What Does ICD-10 Code E72.20 Mean?
ICD-10 code E72.20 — Disorder of urea cycle metabolism, unspecified — is a billable diagnosis code used when a patient has a confirmed urea cycle disorder (UCD) but the specific enzymatic defect cannot be identified from available documentation. It falls under category E72 (Other disorders of amino-acid metabolism) within the Endocrine, Nutritional and Metabolic Diseases chapter (E00–E89) of the ICD-10-CM Official Coding Guidelines.
Key attributes of this code at a glance:
- Valid and billable for FY 2026 (October 1, 2025 – September 30, 2026)
- Applicable settings: Inpatient and outpatient — both default to “Yes”
- Chronic condition code per CMS classification
- Complication/Comorbidity (CC) designation — impacts MS-DRG weight when used as a secondary diagnosis
- Introduced with the initial ICD-10-CM implementation in FY 2016; no description changes since
What Conditions and Diagnoses Does E72.20 Cover?
E72.20 is the appropriate code when a urea cycle disorder is documented and confirmed, but the specific enzyme deficiency has not been — or cannot be — identified. Urea cycle disorders are rare, inherited metabolic conditions caused by mutations affecting enzymes that convert ammonia into urea for excretion via the kidneys.
Clinical presentations appropriately reported with E72.20 include:
- Confirmed hyperammonemia attributed to an unspecified urea cycle enzyme defect
- Neonatal onset UCD with lethargy, vomiting, hypotonia, seizures, and respiratory alkalosis where the specific defect is pending genetic confirmation
- Childhood or adult onset metabolic encephalopathy linked to a known UCD diagnosis where enzyme specificity is not yet documented
- Recurrent hyperammonemic episodes in a patient with a prior UCD diagnosis where the specific subtype is not carried forward in the encounter documentation
What Does E72.20 Specifically Exclude?
The following codes carry a Type 1 Excludes note against E72.20 — meaning they must never be reported simultaneously with E72.20:
| Excluded Code | Condition | Reason |
|---|---|---|
| E72.4 | Hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome | Distinct, specifically defined disorder |
| P74.6 | Transient hyperammonemia of newborn | Acquired/transient — not a congenital enzymatic defect |
Additionally, the broader E72 category excludes disorders of aromatic amino-acid metabolism (E70.–), branched-chain amino-acid metabolism (E71.0–E71.2), fatty-acid metabolism (E71.3), and purine/pyrimidine metabolism (E79.–).
When Is E72.20 the Right Code to Use?
E72.20 is a valid code of last resort within the urea cycle subcategory — meaning it is appropriate only after the coder has verified that no more specific code applies. Use the following decision criteria:
- Confirm the provider has documented a urea cycle disorder or disorder of urea cycle metabolism as the diagnosis.
- Review the record for any enzyme-specific language (e.g., OTC deficiency, CPS1 deficiency, ASS1 deficiency, argininosuccinic aciduria, arginase deficiency). If present, a specific code from E72.21–E72.29 applies instead.
- Confirm that HHH syndrome (E72.4) and transient neonatal hyperammonemia (P74.6) have been ruled out.
- Verify that the unspecified designation reflects a true gap in clinical documentation — not a coder’s failure to query the provider.
- If the specific enzyme defect is pending (e.g., genetic testing ordered but results not yet returned), E72.20 is acceptable for the current encounter. Amend or update when results are available.
How Does E72.20 Differ From Codes in the E72.21–E72.29 Range?
In practice, coders frequently encounter situations where a specialist note references “urea cycle disorder” without naming the enzyme — this is the exact scenario E72.20 is designed for. The E72.2x subcategory breaks down as follows:
| Code | Condition | Distinguishing Feature |
|---|---|---|
| E72.20 | UCD, unspecified | No enzyme identified in documentation |
| E72.21 | Disorder of ornithine transcarbamylase (OTC) | Most common UCD; X-linked; OTC deficiency documented |
| E72.22 | Carbamylphosphate synthetase I (CPS1) deficiency | Rare; autosomal recessive; CPS1 deficiency documented |
| E72.23 | Argininosuccinic aciduria (ASA lyase deficiency) | Elevated argininosuccinic acid on amino acid panel |
| E72.29 | Other disorders of urea cycle metabolism | Specific enzyme named but not listed above (e.g., arginase deficiency, citrullinemia) |
Auditors commonly flag E72.20 on claims where the medical record actually contains enzyme-specific language — a specificity error that can trigger medical necessity denials or compliance concerns.
