Materiały źródłowe

• #1 MCAD deficiency – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mcad-deficiency/symptoms-causes/syc-20353745

  MCAD deficiency is present from birth and is a lifelong condition. […] In the United States, all states test for MCAD deficiency at birth as part of newborn screening. […] If MCAD deficiency is diagnosed and treated early, the disorder can be well managed through diet and lifestyle. […] In the United States and many other countries, newborn screening programs test for MCAD deficiency. […] After your first evaluation, you may be referred to a specialist in evaluating and treating MCAD deficiency. […] MCAD deficiency is caused by a change in the ACADM gene. […] The condition is inherited from both parents in an autosomal recessive pattern. […] If you inherit only one changed gene, you won’t develop MCAD deficiency. […] A child is at risk of MCAD deficiency if both parents are carriers of a gene known to cause it. […] If metabolic crisis caused by MCAD deficiency is left untreated, it can lead to seizures, liver problems, brain damage, coma, and sudden death.

• #1 MCAD deficiency – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mcad-deficiency/diagnosis-treatment/drc-20353747

  MCAD deficiency is diagnosed through newborn screening followed by genetic testing. […] Many countries, including all states in the United States, screen for MCAD deficiency at birth. Using a heel prick, a few drops of your baby’s blood are taken and analyzed. If screening levels are outside the standard range, additional testing can be done. […] Genetic testing can reveal the changed gene that causes MCAD deficiency. Depending on the type of test, a sample of blood or saliva or cells from the inside of the cheek, the skin or other tissue is collected and sent to a lab to be tested. Your health care provider may also recommend testing family members for this gene. Genetic counseling can help you understand the testing process and what the results mean.

• #1

  https://www.gov.uk/government/publications/mcadd-suspected-description-in-brief/mcadd-detailed-information

  This information is for parents if their baby is suspected of having MCADD or has been diagnosed with MCADD following their newborn blood spot screening test (heel prick test). It will help you and your healthcare professionals to talk through the next stages of your babys care. […] When your baby was about 5 days old, your midwife took some blood from your babys heel for their newborn blood spot screening test (the heel prick test). The newborn blood spot screening test measures the amount of a substance called octanoylcarnitine (C8) in the blood. A high level of octanoylcarnitine (C8) suggests your baby may have MCADD. This is called a screen positive result. […] If your baby has a screen positive result, you will be seen by a metabolic doctor, dietitian and nurse specialist (the metabolic team). The team will provide advice and support. Blood and urine tests will be carried out to confirm if your baby has MCADD.

• #1 Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1424/

  Individuals with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency typically appear normal at birth, and many are diagnosed through newborn screening programs. […] The diagnosis of MCAD deficiency is established in a proband through biochemical testing (prominent accumulation of C8-acylcarnitine (octanoylcarnitine) with lesser elevations of C6-, C10-, and C10:1-acylcarnitines and elevated C8/C2 and C8/C10 ratios) AND/OR by identification of biallelic pathogenic variants in ACADM by molecular genetic testing OR by significantly reduced activity of MCAD activity in blood or cultured skin fibroblasts. […] Because of its relatively high sensitivity, ACADM molecular genetic testing can obviate the need for enzymatic testing, which is available only in limited academic centers. […] The diagnosis of MCAD deficiency is established in a proband by confirmatory biochemical testing AND/OR by identification of biallelic pathogenic (or likely pathogenic) variants in ACADM by molecular genetic testing OR by significantly reduced medium-chain acyl-CoA dehydrogenase enzyme activity in blood or cultured skin fibroblasts. […] Biochemical and molecular diagnostic methods for MCAD deficiency are sensitive enough to identify asymptomatic affected individuals without using provocative tests. […] Confirmatory postmortem testing is possible in the individual with sudden and unexpected death if MCAD deficiency is suspected.

• #1

  https://gmdi.org/Resources/Nutrition-Guidelines/MCAD

  Medium chain acyl CoA dehydrogenase deficiency (MCADD) is caused by mutations in the medium chain acyl CoA dehydrogenase (MCAD) gene leading to insufficient enzymatic activity to allow complete mitochondrial beta oxidation of fatty acids. […] It is possible to detect MCADD through tandem mass spectrometry newborn screening of blood spots. […] For any positive screen, further confirmatory testing is necessary before a diagnosis of MCADD can be made. […] A repeat newborn screen, in and of itself, is not sufficient for confirmatory testing for MCADD. […] The primary intervention goal for MCADD individuals is to avoid situations in which the cells must rely solely on stored fats for energy (i.e., avoid fasting). […] The intervention strategies for illness should be the most emphasized aspect of counseling for the MCADD individual and his caretakers.

