Skip to content
How It Works
Explore
Ask a Question Resources Pricing
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Sign Up
PubMed This is a summary of 15 peer-reviewed journal articles Updated
Pediatric Endocrinology · Corticosterone Methyloxidase Type II Deficiency

The Biology of CMO II Deficiency: How Salt Balance Works

At a Glance

CMO II deficiency is a rare disorder in which the adrenal glands make too little aldosterone, the hormone that helps the kidneys retain salt and water. Cortisol is usually normal, so confirmed cases often need fludrocortisone and prescribed salt rather than routine hydrocortisone.

Understanding why your child’s body is losing salt requires looking at a specific “instruction manual” in the body: the CYP11B2 gene [1]. This gene provides the instructions for making an enzyme called aldosterone synthase [2]. When this enzyme doesn’t work correctly, the result is a salt-wasting condition known as Corticosterone Methyloxidase (CMO) deficiency [3].

The Role of Aldosterone

Aldosterone is often called the “salt-retaining hormone” [4]. It is produced in the outer layer of the adrenal glands and travels to the kidneys, where it acts as a signal to:

  • Keep Sodium: It tells the kidneys to pull salt back into the bloodstream rather than letting it leave through urine [4][5].
  • Release Potassium: It helps the body get rid of extra potassium [4].
  • Maintain Blood Volume: By keeping salt, the body also keeps water, which maintains healthy blood volume and pressure [4][6].

In children with CMO II deficiency, the lack of aldosterone means salt and water are “wasted” in the urine, leading to dehydration and dangerous electrolyte imbalances [3][7].

CMO I vs. CMO II: What’s the Difference?

The aldosterone synthase enzyme performs three separate chemical “jobs” to turn a precursor molecule into aldosterone [2]. Doctors distinguish between Type I and Type II based on which step is blocked:

  • CMO I (18-hydroxylase deficiency): The enzyme fails at an earlier step. These children have very low levels of both aldosterone and its intermediate building blocks [7][6].
  • CMO II (18-oxidase deficiency): The enzyme fails at the very last step. Interestingly, these children often have very high levels of the building block 18-hydroxycorticosterone because the body can make it but can’t finish the job of turning it into aldosterone [6][8].

Distinguishing CMO II from “Look-Alike” Conditions

Because CMO II is rare, it can initially be confused with other conditions that cause salt-wasting in infants [1][3]. Accurate diagnosis by a specialist is vital because the treatments are very different.

Condition Primary Issue Key Difference from CMO II
Classic Salt-Wasting 21-Hydroxylase Deficiency (CAH) A block in both cortisol and aldosterone production [9]. Also involves high androgens (male hormones) and low cortisol. Requires routine steroid replacement (hydrocortisone) [3][9].
Pseudohypoaldosteronism (PHA1) The body makes aldosterone, but the kidneys are “deaf” to its signal [10]. Aldosterone levels are typically very high, not low. It does not respond to aldosterone-replacement medication [3][11].
Secondary Pseudohypoaldosteronism Temporary salt-wasting caused by a urinary tract infection (UTI) or kidney malformation. Resolves once the underlying infection or kidney issue is treated.
Adrenal Hypoplasia Congenita The adrenal glands are underdeveloped from birth [12]. Affects all adrenal hormones, including cortisol. Often associated with other issues like delayed puberty [12][13].

Why an Accurate Diagnosis Matters

In isolated CMO II deficiency, the “stress hormone” cortisol is usually produced normally [1][3]. This is a critical distinction. In conditions like classic CAH or Adrenal Hypoplasia, children must take glucocorticoids (like hydrocortisone) daily or during illness to replace missing cortisol [9].

When isolated CMO II is confirmed, children usually only need mineralocorticoids (like fludrocortisone) and prescribed salt [14][15]. Over-treating a child with CMO II by giving them unnecessary daily glucocorticoids can lead to unwanted side effects, such as slowed growth [15]. Conversely, if doctors suspect an adrenal crisis or are unsure of the exact diagnosis in an emergency, they may still administer empiric hydrocortisone. Never refuse emergency steroids if a clinician believes your child is in crisis, and never start or stop glucocorticoids without your endocrinologist’s strict direction.

Common questions in this guide

What causes CMO II deficiency?
CMO II deficiency results from reduced activity of the CYP11B2 gene product, aldosterone synthase. The enzyme cannot complete the final step needed to make aldosterone, so the kidneys lose too much salt and water; cortisol production is usually preserved in isolated CMO II deficiency.
How is CMO II different from CMO I?
CMO I involves an earlier step in aldosterone production and usually causes low levels of aldosterone and its intermediate building blocks. CMO II affects the final step, so 18-hydroxycorticosterone often builds up while aldosterone remains low.
How do doctors tell CMO II deficiency apart from CAH or pseudohypoaldosteronism?
Doctors compare hormone patterns, medical history, and test results. Classic salt-wasting CAH also causes low cortisol and high androgen levels, while pseudohypoaldosteronism usually has very high aldosterone because the kidneys do not respond to it. A temporary form of pseudohypoaldosteronism can occur with a urinary infection or kidney problem and may improve when that issue is treated.
Does a child with CMO II deficiency need hydrocortisone?
In isolated CMO II deficiency, cortisol production is usually normal, so routine daily hydrocortisone may not be needed. Treatment often focuses on fludrocortisone and prescribed salt, but clinicians may give hydrocortisone during a suspected adrenal crisis or when the diagnosis is uncertain. Medication decisions should always come from the child’s endocrinologist.
What tests can help confirm CMO II deficiency?
A urinary steroid profile using gas chromatography-mass spectrometry can help distinguish CMO I from CMO II by showing which hormone building blocks are present. Genetic testing of CYP11B2 can provide additional support for the diagnosis, alongside the child’s hormone results and clinical findings.
What should I do if my child cannot keep down salt or medicine during a stomach bug?
Contact the child’s pediatric endocrinology team or on-call service promptly if vomiting prevents the child from taking prescribed salt or medicine. Worsening dehydration, inability to keep fluids down, or concern for an adrenal crisis requires urgent medical evaluation, where intravenous fluids and emergency treatment may be needed.