What Documentation Is Required to Support E72.20?
What Must the Provider Document in the Clinical Notes?
The clinical record must contain enough detail to justify the “unspecified” designation — not just a vague reference to metabolic disease. Required documentation elements:
- Explicit diagnosis statement — the provider must use language such as “urea cycle disorder,” “disorder of urea cycle metabolism,” or a recognized clinical synonym (e.g., “inborn error of urea cycle metabolism”)
- Reason specificity is unavailable — e.g., “enzyme defect pending genetic workup,” “family history of UCD without confirmed subtype,” or “diagnosis established at outside facility without records”
- Clinical presentation consistent with UCD — hyperammonemia, encephalopathy, metabolic alkalosis, dietary protein intolerance documented
- Treatment or management plan referencing the UCD diagnosis (e.g., nitrogen scavenger therapy, dietary protein restriction, ammonia monitoring)
- Provider attestation as the ordering/treating clinician — coders cannot infer a UCD diagnosis from lab results alone per the ICD-10-CM Official Coding Guidelines, Section I.B.
Which Diagnostic or Lab Results Support This Code?
Supporting findings that strengthen the clinical basis for E72.20 include:
- Elevated plasma ammonia (hyperammonemia) confirmed on quantitative testing
- Plasma amino acid panel showing elevated glutamine, alanine, or ornithine with reduced citrulline — consistent with a proximal urea cycle block
- Urine organic acid analysis or urine orotic acid levels (elevated in OTC deficiency; normal/low in CPS1)
- Genetic sequencing panel ordered but results pending at time of encounter
- Brain MRI findings consistent with hyperammonemic encephalopathy (if applicable)
What Is the Documentation Standard for Inpatient vs. Outpatient Settings?
| Setting | Key Documentation Rule |
|---|---|
| Inpatient | Code the condition to the highest degree of certainty at discharge; if enzyme is still unspecified at discharge, E72.20 is appropriate as principal or secondary |
| Outpatient | Code only confirmed diagnoses; “rule out” or “suspected” UCD cannot be coded — the presenting sign or symptom (e.g., R79.89 for hyperammonemia) should be used until confirmed |
How Does E72.20 Affect Medical Billing and Claims?
E72.20 carries Complication and Comorbidity (CC) status in the MS-DRG system, which means its presence as a secondary diagnosis can increase the DRG weight and, accordingly, reimbursement for inpatient stays — provided the primary diagnosis is not in the exclusion list for this CC pairing.
Key billing considerations:
- Confirm CC eligibility against the current CMS MS-DRG v43.0 exclusion table before relying on the CC designation for DRG optimization
- E72.20 maps to MDC 10 (Endocrine, Nutritional and Metabolic Diseases and Disorders) for DRG grouping purposes
- For outpatient claims, ensure the diagnosis is confirmed — submitting E72.20 for a “suspected” or “rule-out” UCD in an outpatient setting is a compliance violation
- Electronic claim submission: omit the decimal point (submit as E7220 not E72.20) per standard 837P/837I transaction formatting
What CPT or Procedure Codes Are Commonly Billed With E72.20?
| CPT Code | Description | Typical Pairing Context |
|---|---|---|
| 82040 | Albumin, serum | Nutritional monitoring in UCD management |
| 82247 | Bilirubin, total | Liver function monitoring |
| 82570 | Creatinine, urine | Renal function in hyperammonemia workup |
| 83605 | Lactate (lactic acid) | Differential for metabolic acidosis vs. alkalosis |
| 84132 | Potassium | Electrolyte panel during hyperammonemic crisis |
| 81479 | Unlisted molecular pathology procedure | Genetic enzyme panel (when no specific CPT exists) |
| 96372 | Therapeutic injection (IM/subcutaneous) | Administration of nitrogen scavenger medications |
| 99233–99255 | Subsequent hospital care / consult | Inpatient management of hyperammonemic crisis |
Are There Any Prior Authorization or Coverage Restrictions?
- Nitrogen scavenger therapies (e.g., sodium phenylbutyrate, glycerol phenylbutyrate) billed alongside E72.20 frequently require prior authorization from commercial payers and Medicaid managed care plans
- Genetic testing (CPT 81479 or specific gene panels) may require documentation of clinical indication; payer LCDs vary significantly
- Medicare: UCD is predominantly a pediatric condition, but adult-onset or late-presenting cases exist — verify beneficiary eligibility and applicable LCD at the MAC level
- Some payers require a metabolic specialist attestation before approving high-cost enzymatic therapies linked to this diagnosis
What Coding Errors Should You Avoid With E72.20?