• #1 Medium-chain acyl-CoA dehydrogenase deficiency – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/medium-chain-acyl-coa-dehydrogenase-deficiency/

  Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder of fatty acid oxidation that prevents the conversion of fats to energy via hepatic ketogenesis. This impairs the supply of energy to peripheral tissues, causing a continual reliance on glucose to provide energy. […] In MCADD, plasma acylcarnitine analysis has a characteristic abnormal pattern of increased C6 to C10 acylcarnitine species; C8 is usually especially elevated. This can be detected by tandem mass-spectrometry performed on dried blood spots, which is used as part of the newborn blood spot screening programme in England to diagnose MCADD. However, acylcarnitine analysis can also be performed on plasma if investigations are required in older patients. […] Urine organic acid and urine acylglycine analyses are also used in diagnosis. In MCADD, these tests demonstrate elevated C6 to C10 dicarboxylic acids, elevated hexanoylglycine and elevated suberylglycine.

• #1 Medium‐chain Acyl‐COA dehydrogenase deficiency: Pathogenesis, diagnosis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9836253/

  Medium chain length acylcarnitines, specifically octanoylcarnitine (C8) and decanoylcarnitine (C10) are measured on newborn screening blood spot cards using tandem mass spectrometry. […] Infants who display abnormally high levels of C8 or C10 should be referred to secondary treatment centers for definitive diagnosis or further genetic screening. […] Liquid chromatography tandem mass spectrometry is the standard method for diagnosis of MCADD. […] While NBS using dried blood samples has been successful in its identification of affected children, there is concern over its associated false positivity rate; LCMS/MS has been suggested as an additional or alternative test to blood spot analysis to reduce the incidence of false-positive tests. […] Asymptomatic individuals may show normal acylcarnitine levels using tandem mass spectrometry, and therefore require urine acylglycine assays to demonstrate elevated n-hexanoylglycine (HG), 3-phenylpropionylglycine, octanoylglycine (OG) and suberylglycine (SG).

• #1 Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency Full Gene Analysis, Varies – Covenant HealthCare Laboratory Test Directory

  https://covenantlab.testcatalog.org/show/MCADZ

  Confirmation of diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (as a follow-up to biochemical analyses) […] Diagnosis of MCAD deficiency in autopsy specimens […] Review of clinical features and biochemical analysis via plasma acylcarnitines (ACRN / Acylcarnitines, Quantitative, Plasma), fatty acid profile (FAO / Fatty Acid Oxidation Probe Assay, Fibroblast Culture), urine organic acids (OAU / Organic Acids Screen, Random, Urine), and urine acylglycines (ACYLG / Acylglycines, Quantitative, Urine) are always recommended as the initial evaluation for MCAD. […] The MCAD gene (ACADM) maps to 1p31 and has 12 exons, spanning 44 kb of DNA. Most variants are family-specific with the exception of the recurrent A->G transition at nucleotide 985 (985A->G). Among MCAD-deficient patients, approximately 52% are homozygous for the 985A->G pathogenic variant. The majority of the remaining patients are compound heterozygous for the 985A->G pathogenic variant and a different pathogenic variant.

• #1 Medium Chain Acyl-CoA Dehydrogenase (MCAD) Gene Sequencing | Test Detail | Quest Diagnostics

  https://testdirectory.questdiagnostics.com/test/test-detail/91284/medium-chain-acyl-coa-dehydrogenase-mcad-gene-sequencing?p=r&cc=MASTER

  Medium Chain Acyl-CoA Dehydrogenase (MCAD) Gene Sequencing – Based upon newborn screening results, approximately 50% of affected individuals are homozygous for the common variant, p.Lys304Glu (K304E, c.985A>G)K304E, and approximately 40% are compound heterozygous for p.Lys304Glu (K304E, c.985A>G)K304E and one of the more than 40 other, previously described, rare alleles. Nucleotide sequence analysis can be used to detect these rare alleles and can also be used to detect novel, deleterious variants. Therefore, nucleotide sequence analysis can be used for confirmatory diagnosis detection. In addition, it can be used for carrier testing and prenatal diagnosis. […] This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

• #1 Medium‐chain Acyl‐COA dehydrogenase deficiency: Pathogenesis, diagnosis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9836253/

  Death in the first manifestation of MCADD for previously undiagnosed individuals has been reported in between 18 and 25% of cases. […] In these cases, results of urinalysis or NBS may not have been used to conclusively diagnose MCADD as an underlying cause of metabolic decompensation and as such autopsy may provide certainty to a cause of death.

