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PubMed This is a summary of 67 peer-reviewed journal articles Updated
Metabolic medicine

Multiple acyl-CoA dehydrogenase deficiency: A Patient Guide

At a Glance

MADD limits the body's ability to use fats and some protein components for energy. Crisis risk is reduced by an individualized diet, avoiding prolonged fasting, supervised riboflavin when recommended, and a written emergency plan for illness.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare genetic disorder that fundamentally changes how your body converts food into energy. In most people, the body can switch between burning sugars, fats, and proteins depending on what is available. In MADD, the “electrical wiring” inside your cells’ power plants (the mitochondria) is impaired. Because of pathogenic variants in the ETFA, ETFB, or ETFDH genes, your body cannot efficiently harvest energy from fats and certain protein components [1][2]. This creates a metabolic bottleneck where the body struggles to find fuel, especially when it is under physical stress [3].

You may also hear this condition called Glutaric acidemia type II (GA2). While the names are interchangeable, it is vital to know that this is entirely different from Glutaric acidemia type I (GA1) [4]. While GA1 affects only a few specific protein components, MADD is a “multiple” deficiency that impacts many pathways at once, including the body’s primary way of burning fat [2][5]. This broad impact is why MADD can affect many different organ systems, from the muscles and heart to the liver and brain [6][7].

The experience of living with MADD is highly variable. Historically, doctors grouped cases into three types: some individuals are diagnosed as newborns with severe symptoms (Types I and II), while others may not show signs until childhood or even adulthood (Type III) [8]. For those with later-onset forms, the condition often appears as muscle weakness, pain, or exercise intolerance [9]. Regardless of the type, the primary goal of management is the same: keeping the body’s energy levels stable so it never has to rely on its impaired fat-burning system [10][11].

Managing MADD requires a proactive approach centered on three pillars: individualized nutrition, supplements, and emergency preparedness. This usually involves customized targets for dietary fat and protein, a reliance on carbohydrates for energy, and the strict avoidance of prolonged fasting [10]. Many people also benefit from a supervised trial of high-dose riboflavin (Vitamin B2), which can help the faulty energy-transfer system work more effectively [12][13].

Because illness or fasting can trigger a sudden and dangerous metabolic crisis, every patient must have a specialist-written emergency protocol. This ensures they receive immediate, life-saving treatment—like IV glucose—if they become sick [14][15]. While MADD is a complex condition, a dedicated metabolic team and a well-followed management plan allow many patients to lead stable, active lives [10].

Key Actions for Today:

  • Never fast for longer than the specific interval set by your metabolic team.
  • Follow your individualized dietary plan; do not self-restrict fats or proteins without guidance.
  • Ensure you have a physical copy of your emergency sick-day protocol easily accessible at all times.

In this guide

6 chapters

01

Understanding Your MADD/GA2 Diagnosis

Learn what a MADD/GA2 diagnosis means, how it differs from GA1, how neonatal and late-onset types vary, and what genetic testing and treatment may involve.

02

The Biology of Energy: Understanding MADD and Your Labs

Learn how to interpret Multiple acyl-CoA dehydrogenase deficiency (MADD) lab results, including acylcarnitines, urine organic acids, normal tests, and mimics.

03

Emergency Management: Navigating a Metabolic Crisis

Learn emergency management for multiple acyl-CoA dehydrogenase deficiency (MADD), including crisis red flags, IV glucose, and a sick-day protocol letter.

04

Treating MADD: Nutrition, Supplements, and Daily Life

Learn how to manage multiple acyl-CoA dehydrogenase deficiency (MADD) with personalized nutrition, riboflavin, frequent meals, and safe daily routines.

05

Daily Life and Long-Term Health with MADD

Learn how multiple acyl-CoA dehydrogenase deficiency affects daily life, including sick-day care, organ monitoring, diet risks, and emotional and social support.

06

Building Your Care Team and Understanding Genetics

Learn how specialized care teams, genetic testing, carrier risk, and family planning guide multiple acyl-CoA dehydrogenase deficiency (MADD) care options.

