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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Biochemical genetics

Building Your Care Team and Understanding Genetics

At a Glance

People with MADD benefit from a specialized metabolic team, a dietitian, and a written emergency plan. Genetic counseling can explain advanced testing, carrier results, and the 25% chance of MADD in each pregnancy when both parents carry a change in the same gene.

Because Multiple acyl-CoA dehydrogenase deficiency (MADD) is an ultra-rare condition, your care requires a specialized team that looks beyond standard medicine [1]. You are not just looking for a doctor; you are building a “medical home” where experts coordinate to protect your energy levels and organ health [2][3].

Your Core Medical Team

Your care should be anchored by a metabolic center, typically located at a major university or children’s hospital. Your core team usually includes:

  • Biochemical Geneticist (Metabolic Specialist): The “quarterback” of your team who understands the complex chemistry of MADD and manages your treatment protocols [4][1].
  • Metabolic Dietitian: A specialist who calculates your specific nutritional needs, ensuring you get enough carbohydrates while setting individualized, safe targets for fat and protein [5][6].

Depending on your symptoms and specific phenotype, your specialist may refer you to:

  • Cardiologist: To monitor for cardiomyopathy (heart muscle issues), if clinically indicated by your baseline tests or onset type [2][7].
  • Neurologist: To monitor muscle strength, nerve health, and coordination issues [8][9].

Evaluating Your Team

When meeting a new specialist, it is okay to ask questions. A prepared team for MADD should be able to say “yes” to these three things:

  1. Direct Experience: “We have treated other patients with MADD or similar fatty acid oxidation disorders.”
  2. Emergency Access: “We provide a 24/7 emergency contact for you and for any ER doctor who might treat you.” [4]
  3. Written Protocols: “We will provide you with a written Sick Day Protocol and letters for school, travel, and surgery.” [4]

Advanced Genetic Testing

Most people with MADD have mutations in the ETFA, ETFB, or ETFDH genes [10]. However, standard genetic panel testing does not always uncover the complete picture.

If your biochemical tests (like your acylcarnitine profile) strongly point to MADD but standard genetic sequencing is “negative” or only finds one mutation, a genetics professional will decide if advanced testing is appropriate [11][12]. These tests are not automatically needed and can be expensive or yield uncertain results, but options include:

  • Deletion/Duplication Analysis (MLPA): Checks for large missing or extra chunks of DNA [13].
  • RNA Sequencing: Looks at how your cells “read” instructions, which can find mutations hidden deep inside the gene (deep intronic variants) [14][15].
  • Whole Genome Sequencing (WGS): A comprehensive scan of your entire genetic code [15].

Family Planning and Recurrence

MADD is an autosomal recessive condition [16]. This means that for a person to have MADD, they usually must inherit one mutated gene from each parent [12].

  • The 25% Rule: If both parents are “carriers” of a pathogenic variant in the exact same gene (e.g., both carry an ETFDH mutation), each of their children has a 25% (1 in 4) chance of having MADD [12][17]. There is a 50% chance the child will be a carrier like the parents, and a 25% chance they will not have the condition or carry the gene.
  • Genetic Counseling: It is highly recommended that families meet with a genetic counselor [18]. They can help interpret confusing test results, coordinate carrier testing for relatives, and discuss family planning options [14][18].
  • Predicting Severity: It is important to know that even within the same family, MADD can look very different [19]. One sibling might have a more severe form while another has a much milder form, even with the exact same genetic mutations [20][21]. Your care must be based on your specific symptoms, not just your genetic code.