• #1 Medium-chain acyl-CoA dehydrogenase deficiency: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/medium-chain-acyl-coa-dehydrogenase-deficiency/

  Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). […] Signs and symptoms of MCAD deficiency typically appear during infancy or early childhood and can include vomiting, lack of energy (lethargy), and low blood glucose (hypoglycemia). […] In rare cases, symptoms of this disorder are not recognized early in life, and the condition is not diagnosed until adulthood. […] People with MCAD deficiency are at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death. […] Problems related to MCAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections.

• #1 Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-102

  The main goal of the present study was to evaluate any relationships between biochemical findings at diagnosis, genotype, free carnitine (C0) levels during follow-up, and clinical outcome, in patients with MCADD detected by NBS. […] A diagnosis of MCADD was confirmed by molecular testing in all patients; 34 patients were homozygous for the prevalent c.985AG (p.Lys329Glu) mutation and 10 patients were compound heterozygous for the prevalent and another mutation. […] Levels of C8 and ratios of C8/C10 and C8/C2 were significantly higher (p=0.016), while C0 was significantly lower (p0.001) in patients who were homozygous for the prevalent c.985AG mutation, compared to with those with other genotypes. […] Following carnitine treatment, the average C0 levels were significantly lower in patients homozygous for the common mutation than in patients with other mutations (14 mol/L vs 22 mol/L, p0.001).

• #1 Medium-chain acyl-CoA dehydrogenase deficiency: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/medium-chain-acyl-coa-dehydrogenase-deficiency/

  In the United States, the estimated incidence of MCAD deficiency is 1 in 17,000 people. […] Mutations in the ACADM gene cause MCAD deficiency. […] This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. […] The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. […] Genetic Testing Registry: Medium-chain acyl-coenzyme A dehydrogenase deficiency. […] Newborn screening for medium chain acyl-CoA dehydrogenase deficiency: evaluating the effects on outcome.

• #1 MCADD — New England Consortium of Metabolic Programs

  https://www.newenglandconsortium.org/mcadd-1

  If your babys newborn screening result showed a C8 level 2 mol/L, he or she probably has MCADD. If the result was 1-2 mol/L your baby either could still have MCADD or it may have been a false positive result. The newborn screening test will be repeated and additional tests will be undertaken to help determine if your baby has MCADD or not. Typically the results of these tests take up to 4 days to come back. Depending on the test results, additional testing can take a variable amount of time to confirm the diagnosis. In a very small minority of cases, it can be difficult to determine whether a child is affected or not. […] As MCADD is an inherited condition it is essential to have your other children tested. Children from the same father and mother as the affected infant have a 1 in 4 (25%) chance of having MCADD. Your other children can appear healthy and still have MCADD. If they have MCADD, successfully having weathered illnesses in the past is no guarantee that an illness in the future will not have serious consequences. Since there is a risk for having a future child with MCADD it is important to let your obstetrician and pediatrician know that you have a child with MCADD if you are planning future pregnancies so that they may discuss the options with you and prepare accordingly.

• #1 RFTS – Home Page

  https://www.wvdhhr.org/nbms/diseases/Medium_Chain_Acyl_CoA_Dehydrogenase.asp

  Genotype/phenotype correlation is not straightforward, and the treatment of individuals with milder mutations remains controversial. There are questions yet to be answered, such as whether some (or all) individuals with the less deleterious mutations (either in combination with the common 985 mutation or in combinations with one another) who have a biochemical phenotype would ever have medical problems. In addition, would some such individuals have serious episodes and others would not because of unknown modifying factors? Until we know the answer to these and other questions, we would be remiss in not treating everyone identified, perhaps overtreating some individuals. Newborn screening for MCAD deficiency will be key in answering some of these questions.

• #1 SciELO Brazil – The value of fasting in the diagnosis of medium-chain acyl-CoA dehydrogenase deficiency The value of fasting in the diagnosis of medium-chain acyl-CoA dehydrogenase deficiency

  https://www.scielo.br/j/jbpml/a/5XncHP8LCqMFg3v94csrgQC/

  Female patient carrier of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) with recurrent clinical episodes of hypoglycemia and altered level of consciousness, presented changes in blood acylcarnitine profile by tandem mass spectrometry and in the urinary organic acid analysis by gas chromatography/mass spectrometry (GC/MS). […] This case demonstrates the importance of fasting prior biological sample collection (when possible) when MCADD is suspected, and emphasizes that the time/momentum of biological sample collection is crucial to diagnosis, considering the possibility that MCADD is underdiagnosed in Brazil. […] In a condition suggestive of MCADD, a differential diagnosis is necessary, as this condition presents clinical signs common to other beta-oxidation disorders. […] The MCADD diagnosis requires considering patients clinical status (asymptomatic or symptomatic) at the of biological sample collection momentum.

