Presentation
Abstract Two siblings are described who present with fumaric aciduria, a hitherto unreported organic aciduria. [ncbi.nlm.nih.gov]
Most IEMs present in a non specific manner. [alliedacademies.org]
Special emphasis is placed on acutely presenting disorders and emergency situations. The rationale of the approaches presented in this book are based on extensive, collective clinical experience. [books.google.de]
Three of the patients also carried a second, mitochondrial-related genetic alteration which was asymptomatically present in their healthy relatives. [hal.archives-ouvertes.fr]
Entire Body System
- Anemia
P74 ) Endocrine, nutritional and metabolic diseases E70-E88 2019 ICD-10-CM Range E70-E88 Metabolic disorders Type 1 Excludes androgen insensitivity syndrome ( E34.5- ) congenital adrenal hyperplasia ( E25.0 ) Ehlers-Danlos syndrome ( Q79.6 ) hemolytic anemias [icd10data.com]
Hematologic abnormalities are also found in classic organic acidurias including neutropenia, anemia, thrombocytopenia, or pancytopenia. [degruyter.com]
[…] deficiency AR 72 187 CD320 Methylmalonic aciduria due to transcobalamin receptor defect AR 1 CLPB 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN) AR 25 25 CTH Cystathioninuria AR 5 9 CUBN * Megaloblastic anemia [blueprintgenetics.com]
Dietary deficiency (seen in malnourished patients and vegetarians) as well as impaired absorption of B12 (pernicious anemia) are common causes. Management As with their presentation, the initial management of the organic acidemias is non-specific. [pedclerk.bsd.uchicago.edu]
Laboratory findings include megaloblastic anemia, homocystinuria, and hypomethioninemia. 29. The presence of megaloblastic anemia differentiates these defects from homocystinuria due to methylenetetrahydrofolate reductase deficiency Treatment [slideshare.net]
- Asymptomatic
Three of the patients also carried a second, mitochondrial-related genetic alteration which was asymptomatically present in their healthy relatives. [hal.archives-ouvertes.fr]
Glutaric aciduria type 1 has a variable presentation, but typically, affected neonates are asymptomatic in the first few months of life 3, other than developing macrocephaly. [radiopaedia.org]
As some of these organic acidemias are screened for in newborn testing, it is possible that an afflicted child may be identified while still in the asymptomatic period. [pedclerk.bsd.uchicago.edu]
Use of MRS to detect elevated glutamine and decreased myo-inositol brain levels was reported to identify symptomatic and asymptomatic subjects with partial OTCD[ 173, 174 ]. [doi.org]
- Weakness
MAL can cause an enlarged, weak heart (also called cardiomyopathy), so you may need to work with a cardiologist to monitor your child’s heart. [babysfirsttest.org]
Disorders Disease (OMIM Number) Defective Proteins or Enzymes Defective Gene or Genes (Chromosomal Location) Comments Hyperlysinemia (238700) Lysine: α -ketoglutarate reductase AASS (7q31.3)* Biochemical profile: Hyperlysinemia Clinical features: Muscle weakness [msdmanuals.com]
Lethargy, weak muscle tone, developmental delay, hepatomegaly, and poor eyesight are other MMA demonstrations. [ijp.mums.ac.ir]
Marked weakness and paralysis occur in about 30% of episodes, which may lead to respiratory failure requiring mechanical ventilation. Crises typically last 1-7 days but recuperation from paralytic crises can require weeks to months 25. Diagnosis [slideshare.net]
Patients with milder disease or heterozygous carriers for OTCD may develop specific weaknesses in several executive functions even if the IQ is normal. Regular testing for IQ, development and specific abilities/weaknesses is recommended. [doi.org]
- Fatigue
Its symptoms are a culmination similar to those of mitochondrial myopathy, chronic fatigue syndrome, fibromyalgia, dysautonomia, gastroparesis, POTS, and many more. My disorder is what is known as an organic aciduria. [themighty.com]
Gastrointestinal
- Vomiting
Vomiting, poor feeding, failure to thrive, lethargy, hypotonia, seizures, and developmental delay may occur in the first few months of life. Laboratory findings include megaloblastic anemia, homocystinuria, and hypomethioninemia. 29. The presence [slideshare.net]
INDICATIONS FOR TESTING: Symptoms of lethargy, coma, hypotonia, hypertonia, tachypnea, seizures, ataxia, vomiting, failure to thrive, developmental delay, hepatomegaly, and cytopenia can be due to abnormalities of organic acid metabolism. [research.njms.rutgers.edu]
A clinical presentation of a metabolic disorder, often first seen in infants who present with poor feeding, vomiting, tachypnea, acidosis, hyperammonemia, ketosis, ketonuria, irritability, and convulsions or hypotonia and lethargy, findings that are otherwise [journals.sbmu.ac.ir]
Twin siblings with a Reye's-like syndrome associated with abnormal organic aciduria. hypoglycaemia, diarrhoea and vomiting with close similarities to Jamaican vomiting sickness. Pediatr. Res. (1980b) (in press) Google Scholar Chalmers, R. [link.springer.com]