Common questions in this guide

Which doctors are usually involved in MADD care?
Care is usually anchored by a specialized metabolic center with a biochemical geneticist or metabolic specialist and a metabolic dietitian. A cardiologist or neurologist may join the team when baseline tests, symptoms, or the specific form of MADD indicate a need.
What can happen if standard genetic testing does not find all the MADD mutations?
If biochemical testing, such as an acylcarnitine profile, strongly suggests MADD, a genetics professional may consider deletion and duplication analysis, RNA sequencing, or whole-genome sequencing. These tests are not automatically needed and may be expensive or produce results that are difficult to interpret.
What is the chance that two MADD carriers will have an affected child?
When both parents carry a disease-causing variant in the same gene, each pregnancy has a 25% chance of resulting in a child with MADD. There is also a 50% chance the child will be a carrier and a 25% chance the child will have neither the condition nor a carrier variant.
How can genetic counseling help a family affected by MADD?
A genetic counselor can explain genetic test results, arrange carrier testing for relatives, and discuss family-planning options. Counseling can also help families understand recurrence risk without assuming that every family member will have the same symptoms.
Can siblings with MADD have different symptoms or severity?
Yes. MADD can look different even among siblings who have the same genetic changes, with one person having a more severe form and another having milder symptoms. Care and monitoring should be based on each person's symptoms and medical findings, not on genetic results alone.
What should be included in an emergency plan for MADD?
A useful plan includes a written sick-day protocol, letters explaining the condition for emergency clinicians, and a 24/7 contact for the metabolic team. Copies may also be needed for school, travel, surgery, and other healthcare settings.

Questions For You

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How many other MADD or Glutaric Acidemia Type II patients are currently followed by this clinic?
  2. 2.Does the clinic have a metabolic dietitian on staff who can help me calculate exact protein and fat targets?
  3. 3.If my initial genetic testing only found one mutation (or none), do you recommend consulting a geneticist about advanced sequencing?
  4. 4.Is there a 24/7 on-call metabolic specialist I can reach if I need to go to a local emergency room?
  5. 5.What is your process for coordinating care with my other doctors, if referrals to cardiology or neurology become necessary?

References

References (21)
  1. 1

    [Consensus on screening, diagnosis and treatment of multiple acyl-CoA dehydrogenase deficiency].

    Division Of Genetics And Metabolomics Child Diseases And Health Care Branch Chinese Association For Maternal And Child Health , Chen X, Sun Y, et al.

    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2021; (38(5)):414-418 doi:10.3760/cma.j.cn511374-20200829-00630.

    PMID: 33974246
  2. 2

    Late-onset multiple acyl-CoA dehydrogenase deficiency: an insidious presentation.

    Rao NN, Burns K, Manolikos C, Hodge S

    BMJ case reports 2023; (16(5)) doi:10.1136/bcr-2022-252668.

    PMID: 37217231
  3. 3

    Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency.

    Henriques BJ, Lucas TG, Martins E, et al.

    Current molecular medicine 2019; (19(7)):487-493 doi:10.2174/1566524019666190507114748.

    PMID: 31418342
  4. 4

    Glutaric acidemia type 2 presenting as a surgical acute abdomen: a case of unnecessary exploratory laparotomy in an adult.

    Bilal PK, Erkoç SK, Polat B, et al.

    Archive of clinical cases 2026; (13(3)):108-111 doi:10.22551/2026.52.1303.10350.

    PMID: 42751163
  5. 5

    Management of Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) in Pregnancy.

    Shear MA, LaTray A, Chang IJ, et al.

    Metabolites 2025; (15(7)) doi:10.3390/metabo15070432.

    PMID: 40710532
  6. 6

    Successful Pregnancy in a Young Woman with Multiple Acyl-CoA Dehydrogenase Deficiency.

    Creanza A, Cotugno M, Mazzaccara C, et al.

    JIMD reports 2018; (39()):1-6 doi:10.1007/8904_2017_38.

    PMID: 28685490
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    Cardiologic evaluation of Turkish mitochondrial fatty acid oxidation disorders.

    Balci MC, Karaca M, Ergul Y, et al.

    Pediatrics international : official journal of the Japan Pediatric Society 2022; (64(1)):e15317 doi:10.1111/ped.15317.

    PMID: 36331231
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    Diagnostic Challenges in Late Onset Multiple Acyl-CoA Dehydrogenase Deficiency: Clinical, Morphological, and Genetic Aspects.

    Lupica A, Oteri R, Volta S, et al.

    Frontiers in neurology 2022; (13()):815523 doi:10.3389/fneur.2022.815523.

    PMID: 35309592
  9. 9

    Severe sensory neuropathy in patients with adult-onset multiple acyl-CoA dehydrogenase deficiency.