• #1 Untargeted Metabolomics Identifies Biomarkers for MCADD Neonates in Dried Blood Spots

  https://www.mdpi.com/1422-0067/24/11/9657

  Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is clinically diagnosed using Newborn Bloodspot Screening (NBS) and genetic testing. […] However, the NBS programs’ efficiency in detecting IMDs, including MCADD, shows drawbacks concerning clinical diagnosis. […] Thus, a study suggested utilizing the genetic sequencing of DBS from false-positive-diagnosed MCADD patients as a validation method for the diagnosed patients. […] Therefore, the positive NBS results for MCADD are confirmed using molecular genetic testing, such as whole or exosome sequencing, which detects mutations in the ACADM gene. […] Based on these drawbacks associated with the NBS program and genetic approaches, there have been demands in the clinical field to identify other alternative and complementary diagnostic approaches for MCADD.

• #1 The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: An update | Genetics in Medicine

  https://www.nature.com/articles/gim200638

  The most common fatty acid oxidation disorder, medium chain acyl-CoA dehydrogenase deficiency (MCADD), has become the focal point for the adoption of tandem mass spectrometry to detect it and related inborn errors of metabolism. […] Currently available information from screening studies on the frequency of detection of MCADD in newborns, as well as the frequency of homozygotes for the common mutation in the ACADM gene, is summarized. […] In addition, a systematic review was undertaken of the published literature on the frequency of mortality and developmental disabilities among children with MCADD, both in screened and unscreened cohorts. […] It seems that in the absence of newborn screening for MCADD, premature death or serious disability occurs in 20% to 25% of children with the disorder.

• #1 The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: An update | Genetics in Medicine

  https://www.nature.com/articles/gim200638

  The frequency of deaths among older siblings of children with MCADD seems elevated relative to that among probands. […] Newborn screening for MCADD clearly prevents death and disability in many children with the disorder. […] We conservatively project that one in six children born with MCADD will die in childhood in the absence of screening. […] Without early asymptomatic detection, at least half of children with MCADD will experience a metabolic crisis, and up to 1 in 10 survivors will develop a serious developmental disability. […] Conservatively, between one in five and one in four children with MCADD will experience death or severe disability without newborn screening for the disorder.

• #1 MCAD Deficiency

  https://my.clevelandclinic.org/health/diseases/21973-mcad-deficiency

  Treatment for MCAD deficiency focuses on meeting nutritional requirements for your childs body and reducing long periods of time between meals, which may trigger symptoms of the condition. […] There’s no way to prevent MCAD deficiency because it’s a genetic condition that passes from parents to children. […] Early diagnosis and treatment of MCAD deficiency significantly improve your babys quality of life, and offer a good prognosis. […] The majority of people diagnosed with MCAD deficiency live normal and healthy lives. […] The best way to take care of your child with MCAD deficiency is to minimize long periods when they go without eating by scheduling meals closer together and more frequently.

• #1

  http://www.idph.state.il.us/healthwellness/fs/mcad.htm

  All of these disorders are inherited in an autosomal recessive pattern. […] Parents should understand that treatment is lifelong and that compliance with dietary management and awareness of and prompt attention to episode triggers, including illness and fasting, are imperative to the child’s health, growth and development. […] Infants and children with a fatty acid oxidation defect should have regular follow-up appointments with a metabolic disease specialist. […] Parents should be warned that if an infant shows warning signs of the disorder, such as lethargy or vomiting, they should immediately seek medical attention.

• #1

  https://www.gov.uk/government/publications/mcadd-suspected-description-in-brief/mcadd-suspected

  MCADD becomes a problem during prolonged fasting and illness because fat cannot be broken down quickly enough and harmful substances build up. […] If your baby has a screen positive result, you will be seen by a metabolic doctor, dietitian and nurse specialist (the metabolic team). The team will provide advice and support. Blood and urine tests will be carried out to confirm if your baby has MCADD. […] If your baby does have MCADD, the metabolic team will explain the condition in more detail and answer any questions you might have. They will teach you how to look after your child during illness, and they will arrange regular follow-up appointments. Following their advice on illness management is very important for your baby’s health.

• #1 Newborn screening information for medium-chain acyl-CoA dehydrogenase deficiency | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency

  Children who receive early treatment for medium-chain acyl-CoA dehydrogenase deficiency (MCAD) have healthy growth and development. […] If MCAD is not treated, children may experience breathing problems, seizures, liver troubles, brain damage, coma, and possibly death. Early screening and treatment can avoid these effects. […] Because MCAD is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for MCAD, and understand what this diagnosis means for other family members and future pregnancies.