Common questions in this guide

What is multiple acyl-CoA dehydrogenase deficiency, and is it the same as GA2?
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inherited disorder that makes it difficult for the body to use fats and some protein components for energy. It is also called glutaric acidemia type II (GA2), but it is different from glutaric acidemia type I (GA1).
What causes MADD?
MADD is caused by disease-related changes in the ETFA, ETFB, or ETFDH genes. These genes are involved in transferring energy inside mitochondria, and the effects can vary widely between people.
Why can fasting be dangerous for someone with MADD?
During fasting, illness, or physical stress, the body needs to switch to stored fat and other fuels, but MADD limits that process. Follow the fasting interval set by your metabolic team and use the individualized meal plan rather than changing fat, protein, or carbohydrate intake on your own.
Can riboflavin help treat MADD?
Many people with MADD are offered a supervised trial of high-dose riboflavin, also called vitamin B2. It can help the impaired energy-transfer system work more effectively in some cases, but the dose and plan should come from the metabolic team.
What should I do if someone with MADD becomes sick?
Use the written emergency sick-day protocol and contact the metabolic team or emergency services as instructed. Illness can trigger a metabolic crisis, and urgent treatment may include intravenous glucose to provide energy while the body is under stress.
What symptoms can later-onset MADD cause?
Later-onset MADD may cause muscle weakness, muscle pain, and reduced ability to exercise. Fatigue or mood changes can be early signs that illness is starting, so follow the action plan from your clinical team.

Questions For You

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is the specific genetic cause of this diagnosis (ETFA, ETFB, or ETFDH), and what does it tell us about the expected course of the condition?
  2. 2.How long can I (or my child) safely go without eating during the day and overnight?
  3. 3.Is this case likely to be riboflavin-responsive, and what is our plan for testing that response?
  4. 4.Do we have a finalized, written emergency sick-day protocol and an emergency room letter?
  5. 5.Who is our primary point of contact for metabolic emergencies after hours or on weekends?

References

References (15)
  1. 1

    Electron transfer flavoprotein and its role in mitochondrial energy metabolism in health and disease.

    Henriques BJ, Katrine Jentoft Olsen R, Gomes CM, Bross P

    Gene 2021; (776()):145407 doi:10.1016/j.gene.2021.145407.

    PMID: 33450351
  2. 2

    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
  3. 3

    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
  4. 4

    A novel electron transfer flavoprotein dehydrogenase (ETFDH) gene mutation identified in a newborn with glutaric acidemia type II: a case report of a Chinese family.

    Ou M, Zhu L, Zhang Y, et al.

    BMC medical genetics 2020; (21(1)):98 doi:10.1186/s12881-020-00995-2.

    PMID: 32393189
  5. 5

    Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision.

    Boy N, Mühlhausen C, Maier EM, et al.

    Journal of inherited metabolic disease 2017; (40(1)):75-101 doi:10.1007/s10545-016-9999-9.

    PMID: 27853989
  6. 6

    "Liver Failure in an Infant of Late-Onset Glutaric Aciduria Type II": Case Report.

    Keshri S, Goel AK, Johns J, Shah S

    Indian journal of clinical biochemistry : IJCB 2023; (38(4)):545-549 doi:10.1007/s12291-021-01007-7.

    PMID: 37746538
  7. 7

    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
  8. 8

    MADD-like pattern of acylcarnitines associated with sertraline use.

    Ingoglia F, Tanfous M, Ellezam B, et al.

    Molecular genetics and metabolism reports 2024; (41()):101142 doi:10.1016/j.ymgmr.2024.101142.

    PMID: 39318848
  9. 9

    Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease.

    Béhin A, Acquaviva-Bourdain C, Souvannanorath S, et al.

    Revue neurologique 2016; (172(3)):231-41.

    PMID: 27038534
  10. 10

    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
  11. 11

    Stealthy progression of type 2 diabetes mellitus due to impaired ketone production in an adult patient with multiple acyl-CoA dehydrogenase deficiency.

    Ikeda N, Wada Y, Izumi T, et al.

    Molecular genetics and metabolism reports 2024; (38()):101061 doi:10.1016/j.ymgmr.2024.101061.

    PMID: 38469101
  12. 12

    ETF dehydrogenase advances in molecular genetics and impact on treatment.

    Missaglia S, Tavian D, Angelini C

    Critical reviews in biochemistry and molecular biology 2021; (56(4)):360-372 doi:10.1080/10409238.2021.1908952.

    PMID: 33823724
  13. 13

    Clinical, pathological and genetic features and follow-up of 110 patients with late-onset MADD: a single-center retrospective study.

    Wen B, Tang S, Lv X, et al.

    Human molecular genetics 2022; (31(7)):1115-1129 doi:10.1093/hmg/ddab308.

    PMID: 34718578
  14. 14

    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
  15. 15

    Myogenic Disease and Metabolic Acidosis: Consider Multiple Acyl-Coenzyme A Dehydrogenase Deficiency.

    Dernoncourt A, Bouchereau J, Acquaviva-Bourdain C, et al.

    Case reports in critical care 2019; (2019()):1598213 doi:10.1155/2019/1598213.

    PMID: 31934457

This page about MADD is for informational purposes only and does not constitute medical advice. Your metabolic team should set your individualized diet, riboflavin plan, safe fasting limits, and emergency protocol; seek urgent care for possible metabolic crisis.