Coders applying E72.20 should be aware of the following high-risk mistakes, ranked by audit frequency:
- Using E72.20 when a specific subcode is supported — if OTC deficiency is documented, E72.21 is required; using E72.20 constitutes under-coding
- Coding E72.20 from lab results alone — hyperammonemia noted on a lab report does not permit a UCD diagnosis; provider documentation of the underlying condition is required
- Reporting E72.20 with E72.4 simultaneously — a Type 1 Excludes violation; HHH syndrome is a distinct entity that cannot co-exist with E72.20 on the same claim
- Applying E72.20 to a neonate with transient hyperammonemia — transient neonatal hyperammonemia codes to P74.6; E72.20 requires a confirmed congenital enzymatic defect
- Failing to update specificity after genetic results return — E72.20 used as a placeholder is appropriate temporarily, but not updating to a specific code once the enzyme defect is confirmed creates audit exposure
What Do Auditors Look for When Reviewing Claims With E72.20?
- Discrepancy between E72.20 and enzyme-specific language present elsewhere in the record
- Missing provider attestation linking hyperammonemia to an underlying urea cycle disorder
- Simultaneous reporting of excluded codes (E72.4 or P74.6)
- Absence of clinical documentation supporting the chronic/congenital nature of the disorder
- Use of E72.20 repeatedly across multiple encounters without any progression toward a specific diagnosis
How Does E72.20 Relate to Other ICD-10 Codes?
| Related Code | Relationship Type | Key Distinction |
|---|---|---|
| E72.21 | Sibling (more specific) | OTC deficiency — use when enzyme identified |
| E72.22 | Sibling (more specific) | CPS1 deficiency — autosomal recessive |
| E72.23 | Sibling (more specific) | Argininosuccinic aciduria |
| E72.29 | Sibling (other specified) | Named enzyme not listed in E72.21–E72.23 |
| E72.4 | Excludes1 — never code together | HHH syndrome — distinct disorder |
| P74.6 | Excludes1 — never code together | Transient neonatal hyperammonemia |
| R79.89 | Sign/symptom | Use for outpatient “suspected” UCD (unconfirmed) |
| E72.01–E72.09 | Adjacent category | Disorders of amino-acid transport — different metabolic pathway |
| Z84.89 | Family history | Family history of metabolic disease — supplemental |
What Is the Correct Code Sequencing When E72.20 Appears With Other Diagnoses?
- If E72.20 is the reason for the encounter (e.g., hyperammonemic crisis admission), sequence it as the principal diagnosis.
- If the patient is admitted for a complication of UCD (e.g., metabolic encephalopathy G92.8 or seizures G40.–), sequence the complication first and E72.20 as the secondary etiology code per the etiology/manifestation convention.
- Add any applicable “use additional code” codes for associated manifestations — for example, metabolic encephalopathy or intellectual disability if documented as related to the UCD.
- When dietary management is a focus of the encounter, add Z71.3 (Dietary counseling and surveillance) as an additional code.
Real-World Coding Scenario — How E72.20 Is Applied in Practice
A 14-month-old male is admitted to the pediatric unit following three days of progressive lethargy, irritability, and refusal to eat. Plasma ammonia returns at 320 µmol/L (reference < 50). The attending metabolic specialist documents: “Patient presents with hyperammonemic encephalopathy in the setting of a urea cycle disorder. Plasma amino acid panel is consistent with a proximal urea cycle defect; genetic enzyme panel has been sent and is pending. Starting sodium phenylacetate-sodium benzoate infusion and dietary protein restriction.”
Correct Code Application
- Primary diagnosis: E72.20 — Disorder of urea cycle metabolism, unspecified (UCD confirmed; enzyme pending)
- Secondary: G92.8 — Other toxic encephalopathy (hyperammonemic encephalopathy, as documented)
- Additional: Z71.3 — Dietary counseling and surveillance
Rationale: The physician explicitly confirms a UCD as the underlying etiology. E72.20 is appropriate because the specific enzyme has not yet been identified; the encounter is coded to the highest degree of certainty at the time of documentation.