• #2 MCAD Deficiency

  https://my.clevelandclinic.org/health/diseases/21973-mcad-deficiency

  MCAD deficiency is a genetic condition when your body can’t convert certain fats into energy. […] MCAD deficiency is a condition that prevents your body from turning fats into energy. […] MCAD deficiency is a genetic condition that you inherit when both of your parents carry a copy of the mutated ACADM gene, and you inherit the mutated copy from each of your parents (autosomal recessive). […] MCAD deficiency occurs in about 1 out of every 15,000 individuals. […] MCAD deficiency is a condition your healthcare provider will test for during a newborn screening, which means a diagnosis is possible before your baby shows any symptoms of the condition. […] Your healthcare provider might order additional tests, including genetic testing, where they will take a small sample of your babys blood, urine or tissue to verify the diagnosis.

• #2 MCAD deficiency – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mcad-deficiency/symptoms-causes/syc-20353745

  MCAD deficiency is present from birth and is a lifelong condition. […] In the United States, all states test for MCAD deficiency at birth as part of newborn screening. […] If MCAD deficiency is diagnosed and treated early, the disorder can be well managed through diet and lifestyle. […] In the United States and many other countries, newborn screening programs test for MCAD deficiency. […] After your first evaluation, you may be referred to a specialist in evaluating and treating MCAD deficiency. […] MCAD deficiency is caused by a change in the ACADM gene. […] The condition is inherited from both parents in an autosomal recessive pattern. […] If you inherit only one changed gene, you won’t develop MCAD deficiency. […] A child is at risk of MCAD deficiency if both parents are carriers of a gene known to cause it. […] If metabolic crisis caused by MCAD deficiency is left untreated, it can lead to seizures, liver problems, brain damage, coma, and sudden death.

• #2 MCADD

  https://www.nhs.uk/conditions/mcadd/

  MCADD is a lifelong condition that’s present from birth. It is usually picked up using the newborn blood spot test. […] A newborn blood spot test is now offered to all babies in England to earlier help detect problems including MCADD. […] If your baby has a screen positive result, further urine and blood tests will be carried out to confirm the diagnosis.

• #2 Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

  https://www.wadsworth.org/node/2638/printable/print

  MCAD deficiency is inherited in an autosomal recessive pattern. […] Screening for MCAD deficiency is accomplished by measuring acylcarnitines (C6 and C8) by tandem mass spectrometry (MS/MS). […] If an elevation of C8 is identified, DNA testing is performed for a single common mutation, p.K329E. […] Diagnostic testing includes quantification of plasma acylcarnitines, urine organic acids, and urine acylglycines. Molecular genetic testing of the ACADM gene may be used for confirmation of the diagnosis.

• #2

  https://portal.ct.gov/Newborn-Screening-Program/Disorders/MCADD

  You have just heard that your baby may have MCADD. Please understand that the newborn screening is just that—a screening test. Further testing is needed to confirm or rule out the diagnosis. […] Newborn screening is not the same as diagnostic testing. A diagnostic test can tell with more certainty whether or not a child has a condition. On the other hand, a screening test simply indicates that a child may have a condition. The purpose of a screening test is to find babies that should have diagnostic testing. […] Most babies who have follow up testing for MCADD are healthy, and will not have MCADD. However, out of range screening results CAN indicate a disorder, so it is important to follow your doctors advice get your baby tested quickly so that final results can be confirmed. […] If further testing finds that your baby has MCADD, they will meet with a geneticist and dietician to discuss MCADD in more detail and to go over questions that you might have. A specialist may recommend medication, supplements, or frequent feedings. This will help to prevent health problems. Children with MCADD can have healthy growth and development. […] If untreated, MCADD can cause medical problems. However, if the condition is found and treated early, individuals with MCADD can often lead healthy lives.

• #2 Medium-chain Acyl-CoA Dehydrogenase (MCAD) Deficiency | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/medium-chain-acyl-coa-dehydrogenase-mcad-deficiency

  MCAD deficiency is a genetic disorder caused by changes in the ACADM gene. […] Diagnosis of MCAD deficiency is typically established in those who have: […] Characteristic molecular patterns on plasma acylcarnitine tests and urine organic acid analysis […] Pathogenic genetic variants identified through genetic sequencing.

