinemia type I citII Citrullinemia type II cpt I Carnitin -
Newborn Screening & Genetics
NEWBORN SCREENING ® 2 0 1 9 & GENETICS UNMET NEEDS • Funding for equipment, qualified staff and infrastructure changes to accommodate new testing • Funding for test development and validation • Quality assurance materials that reflect increased complexity of disease markers and address state’s expanding needs • Coordinated efforts nationwide in leading novel advances (e.g., next generation sequencing, electronic data exchange, etc.) in public health laboratories for newborn screening BACKGROUND NEWBORN SCREENING SAVES LIVES ACT Newborn screening (NBS) saves lives. Each year, over Recognizing the need for federal guidance and resources 12,000 newborn lives are changed because of the early to assist states in improving their NBS programs, detection and intervention NBS makes possible. NBS Congress enacted the Newborn Screening Saves Lives is one of the largest and most effective public health Act (P.L. 110-204) in 2008 and its reauthorization in interventions in the US, saving and improving the lives of 2014 (P.L. 113-240), ensuring: children, families and communities. • Enhanced state programs to provide screening, NBS is not a diagnostic test, but rather it determines counseling and healthcare services to newborns and a baby’s risk for certain genetic, metabolic, congenital children. and/or functional disorders. Abnormal screening results • Assistance in educating healthcare professionals cue healthcare providers to pursue additional diagnostic about screening and training in relevant new testing to determine if the baby has the disorder in technologies. question. If diagnosed early, these heritable conditions • Development and delivery of educational programs can be cured or successfully treated. about NBS counseling, testing, follow-up, treatment Almost all infants born in the US (about 98%) undergo and specialty services to parents, families and patient NBS, however, the number and types of disorders for advocacy and support groups. -
The Pharmabiotic for Phenylketonuria: Development of a Novel Therapeutic
University of South Carolina Scholar Commons Senior Theses Honors College Spring 2019 The hP armabiotic for Phenylketonuria: Development of a Novel Therapeutic Chloé Elizabeth LeBegue University of South Carolina, [email protected] Follow this and additional works at: https://scholarcommons.sc.edu/senior_theses Part of the Alternative and Complementary Medicine Commons, Amino Acids, Peptides, and Proteins Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Biotechnology Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Digestive, Oral, and Skin Physiology Commons, Digestive System Diseases Commons, Enzymes and Coenzymes Commons, Genetic Phenomena Commons, Medical Biotechnology Commons, Medical Genetics Commons, Medical Nutrition Commons, Medical Pharmacology Commons, Nutritional and Metabolic Diseases Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pharmaceutical Preparations Commons, Pharmaceutics and Drug Design Commons, and the Preventive Medicine Commons Recommended Citation LeBegue, Chloé Elizabeth, "The hP armabiotic for Phenylketonuria: Development of a Novel Therapeutic" (2019). Senior Theses. 267. https://scholarcommons.sc.edu/senior_theses/267 This Thesis is brought to you by the Honors College at Scholar Commons. It has been accepted for inclusion in Senior Theses by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. THE PHARMABIOTIC FOR PHENYLKETONURIA: DEVELOPMENT OF A NOVEL THERAPEUTIC By Chloé Elizabeth -
Fatal Propionic Acidemia: a Challenging Diagnosis
Issue: Ir Med J; Vol 112; No. 7; P980 Fatal Propionic Acidemia: A Challenging Diagnosis A. Fulmali, N. Goggin 1. Department of Paediatrics, NDDH, Barnstaple, UK 2. Department of Paediatrics, UHW, Waterford, Ireland Dear Sir, We present a two days old neonate with severe form of propionic acidemia with lethal outcome. Propionic acidemia is an AR disorder, presents in the early neonatal period with progressive encephalopathy and death can occur quickly. A term neonate admitted to NICU on day 2 with poor feeding, lethargy and dehydration. Parents are non- consanguineous and there was no significant family history. Prenatal care had been excellent. Delivery had been uneventful. No resuscitation required with good APGAR scores. Baby had poor suck, lethargy, hypotonia