More typically, a few weeks or months after birth children start to experience vomiting, lethargy, poor feeding and hypotonia. An anion gap metabolic acidosis is usually present, however the blood pH can be normal or even alkalotic. [pedclerk.bsd.uchicago.edu]
- Failure to Thrive
Abstract We report a patient with a clinical picture consisting of small birth weight, connatal hypoplastic anaemia, vacuolised bone marrow precursors, failure to thrive, and, subsequently, by insulin-dependent diabetes, renal Fanconi syndrome, lactic [ncbi.nlm.nih.gov]
In a subgroup of the patients severe muscle hypotonia, central nervous system involvement and failure to thrive occur as well. [hal.archives-ouvertes.fr]
INDICATIONS FOR TESTING: Symptoms of lethargy, coma, hypotonia, hypertonia, tachypnea, seizures, ataxia, vomiting, failure to thrive, developmental delay, hepatomegaly, and cytopenia can be due to abnormalities of organic acid metabolism. [research.njms.rutgers.edu]
They manifested with developmental delay, failure to thrive and convulsions. History of consanguinity was present in three of them. [alliedacademies.org]
- Nausea
Anorexia and nausea/vomiting during the acute crisis period makes a significant oral intake unlikely. [newenglandconsortium.org]
Cardiovascular
- Hypertension
Most presented with neurological symptoms including cognitive decline, hypertensive encephalopathy, unsteady gait, myelopathy, and behavioral abnormalities. [emedicine.medscape.com]
Given the susceptibility of adults to develop intracranial hypertension and cerebral edema with hyperammonemia, dialysis should be started quickly, even before transfer to a specialised center, if ammonia exceeds 200 μmol/L. [doi.org]
Neurologic
- Seizure
myoclonus, apnea, death In infantile and episodic forms, seizures, intellectual disability, episodic delirium, chorea, vertical gaze palsy In late-onset form, progressive spastic diplegia, optic atrophy, but no cognitive impairment or seizures Treatment [msdmanuals.com]
Neurologic signs include seizures (approximately 25%), spasticity, hyperreflexia, and tremors. Diagnosis is through new born screening in developed countries. In developing countries identification of phenylketones in the urine by ferric chloride [slideshare.net]
Recognition of poor feeding, vomiting, dehydration, hypotonia, respiratory distress, and seizure may help in identifying ongoing metabolic decompensation. [emedicine.medscape.com]
INDICATIONS FOR TESTING: Symptoms of lethargy, coma, hypotonia, hypertonia, tachypnea, seizures, ataxia, vomiting, failure to thrive, developmental delay, hepatomegaly, and cytopenia can be due to abnormalities of organic acid metabolism. [research.njms.rutgers.edu]
In some cases, children with milder forms of disease may present later in infancy or within the first years of life with failure to thrive, seizures, abnormal behavior and eye-glazing. [pedclerk.bsd.uchicago.edu]
- Convulsions
The common clinical manifestations observed among all participants were neurological features like convulsions (25.7%), delayed milestones (17.9%), and followed by metabolic acidosis (17.2%) and hypoglycemia (10.1%). [biomedres.info]
They manifested with developmental delay, failure to thrive and convulsions. History of consanguinity was present in three of them. [alliedacademies.org]
A clinical presentation of a metabolic disorder, often first seen in infants who present with poor feeding, vomiting, tachypnea, acidosis, hyperammonemia, ketosis, ketonuria, irritability, and convulsions or hypotonia and lethargy, findings that are otherwise [journals.sbmu.ac.ir]
ISOVALERIC ACIDEMIA This condition is caused by the deficiency of the enzyme isovaleryl CoA dehydrogenase. Lethargy, convulsions, and coma may ensue in acute form. The characteristic odor of “sweaty feet” may be present (in body sweat and cerumen [slideshare.net]
Spurious elevations can be due to poor sample processing, tourniquet, crying, struggling or convulsions[ 166 ]. [doi.org]
Workup
Sclerosis for more information on these topics Differentials The following conditions should also be considered in the evaluation of cases of suspected methylmalonic acidemia: Diagnostic Tests Perform blood, imaging, and cardiac studies as part of the workup [emedicine.medscape.com]
[…] addition if >1000 ▪ Evaluate whether to continue specific treatment or to start palliative care ▪ Evaluate whether to aim at curative treatment or at palliative care ▪ Monitor phosphate levels and supplement early specially with hemodialysis The diagnostic workup [doi.org]
Serum
- Hyperammonemia
A possible explanation for hyperammonemia in propionic and methylmalonic aciduria. J Clin Invest. 1979, 64: 1544-1551. [ojrd.biomedcentral.com]
Thus, neonatal hyperammonemia can be due to UCDs, to other inborn errors that cause secondary hyperammonemia, to liver failure or to congenital infection. [doi.org]