• #2 Medium‐chain Acyl‐COA dehydrogenase deficiency: Pathogenesis, diagnosis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9836253/

  Medium chain length acylcarnitines, specifically octanoylcarnitine (C8) and decanoylcarnitine (C10) are measured on newborn screening blood spot cards using tandem mass spectrometry. […] Infants who display abnormally high levels of C8 or C10 should be referred to secondary treatment centers for definitive diagnosis or further genetic screening. […] Liquid chromatography tandem mass spectrometry is the standard method for diagnosis of MCADD. […] While NBS using dried blood samples has been successful in its identification of affected children, there is concern over its associated false positivity rate; LCMS/MS has been suggested as an additional or alternative test to blood spot analysis to reduce the incidence of false-positive tests. […] Asymptomatic individuals may show normal acylcarnitine levels using tandem mass spectrometry, and therefore require urine acylglycine assays to demonstrate elevated n-hexanoylglycine (HG), 3-phenylpropionylglycine, octanoylglycine (OG) and suberylglycine (SG).

• #2 Diagnosis and Discussion – Case 1076 | Department of Pathology

  https://www.path.pitt.edu/diagnosis-and-discussion-case-1076

  Urine organic acid and urine acyl glycine analysis can also provide supportive evidence of MCADD deficiency. […] Increased levels of hexanoylglycine (C6), octanoylglycine (C8), decanoylglycine (C10) along with low ketone are usual pattern on urine organic acid analysis. […] The parents of an affected child are carriers of at least one ACADM pathogenic variant. […] However, with the broad application of newborn screening, this is no longer necessary.

• #2 MCADZ – Overview: Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency Full Gene Analysis, Varies

  https://www.mayocliniclabs.com/test-catalog/overview/35478

  The MCAD gene (ACADM) maps to 1p31 and has 12 exons, spanning 44 kb of DNA. […] A small percentage of individuals who are carriers or have a diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency may have a variant that is not identified by this method (eg, large genomic deletions, promoter variants). […] Test results should be interpreted in the context of clinical findings, family history, and other laboratory data.

• #2 MCADD – Genetics

  https://www.uab.edu/medicine/genetics/medical-genomics-laboratory/testing-services/mcadd

  Candidates for Testing: Patients seeking confirmation of diagnosis for individuals with an abnormal acylcarnitine profile, hypoglycemic episodes, lethargy, seizures or a family history of MCADD. […] For ACADM testing, we distinguish 2 types of test requests: targeted variant analysis of the c.985AG, p.K329E variant (MCD2 testing) and comprehensive sequence analysis of the ACADM gene (MCD1 testing). MCD2 is the priority test for the MCADD patients, since the common variant p.K329E in exon 11 of ACADM gene accounts for 80-90% of the variant alleles. If the patient is heterozygous for p.K329E or does not carry this most frequent variant, the comprehensive ACADM variant analysis (MCD1 testing) is performed.

• #2 Medium Chain Acyl-CoA Dehydrogenase (MCAD) Gene Sequencing | Test Detail | Quest Diagnostics

  https://testdirectory.questdiagnostics.com/test/test-detail/91284/medium-chain-acyl-coa-dehydrogenase-mcad-gene-sequencing?p=r&cc=MASTER

  Medium Chain Acyl-CoA Dehydrogenase (MCAD) Gene Sequencing – Based upon newborn screening results, approximately 50% of affected individuals are homozygous for the common variant, p.Lys304Glu (K304E, c.985A>G)K304E, and approximately 40% are compound heterozygous for p.Lys304Glu (K304E, c.985A>G)K304E and one of the more than 40 other, previously described, rare alleles. Nucleotide sequence analysis can be used to detect these rare alleles and can also be used to detect novel, deleterious variants. Therefore, nucleotide sequence analysis can be used for confirmatory diagnosis detection. In addition, it can be used for carrier testing and prenatal diagnosis. […] This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

• #2 MCADD (medium chain acyl-CoA dehydrogenase deficiency) – newbornscreening.info

  https://www.newbornscreening.info/mcadd-medium-chain-acyl-coa-dehydrogenase-deficiency/

  If both gene changes have been found in your child with MCADD, DNA testing can be done during future pregnancies. […] Brothers and sisters can be tested for MCADD using DNA testing or other special tests. […] About one in every 15,000 babies in the United States is born with MCADD. […] MCADD happens more often in white people from Northern Europe and the United States.