    Wang Z, Hong D, Zhang W, et al.

    Neuromuscular disorders : NMD 2016; (26(2)):170-5.

    PMID: 26821934
  10. 10

    Disorders of flavin adenine dinucleotide metabolism: MADD and related deficiencies.

    Mereis M, Wanders RJA, Schoonen M, et al.

    The international journal of biochemistry & cell biology 2021; (132()):105899 doi:10.1016/j.biocel.2020.105899.

    PMID: 33279678
  11. 11

    Newborn screening and molecular features of patients with multiple acyl-CoA dehydrogenase deficiency in Quanzhou, China.

    Lin Y, Zhang W, Chen Z, et al.

    Journal of pediatric endocrinology & metabolism : JPEM 2021; (34(5)):649-652 doi:10.1515/jpem-2020-0694.

    PMID: 33823107
  12. 12

    Deep Intronic ETFDH Variants Represent a Recurrent Pathogenic Event in Multiple Acyl-CoA Dehydrogenase Deficiency.

    Martino S, D'Addabbo P, Turchiano A, et al.

    International journal of molecular sciences 2024; (25(17)) doi:10.3390/ijms25179637.

    PMID: 39273584
  13. 13

    Expanded newborn screening for inherited metabolic disorders and genetic characteristics in a southern Chinese population.

    Lin Y, Zheng Q, Zheng T, et al.

    Clinica chimica acta; international journal of clinical chemistry 2019; (494()):106-111 doi:10.1016/j.cca.2019.03.1622.

    PMID: 30904546
  14. 14

    Role of RNA in Molecular Diagnosis of MADD Patients.

    Nogueira C, Silva L, Marcão A, et al.

    Biomedicines 2021; (9(5)) doi:10.3390/biomedicines9050507.

    PMID: 34064479
  15. 15

    A novel deleterious ETFA promoter variant causative of multiple acyl-CoA dehydrogenase deficiency.

    Prasun P, Evans A, Cork E, et al.

    American journal of medical genetics. Part A 2023; (191(4)):1089-1093 doi:10.1002/ajmg.a.63104.

    PMID: 36579410
  16. 16

    Mitochondrial energetic impairment in a patient with late-onset glutaric acidemia Type 2.

    Xiao C, Astiazaran-Symonds E, Basu S, et al.

    American journal of medical genetics. Part A 2020; (182(10)):2426-2431 doi:10.1002/ajmg.a.61786.

    PMID: 32804429
  17. 17

    A fatal case of neonatal onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutation of ETFDH gene: case report.

    De Pasquale L, Meo P, Fulia F, et al.

    Italian journal of pediatrics 2022; (48(1)):164 doi:10.1186/s13052-022-01356-w.

    PMID: 36064718
  18. 18

    First report of neonatal-onset glutaric aciduria type II in the Iranian population caused by a novel deleterious ETFA variant.

    Parvini F, Ajam-Hosseini M, Shadpour M

    Orphanet journal of rare diseases 2025; (20(1)):590 doi:10.1186/s13023-025-04107-2.

    PMID: 41254678
  19. 19

    Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe.

    Staretz-Chacham O, Amar S, Almashanu S, et al.

    Genes 2021; (12(8)) doi:10.3390/genes12081140.

    PMID: 34440319
  20. 20

    Case report: A novel c.1842_1845dup mutation of ETFDH in two Chinese siblings with multiple acyl-CoA dehydrogenase deficiency.

    Yuan G, Zhang X, Chen T, Lin J

    Frontiers in pediatrics 2022; (10()):1038440 doi:10.3389/fped.2022.1038440.

    PMID: 36683804
  21. 21

    Exploring the contribution of mitochondrial dynamics to multiple acyl-CoA dehydrogenase deficiency-related phenotype.

    Brandão SR, Ferreira R, Rocha H

    Archives of physiology and biochemistry 2021; (127(3)):210-216 doi:10.1080/13813455.2019.1628065.

    PMID: 31215835

This page is for informational purposes only and does not constitute medical advice. Your metabolic specialist and genetic counselor should interpret test results and tailor care, nutrition, and family-planning guidance to your situation.