Common Mistake in This Scenario
- Incorrect approach: Coding only R79.89 (Other specified abnormal findings of blood chemistry) for the hyperammonemia without capturing the underlying UCD
- Why it fails: The provider has confirmed a UCD diagnosis — this is no longer a sign or symptom encounter. Using only the lab finding code misrepresents the clinical picture, loses the CC designation for the admission, and may trigger a medical necessity query from the payer
Frequently Asked Questions About ICD-10 Code E72.20
Is ICD-10 Code E72.20 Valid for Use in FY 2026?
ICD-10 code E72.20 is a valid, billable diagnosis code for fiscal year 2026, covering dates of service from October 1, 2025 through September 30, 2026. No changes to its description or validity status have been issued by CMS since the code was introduced in FY 2016. Coders should confirm code validity annually using the CMS ICD-10-CM tabular updates.
What Is the Difference Between E72.20 and E72.29?
E72.20 is used when the urea cycle disorder cannot be specified at all — the enzyme is unknown or not documented. E72.29 covers “other specified” urea cycle disorders where the specific enzyme defect is named (such as arginase deficiency or citrullinemia type II) but does not match one of the individually listed codes (E72.21–E72.23). The critical distinction is whether the record identifies a named enzyme defect; if it does, E72.20 is incorrect.
Can E72.20 Be Used as a Principal Diagnosis for an Inpatient Admission?
Yes. E72.20 may serve as the principal diagnosis when the urea cycle disorder is the condition established after study to be chiefly responsible for the admission. This most commonly occurs with hyperammonemic crises where the UCD is the driving etiology. If the patient is admitted for a manifestation of the UCD (e.g., seizures or encephalopathy), the manifestation codes first per the etiology/manifestation sequencing convention in the ICD-10-CM Official Coding Guidelines.
Does E72.20 Qualify as a Complication or Comorbidity (CC) for DRG Purposes?
E72.20 qualifies as a Complication and Comorbidity (CC) under CMS MS-DRG v43.0 when reported as a secondary diagnosis. This designation can increase DRG weight and reimbursement for inpatient encounters. However, CC status is subject to exclusion logic — coders should verify that the primary diagnosis does not appear on the CC exclusion list paired with E72.20, using the current CMS MS-DRG definitions manual.
Should I Use E72.20 or P74.6 for Hyperammonemia in a Newborn?
P74.6 (Transient hyperammonemia of newborn) is the correct code when a neonate presents with elevated ammonia levels that resolve without a confirmed congenital enzymatic defect. E72.20 should be used only when the provider has documented a confirmed congenital urea cycle disorder as the underlying cause — even if enzyme specificity is pending. These two codes carry a Type 1 Excludes relationship and must never be reported together on the same claim.
What Documentation Is Needed to Justify E72.20 Instead of Just Coding the Hyperammonemia?
The provider must explicitly document a urea cycle disorder as the confirmed underlying diagnosis — not simply note elevated ammonia on a lab report. Per the ICD-10-CM Official Coding Guidelines, Section I.B, coders cannot assign a diagnosis code from laboratory findings alone without physician interpretation. A provider statement such as “disorder of urea cycle metabolism” or “inborn error of urea cycle” in the assessment is required before E72.20 can be assigned.
Key Takeaways
Every coder working with E72.20 should keep these points top of mind:
- E72.20 is the correct code only when a urea cycle disorder is confirmed but the specific enzyme defect is not identified in available documentation
- Before assigning E72.20, always review the record for enzyme-specific language that would require E72.21, E72.22, E72.23, or E72.29 instead
- Never report E72.20 alongside E72.4 (HHH syndrome) or P74.6 (transient neonatal hyperammonemia) — both carry Type 1 Excludes status
- In the outpatient setting, E72.20 requires a confirmed provider diagnosis — not a rule-out or suspected UCD
- E72.20 carries CC status in inpatient DRG grouping, making accurate assignment financially significant for hospital revenue cycle teams
- Provider query is appropriate — and encouraged — when the record contains hyperammonemia and metabolic findings consistent with UCD but lacks an explicit diagnostic statement
- Update specificity to a sub-code as soon as genetic or enzymatic test results are documented in the medical record to support diagnosis code specificity and reduce coding audit preparation risk
For additional guidance on metabolic disorder coding conventions, refer to ICD-10-CM Official Coding Guidelines Section I.C.4 (Endocrine, Nutritional and Metabolic Diseases) and the AHA Coding Clinic for any applicable UCD-specific guidance issued in recent editions.