and had lost about 13% of the birth weight. Initial investigations showed hypoglycemia (2.3mmol/L), uremia (8.3mmol/L), hypernatremia (149 mmol/L), severe metabolic acidosis (pH 7.24, HCO3 9.5, BE -18.9) with high anion gap (41) and ketonuria (4+). Hematologic parameters, inflammatory markers and CSF examination were unremarkable. Baby received initial fluid resuscitation and commenced on IV antibiotics. Generalised seizures became eminent at 70 hours of age. Loading doses of phenobarbitone and phenytoin were given. Hepatomegaly of 4cm was spotted on day 4 of life. Very soon baby became encephalopathic requiring invasive ventilation. At this stage clinical features were concerning for metabolic disorder and hence was transferred to tertiary care centre where further investigations showed high ammonia level (1178 μg/dl) and urinary organic acids were suggestive of propionic acidemia. Specific treatment for hyperammonemia and propionic acidemia was started. -
Increased Citrulline Amino Aciduria/Urea Cycle Disorder
Newborn Screening ACT Sheet Increased Citrulline Amino Aciduria/Urea Cycle Disorder Differential Diagnosis: Citrullinemia I, argininosuccinic acidemia; citrullinemia II (citrin deficiency), pyruvate carboxylase deficiency. Condition Description: The urea cycle is the enzyme cycle whereby ammonia is converted to urea. In citrullinemia and in argininosuccinic acidemia, defects in ASA synthetase and lyase, respectively, in the urea cycle result in hyperammonemia and elevated citrulline. Medical Emergency: Take the Following IMMEDIATE Actions Contact family to inform them of the newborn screening result and ascertain clinical status (poor feeding, vomiting, lethargy, tachypnea). Immediately consult with pediatric metabolic specialist. (See attached list.) Evaluate the newborn (poor feeding, vomiting, lethargy, hypotonia, tachypnea, seizures and signs of liver disease). Measure blood ammonia. If any sign is present or infant is ill, initiate emergency treatment for hyperammonemia in consultation with metabolic specialist. Transport to hospital for further treatment in consultation with metabolic specialist. Initiate timely confirmatory/diagnostic testing and management, as recommended by specialist. Initial testing: Immediate plasma ammonia, plasma quantitative amino acids. Repeat newborn screen if second screen has not been done. Provide family with basic information about hyperammonemia. Report findings to newborn screening program. Diagnostic Evaluation: Plasma ammonia to determine presence of hyperammonemia. In citrullinemia, plasma amino -
Newborn Screening for X-ALD Can Happen Along with Routine Newborn Screening for Other Conditions in the First Few Days of Life
Newborn Screening for X-linked Adrenoleukodystrophy A Summary of the Evidence and Advisory Committee Decision Report Date: 14 October 2015 This summary was prepared under a contract to Duke University from the Maternal and Child Health Bureau of the Health and Resources and Services Administration (Contract Number: HHSH250201500002I/HHSH25034003T). EXECUTIVE SUMMARY This summary reviews the information the federal advisory committee used when deciding whether to recommend adding X-linked adrenoleukodystrophy (X-ALD) to the Recommended Uniform Screening Panel (RUSP) in 2015. About the condition X-ALD is a rare disorder caused by a change in a single human gene. Studies of patients with symptoms suggest that about 2-3 out of every 100,000 people have X-ALD. People with X-ALD do not have enough of a protein that helps the body break down certain types of fats. Babies with X-ALD look normal. There are different types of X-ALD that can cause problems with the adrenal glands, brain, and spinal cord. Without treatment, these problems can worsen quickly and cause death during childhood. X-ALD usually affects boys more severely than girls. Treatment for X-ALD There is no cure for X-ALD. Early diagnosis allows early monitoring and treatment for babies with X-ALD. Available treatments include cortisol replacement and human stem cell transplant. The treatment a patient needs depends on many factors, like the type of X-ALD. Detecting X-ALD in newborns Newborn screening for X-ALD can happen along with routine newborn screening for other conditions in the first few days of life. -
American Academy of Pediatrics Newborn Screening Task Force Recommendations: How Far Have We Come?