• #2 Medium-chain acyl-coenzyme A dehydrogenase deficiency – Wikipedia

  https://en.wikipedia.org/wiki/Medium-chain_acyl-coenzyme_A_dehydrogenase_deficiency

  Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation that impairs the body’s ability to break down medium-chain fatty acids into acetyl-CoA. […] Prior to expanded newborn screening, MCADD was an underdiagnosed cause of sudden death in infants. […] Clinically, MCADD or another fatty acid oxidation disorder is suspected in individuals who present with lethargy, seizures, coma and hypoketotic hypoglycemia, particularly if triggered by a minor illness. […] In areas with expanded newborn screening using tandem mass spectrometry (MS/MS), MCADD is usually detected shortly after birth, by the analysis of blood spots collected on filter paper. […] After biochemical suspicion of MCADD, molecular genetic analysis of ACADM can be used to confirm the diagnosis. […] In cases of sudden death where the preceding illness would not usually have been fatal, MCADD is often suspected.

• #2 MCADZ – Overview: Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency Full Gene Analysis, Varies

  https://www.mayocliniclabs.com/test-catalog/overview/35478

  Confirmation of diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (as a follow-up to biochemical analyses) […] Screening of at-risk carriers of MCAD deficiency when an affected relative has not had molecular testing […] Diagnosis of MCAD deficiency in autopsy specimens […] Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive inherited defect in the mitochondrial oxidation of fatty acids. […] Review of clinical features and biochemical analysis via plasma acylcarnitines (ACRN / Acylcarnitines, Quantitative, Plasma), fatty acid profile (FAO / Fatty Acid Oxidation Probe Assay, Fibroblast Culture), urine organic acids (OAU / Organic Acids Screen, Random, Urine), and urine acylglycines (ACYLG / Acylglycines, Quantitative, Urine) are always recommended as the initial evaluation for MCAD.

• #2 Medium chain acyl-CoA dehydrogenase deficiency (MCADD)

  https://www.medicalnewstoday.com/articles/medium-chain-acyl-coa-dehydrogenase-deficiency

  Newborn screenings help diagnose MCADD early. Early diagnosis and proper management can lead to a very good outlook for someone with the condition. […] Newborn screenings help healthcare professionals confirm many MCADD diagnoses and have improve health outcomes. They help parents and caregivers better understand the condition and learn how to prevent hypoglycemia early on. […] If an adult develops MCADD symptoms, doctors can order the same tests used during newborn screenings to make a diagnosis.

• #2 Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-102

  Our study points to that the ACADM genotype most commonly seen in MCADD might be of particular relevance in refining a follow-up protocol, since plasma carnitine levels in patients homozygous for c.985AG tend to be lower and supplementation is required to maintain carnitine within the normal range. […] By demonstrating an association between carnitine levels and homozygosity for the c.985AG mutation, the current study also contributes to our understanding of the relationship between genotype/biochemical markers and phenotype in MCADD.

• #2

  https://www.gov.uk/government/publications/mcadd-suspected-description-in-brief/mcadd-detailed-information

  With prompt use of the emergency regimen and avoidance of prolonged fasting, the outcome is usually very good and most children will avoid any long-term health problems. […] Children from the same parents have a 1 in 4 chance of having MCADD. Your other children might be at risk of MCADD even if they have never shown any symptoms. It is therefore very important to get them tested if they have not been previously screened for MCADD. Your metabolic team will be able to arrange this testing. […] A new baby from the same parents will also have a 1 in 4 chance of having MCADD. When you find out that you are pregnant, you should tell your midwife and GP that there is a family history of MCADD. You should also inform your metabolic team early in the pregnancy.

• #2 SciELO Brazil – The value of fasting in the diagnosis of medium-chain acyl-CoA dehydrogenase deficiency The value of fasting in the diagnosis of medium-chain acyl-CoA dehydrogenase deficiency

  https://www.scielo.br/j/jbpml/a/5XncHP8LCqMFg3v94csrgQC/

  From the laboratory point of view, this case shows the importance of fasting prior to sample collection (if possible) when a mitochondrial fatty acid beta-oxidation disorder is suspected. […] Considering the possibility that MCADD is underdiagnosed in Brazil and is known to be a cause of sudden death in children, it is important to emphasize that the timing/momentum of biological sample collection may be crucial for proper diagnosis and management.

• #2 Untargeted Metabolomics Identifies Biomarkers for MCADD Neonates in Dried Blood Spots

  https://www.mdpi.com/1422-0067/24/11/9657

  Our findings suggest that MCADD newborns may have oxidative stress events as signs of the disease. […] However, further validations of these biomarkers are needed in future studies to ensure their accuracy and reliability as complementary markers with established MCADD markers for clinical diagnosis. […] Our study has fully exploited the benefits and capabilities of untargeted metabolomics to identify metabolic biomarkers/pathways for MCADD. […] These findings may be used as potential biomarkers for MCADD as a complementary diagnostic approach in addition to the most currently known acylcarnitine biomarkers. […] Thus, after further validation studies, glutathione could also be used as a potential metabolic biomarker for MCADD.