Hence, the constellation of laboratory findings in MMA is the following: Metabolic acidosis with anion gap Ketonuria Hypoglycemia Hyperammonemia Hyperglycinemia The ketoacidosis, hyperammonemia and hypoglycemia can explain the lethargy and obtundation [newenglandconsortium.org]
Treatment
Therefore, the main aim of the treatment must be their removal by using standard treatment (high caloric, protein-free diet and carnitine). [ojrd.biomedcentral.com]
Additional treatments such as carnitine or insulin may prove to be useful. [ncbi.nlm.nih.gov]
TREATMENT OF CLASSIC PKU Principles of treatment of PKU Treatment must begin during first 7-10 days of life to prevent mental retardation.. Treatment aims at maintaining blood phenylalanine levels close to normal range. Treatment should be continued [slideshare.net]
Prognosis
Prognosis - Organic acidemia The prognosis of patients with organic acidemias varies with each disorder and usually depends on how quickly and accurately the condition is diagnosed and treated. [checkorphan.org]
These disorders vary in their prognosis, from manageable to fatal, and usually affect more than one organ system, especially the central nervous system. [humpath.com]
Many of the organic acidemias are detectable by newborn screening with tandem mass spectrometry.These disorders vary in their prognosis, from manageable to fatal, and usually affect more than one organ system, especially the central nervous system. [en.wikipedia.org]
In most instances, the disorders vary when it comes to the prognosis. Some patients may suffer from fatal or severe cases of the ailment, while others have manageable conditions. [organicacidemia.org]
Signal characteristics: T1: low signal T2/FLAIR: high signal GE/SWI: no susceptibility effect DWI: restricted diffusion acutely T1 C+ (Gd): no enhancement MR spectroscopy: lactate peak within basal ganglia acutely 6 Treatment and prognosis Glutaric aciduria [radiopaedia.org]
Etiology
In 183 short chapters, the book provides the essentials clinicians need on symptoms/signs, diagnostic tests, and neurologic disorders of all etiologies. For this edition, Timothy A. [books.google.de]
Our patients demonstrate that gastroenterologic disorders constitute a previously unrecognized etiology to be differentiated from inborn enzymatic errors associated with glutaric aciduria. [nature.com]
Etiology Most of the organic acidemias result from defective autosomal genes for various enzymes important to amino acid metabolism. Most are inherited as autosomal recessive diseases. [humpath.com]
We conclude that amino and organic acids in urine should be investigated in all children with progressive macrocephaly of unknown etiology to rule out glutaric aciduria type I. [analesdepediatria.org]
Early diagnosis and treatment may delay the progression of symptoms The more common etiologies of stroke are broadly classified as cardiac, infectious, hematologic, vascular, genetic, or metabolic. [emedicine.medscape.com]
Epidemiology
In Tunisia, no information is available on the incidence and epidemiological features of these diseases. [latunisiemedicale.com]
However, it is not yet a national policy in Thailand because of its cost and limited information about the epidemiology of IEM [ 19 ]. [degruyter.com]
Picca, Rome), liver transplantation (J. de Ville de Goyet, Rome), epidemiology (A. Tozzi, Rome) and ethics (C. Rehmann-Sutter, Basel) and a patient group representative (S. Hannigan, London). [doi.org]
Pathophysiology
It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. [zora.uzh.ch]
Kölker, Neurodegeneration and chronic renal failure in methylmalonic aciduria—A pathophysiological approach, Journal of Inherited Metabolic Disease, 31, 1, (35-43), (2007). M. Lindner, S. Ho, S. Kölker, G. Abdoh, G. F. Hoffmann and P. [doi.org]
The pathophysiology of these disorders is the result of toxicity of small molecules to brain, liver, kidney, pancreas, retina, and other organs. [web.archive.org]
Pathophysiology, diagnosis, and treatment of methylmalonic aciduria—recent advances and new challenges. Pediatric Nephrology. 2004;19(10):1071-4. 4. Karam PE, Habbal MZ, Mikati MA, Zaatari GE, Cortas NK, Daher RT. [ijp.mums.ac.ir]
Pathophysiology The metabolic precursor of methylmalonyl-CoA is propionyl-CoA, which is the product of the degradation of four essential amino acids, isoleucine, valine, methionine, and threonine as well as the degradation of odd-chain fatty acids and [newenglandconsortium.org]
Prevention
However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. [ncbi.nlm.nih.gov]
Conclusion: High index of suspicion from clinicians supported by preliminary screening tests can aid in early presumptive diagnosis, which helps in initiating early treatment to prevent lethal neurological complications. Author(s): Vidya S. [biomedres.info]
Treatment in the acute stage takes the form of prevention and correction of the catabolic state 1. In the chronic stage, a low protein diet with carnitine and riboflavin supplements should be given. [radiopaedia.org]