SUPPLEMENT ARTICLE American Academy of Pediatrics Newborn Screening Task Force Recommendations: How Far Have We Come? Michele A. Lloyd-Puryear, MD, PhDa, Thomas Tonniges, MD, FAAPb, Peter C. van Dyck, MD, MPH, FAAPa, Marie Y. Mann, MD, MPH, FAAPa, Amy Brin, MAb, Kay Johnson, MPHc, Merle McPherson, MD, FAAPa aHealth Resources and Services Administration, Rockville, Maryland; bAmerican Academy of Pediatrics, Elk Grove Village, Illinois; cJohnson Consulting Group, Hinesburg, Vermont The authors have indicated they have no financial relationships relevant to this article to disclose. ABSTRACT The partnership of the Health Resources and Services Administration (HRSA)/ Maternal and Child Health Bureau (MCHB) and the American Academy of Pedi- atrics (AAP) for improving health care for all children has long been recognized. In www.pediatrics.org/cgi/doi/10.1542/ peds.2005-2633B 1998, the establishment of the Newborn Screening Task Force marked a major doi:10.1542/peds.2005-2633B initiative in addressing the needs of the newborn screening system. At the request Dr Tonniges’ current affiliation is Boystown of HRSA/MCHB, the AAP convened the task force to ensure that pediatric clini- Institute for Child Health Improvement, cians assumed a leadership role in examining the totality of the newborn screening Omaha, NE; Ms Brin is currently enrolled in the School of Nursing, Vanderbilt University system, including the necessary linkage to medical homes. The task force’s report, Key Words published in 2000, outlined major recommendations for federal, state, and other newborn screening, medical home, system national partners in addressing the identified barriers and needed enhancements integration, federal initiatives, newborn of the care delivery system. -
Newborn Screening FACT SHEET
Newborn Screening FACT SHEET What is newborn screening? Blood spot screening checks babies for: Arginemia Newborn screening is a set of tests that check babies Argininosuccinate acidemia for serious, rare disorders. Most of these disorders Beta ketothiolase deficiency cannot be seen at birth but can be treated or helped Biopterin cofactor defects (2 types) if found early. The three tests include blood spot, Biotinidase deficiency hearing, and pulse oximetry screening. Carnitine acylcarnitine translocase deficiency Carnitine palmitoyltransferase deficiency (2 types) Carnitine uptake defect Citrullinemia (2 types) Blood spot screening checks for over Congenital adrenal hyperplasia 50 rare but treatable disorders. Early Congenital hypothyroidism Cystic fibrosis detection can help prevent serious health Dienoyl-CoA reductase deficiency problems, disability, and even death. Galactokinase deficiency The box on the right lists the disorders Galactoepimerase deficiency screened for in Minnesota. Galactosemia Glutaric acidemia (2 types) Hearing screening checks for hearing Hemoglobinopathy variants loss in the range where speech is heard. Homocystinuria Hypermethioninemia Identifying hearing loss early helps babies Hyperphenylalaninemia stay on track with speech, language, and Isobutyryl-CoA dehydrogenase deficiency communication skills. Isovaleric acidemia Long-chain hydroxyacyl-CoA dehydrogenase deficiency Pulse oximetry screening checks for a set Malonic acidemia of serious, life-threatening heart defects Maple syrup urine disease known as -
Newborn Screening for Propionic Acidaemia External Review Against Programme Appraisal Criteria for the UK National Screening Committee (UK NSC)
Newborn screening for propionic acidaemia External review against programme appraisal criteria for the UK National Screening Committee (UK NSC) Version: 1 Bazian Ltd. May 2015 This analysis has been produced by Bazian Ltd for the UK National Screening Committee. Bazian Ltd has taken care in the preparation of this report, but makes no warranty as to its accuracy and will not be liable to any person relying on or using it for any purpose. The UK NSC advises Ministers and the NHS in all four UK countries about all aspects of screening policy. Its policies are reviewed on a 3 yearly cycle. Current policies can be found in the policy database at http://www.screening.nhs.uk/policies and the policy review process is described in detail at http://www.screening.nhs.uk/policyreview Template v1.2, June 2010 UK NSC External Review Abbreviations List Abbreviation Meaning C0 Free carnitine C2 Acetylcarnitine (Number indicates the number of carbon atoms in acyl chain attached to carnitine) C3 Propionylcarnitine C4 Butyrylcarnintine C16 Hexadecanoylcarnitine C4DC Methylmalonyl/succinyl-carnitine CblA Cobalamin deficiency type A. Form of MMA caused by mutation in the MMAA gene CblB Cobalamin deficiency type B. Form of MMA caused by mutation in the MMAB gene CblC Cobalamin deficiency type C. Form of MMA caused by mutation in the MMACHC gene CblD Cobalamin deficiency type D. Form of MMA caused by mutation in the MMADHC gene Gly Glycine HCSD Holocarboxylase synthetase deficiency Met Methionine MCD Multiple carboxylase deficiency (includes HCSD and biotinidase deficiency ) MMA Methylmalonic acidaemia/aciduria MMAA Methylmalonic aciduria (cobalamin deficiency) cblA type gene MMAB Methylmalonic aciduria (cobalamin deficiency) cblB type gene MMACHC Methylmalonic aciduria (cobalamin deficiency) cblC type with homocysteinuria gene MMADHC Methylmalonic aciduria (cobalamin deficiency) cblD type with homocysteinuria gene MUT Methylmalonyl CoA mutase gene PA Propionic acidaemia/aciduria R4S Region 4 Stork RC Reviewer calculated figure (i.e.