Get notified when new evidence is published on corticosterone methyloxidase type 2 deficiency.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References

References (15)
  1. 1

    Congenital aldosterone deficiency and its resistance.

    Tajima T, Amano N, Ishii T, et al.

    Endocrine journal 2026; (73(6)):751-763 doi:10.1507/endocrj.EJ25-0630.

    PMID: 41905953
  2. 2

    Human cytochrome P450 11B2 produces aldosterone by a processive mechanism due to the lactol form of the intermediate 18-hydroxycorticosterone.

    Reddish MJ, Guengerich FP

    The Journal of biological chemistry 2019; (294(35)):12975-12991 doi:10.1074/jbc.RA119.009830.

    PMID: 31296661
  3. 3

    Clinical and Genetic Characteristics of Patients with Corticosterone Methyloxidase Deficiency Type 2: Novel Mutations in CYP11B2

    Turan H, Dağdeviren Çakır A, Özer Y, et al.

    Journal of clinical research in pediatric endocrinology 2021; (13(2)):232-238 doi:10.4274/jcrpe.galenos.2020.2019.0216.

    PMID: 32539318
  4. 4

    Aldosterone synthase inhibition: a novel bullet to fight cardiovascular-kidney-metabolic syndrome.

    Barrera-Chimal J, Vaidya A, Jaisser F

    Journal of molecular endocrinology 2025; (75(3)).

    PMID: 40911485
  5. 5

    Aldosterone-dependent and -independent regulation of Na+ and K+ excretion and ENaC in mouse kidneys.

    Yang L, Frindt G, Xu Y, et al.

    American journal of physiology. Renal physiology 2020; (319(2)):F323-F334 doi:10.1152/ajprenal.00204.2020.

    PMID: 32628540
  6. 6

    Deciphering aldosterone deficiency and pseudodeficiency in infancy by targeted GC-MS urinary steroid metabotyping.

    Li H, Pons-Kühnemann J, Hartmann MF, Wudy SA

    The Journal of steroid biochemistry and molecular biology 2027; (265()):107103 doi:10.1016/j.jsbmb.2026.107103.

    PMID: 42603653
  7. 7

    A novel compound heterozygous mutation in CYP11B2 (p.A153P and p.Q337*) associated with primary hypoaldosteronism.

    Yang J, Li L, Sun Y, et al.

    Frontiers in medicine 2026; (13()):1740124 doi:10.3389/fmed.2026.1740124.

    PMID: 41889508
  8. 8

    Structural and clinical characterization of CYP11B2 inhibition by dexfadrostat phosphate.

    Pignatti E, Kollar J, Hafele E, et al.

    The Journal of steroid biochemistry and molecular biology 2023; (235()):106409 doi:10.1016/j.jsbmb.2023.106409.

    PMID: 37827219
  9. 9

    Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected.

    Gao J, Chen L

    Frontiers in pediatrics 2020; (8()):464 doi:10.3389/fped.2020.00464.

    PMID: 32903448
  10. 10

    Pseudohypoaldosteronism types I and II: little more than a name in common.

    Casas-Alba D, Vila Cots J, Monfort Carretero L, et al.

    Journal of pediatric endocrinology & metabolism : JPEM 2017; (30(5)):597-601.

    PMID: 28593901
  11. 11

    Clinical and molecular characteristics of a series of Chinese children with pseudohypoaldosteronism: a case series.

    Wu Z, Li J, Sheng H, et al.

    Translational pediatrics 2026; (15(3)):82 doi:10.21037/tp-2025-1-844.

    PMID: 41982973
  12. 12

    Patient with adrenal insufficiency due to a de novo mutation in the NR0B1 gene.

    Bravo Nieto D, García Fernández AS, Díaz Troyano N, et al.

    Advances in laboratory medicine 2023; (4(2)):195-202 doi:10.1515/almed-2023-0018.

    PMID: 38075942
  13. 13

    Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience.

    Bizzarri C, Olivini N, Pedicelli S, et al.

    Italian journal of pediatrics 2016; (42(1)):73 doi:10.1186/s13052-016-0282-3.

    PMID: 27485500
  14. 14

    Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency.

    Gurpinar Tosun B, Kendir Demirkol Y, Seven Menevse T, et al.

    The Journal of clinical endocrinology and metabolism 2022; (107(1)):e106-e117 doi:10.1210/clinem/dgab619.

    PMID: 34415991
  15. 15

    Severe Aldosterone Synthase Deficiency in a 9-Day-Old Lebanese Boy: The Importance of Functional Studies to Establish Pathogenicity of Seemingly Benign Variants in CYP11B2.

    Ghaddhab C, Capper CP, Larrivée-Vanier S, et al.

    Hormone research in paediatrics 2025; (98(1)):96-102 doi:10.1159/000536437.

    PMID: 38316111

This page explains CMO II deficiency and salt balance for informational purposes only and does not constitute medical advice. Your child’s pediatric endocrinologist should interpret test results and direct medication, salt, and emergency care decisions.

Guide contents corticosterone methyloxidase type 2 deficiency
Research & Literature
01 Understanding Your Child's Diagnosis of CMO II Deficiency 03 Recognizing Symptoms and Emergency Red Flags