• #2 MCAD Deficiency: Symptoms, Treatment, Life Expectancy

  https://www.verywellhealth.com/mcad-overview-4175022

  If MCAD deficiency is properly managed, a person can live a long and healthy life. However, if left undiagnosed and untreated, the risk of death is estimated to be around 20%. Most deaths occur during early childhood. […] MCAD deficiency is a rare genetic condition that affects the body’s ability to convert certain fats into energy. The deficiency occurs when two parents with a specific gene mutation pass it to their child. If the condition goes undiagnosed and untreated, it can be fatal. […] People with MCAD deficiency usually need to adhere to a diet that is high in carbohydrates and low in fat. They also need to avoid long periods of fasting. If properly managed, most people with MCAD deficiency can lead normal, healthy lives.

• #2 Newborn screening information for medium-chain acyl-CoA dehydrogenase deficiency | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency

  Children who receive early treatment for medium-chain acyl-CoA dehydrogenase deficiency (MCAD) have healthy growth and development. […] If MCAD is not treated, children may experience breathing problems, seizures, liver troubles, brain damage, coma, and possibly death. Early screening and treatment can avoid these effects. […] Because MCAD is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for MCAD, and understand what this diagnosis means for other family members and future pregnancies.

• #2 MCADD (medium chain acyl-CoA dehydrogenase deficiency) – newbornscreening.info

  https://www.newbornscreening.info/mcadd-medium-chain-acyl-coa-dehydrogenase-deficiency/

  MCADD occurs when an enzyme called medium chain acyl-CoA dehydrogenase (MCAD), is either missing or not working properly. This enzymes job is to break down certain fats in the food we eat into energy. It also breaks down fat already stored in the body. […] MCADD can cause bouts of illness called metabolic crises. Children with MCADD often show effects for the first time between three months and three years of age. […] Your babys primary doctor will work with a metabolic doctor to care for your child. […] With prompt and careful treatment, children with MCADD usually live healthy lives with typical growth and development. The goal of treatment is to prevent long-term problems. […] Genetic testing for MCADD can be done on a blood sample. […] MCADD can also be confirmed either by a blood test called an acylcarnitine profile or an enzyme test on a skin sample.

• #2 MCAD Deficiency: Symptoms, Treatment, Life Expectancy

  https://www.verywellhealth.com/mcad-overview-4175022

  Medium chain acyl-coenzyme A dehydrogenase deficiency (MCAD deficiency) is a rare and potentially serious inherited condition that affects the body’s ability to convert a certain fat into energy. […] Today, testing for MCAD deficiency is part of standard newborn screenings in the United States. […] The U.S. Department of Health and Human Services recommends MCAD deficiency testing as part of routine newborn screening. The primary benefit of screening is that an infant can be diagnosed before symptoms develop. […] If the screening indicates MCAD deficiency, additional testing can provide more information. […] Other tests used to confirm a diagnosis of MCAD deficiency include: Genetic testing to look for specific ACADM gene mutations, Blood tests to measure glucose, ammonia, liver enzymes, and other levels, Urine tests to rule out other conditions that cause low blood sugar.

• #3 Diagnosis and Discussion – Case 1076 | Department of Pathology

  https://www.path.pitt.edu/diagnosis-and-discussion-case-1076

  Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD). […] Based on clinical and laboratory presentation along with confirmatory biochemical genetic results, the diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) was made. […] MCAD should be suspected in an infant with positive newborn screening result, previously healthy individuals who become symptomatic, or in sudden unexpected death. Our patient was previously healthy and presented with lethargy and hypoketotic hypoglycemia on day 3. […] The diagnosis is established by confirmatory biochemical testing (plasma acylcarnitine) and pathogenic variants in the ACADM gene. […] Acylcarnitine analysis show increased concentrations of octanoylcarnitine (C8) along with lesser elevated concentrations of C6-, C10-, and C10:1-acylcarnitines.

• #3 Diagnosis and Discussion – Case 1076 | Department of Pathology

  https://www.path.pitt.edu/diagnosis-and-discussion-case-1076

  Urine organic acid and urine acyl glycine analysis can also provide supportive evidence of MCADD deficiency. […] Increased levels of hexanoylglycine (C6), octanoylglycine (C8), decanoylglycine (C10) along with low ketone are usual pattern on urine organic acid analysis. […] The parents of an affected child are carriers of at least one ACADM pathogenic variant. […] However, with the broad application of newborn screening, this is no longer necessary.

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