Latest Review Date: February 2024

Category:  Medicine                                                     

POLICY:

Effective for dates of service March 1, 2023 and after:

Nutritional treatment of certain medical conditions and chronic diseases may be considered medically necessary when the following criteria are met:

1. The appropriate diagnosis is confirmed by testing and is documented in the medical record.
2. The individual will sustain severe health complications or will not survive without this nutritional treatment.
3. The nutritional treatment is prescribed by a physician and monitored by a physician and/or a clinical nutritionist.
4. The product must be labeled for the dietary management of a specific medical disorder, disease, or condition for which there are distinctive nutritional requirements.

Examples of medical conditions that require special dietary intervention may include the following:

• Chylous Effusion
• Cystic Fibrosis
• Cystinosis
• Disorders of leucine metabolism
• Eosinophilic Esophagitis*
• Epilepsy
• Exocrine pancreatic insufficiency
• Galactosemia
• Glutaric Acidemia (Types I and II)
• Glycogen Storage Disease
• Hereditary Fructose Intolerance
• Homocystinuria
• Isovaleric acidemia
• Long Chain Acyl Co A Dehydrogenase Deficiency (LCHAD)
• Maple Syrup Urine Disease
• Methylmalonic Acidemia
• Mitochondrial fatty acid oxidation defects
• Partial villus atrophy due to food protein sensitivity
• Phenylketonuria (PKU)***
• Phosphoenolpyruvate carboxykinase deficiency
• Propionic Acidemia
• Pyruvate dehydrogenase complex deficiency
• Tyrosinemia Types I and II
• Urea Cycle Disorders

*This condition may be covered for an amino acid-based elemental formula (e.g. Elecare or Neocate) up to 1 year of age, if the following criteria are documented in the medical record:

1. The diagnosis is biopsy-proven.
2. The individual has persistent GI symptoms including nausea, vomiting, diarrhea, abdominal pain, dysphagia, weight loss, and/or failure to thrive.
3. The individual has failed an elimination diet or a hypoallergenic diet (e.g., Alimentum, Nutramigen, or Pregestimil).

***Nutritional supplements for phenylketonuria (PKU) (ICD-10 code E70.0) may be considered medically necessary throughout the lifespan of the patient.

Available medical foods for PKU may include but are not limited to the following:

The following medical conditions are considered not medically necessary for any type of formula or medical food supplement:

• Accentrate® for ADHD
• Asthma/wheezing
• Colic
• Cow’s milk protein allergy or intolerance
• Deplin® for Depression and Schizophrenia
• Eczema
• Eosinophilic Gastroenteritis
• Gastroesophageal reflux (GERD)
• Lactose intolerance
• Medical foods/Supplements for Mitochondrial Disease
• Metanx® and Posiapn® for Neuropathy
• Soy protein allergy or intolerance
• Theramine® for Chronic Pain
• Vayacog™ and Axona™ for Alzheimer’s
• Viral gastroenteritis
• VSL #3 for Irritable Bowel Syndrome

Medical food nutrients are special ordered through a pharmacy or pharmaceutical organization.

For dates of service prior to March 1, 2023:

Nutritional treatment of certain medical conditions and chronic diseases may be considered medically necessary when the following criteria are met:

1.      The appropriate diagnosis is confirmed by testing and is documented in the medical record.

2.      The individual will sustain severe health complications or will not survive without this nutritional treatment.

3.      The nutritional treatment is prescribed by a physician and monitored by a physician and/or a clinical nutritionist.

Some of the medical conditions that require special dietary intervention include the following:

• Phenylketonuria (PKU)***
• Cystinosis
• Cystic Fibrosis
• Chylous Effusion
• Epilepsy
• Homocystinuria
• Glutaric Acidemia (Types I and II)
• Disorders of leucine metabolism
• Isovaleric acidemia
• Maple Syrup Urine Disease
• Tyrosinemia Types I and II
• Urea Cycle Disorders
• Methylmalonic Acidemia
• Propionic Acidemia
• Glycogen Storage Disease
• Galactosemia
• Hereditary Fructose Intolerance
• Pyruvate dehydrogenase complex deficiency
• Phosphoenolpyruvate carboxykinase deficiency
• Mitochondrial fatty acid oxidation defects
• Partial villus atrophy due to food protein sensitivity
• Exocrine pancreatic insufficiency
• Long Chain Acyl Co A Dehydrogenase Deficiency (LCHAD)
• Eosinophilic Esophagitis*

*This condition may be covered for an amino acid-based elemental formula, such as Elecare or Neocate, up to age 1 year, if the following criteria are documented in the medical record:

1. The diagnosis is biopsy-proven.
2. The patient has persistent GI symptoms including nausea, vomiting, diarrhea, abdominal pain, dysphagia, weight loss, and/or failure to thrive.
3. The patient has failed an elimination diet or a hypoallergenic diet (e.g., Alimentum, Nutramigen, or Pregestimil).

***Nutritional supplements for phenylketonuria (PKU) (ICD-10 code E70.0) may be considered medically necessary throughout the lifespan of the patient.

The available medical foods for PKU may include:

• Phenyl Free 1
• Phenyl Free 2
• Phenyl Free 2 HP
• Milupa PKU-1
• Milupa PKU-2
• Milupa PKU-3
• Crystalline amino acid mix plus Protein Free Diet Powder
• Periflex
• X Phe Analog
• X Phe Maxamaid
• X Phe Maxamum
• Phenex-1
• Phenex-2
• Phlexy-10
• Phenylade Blend, PheBLOC tablets
• Lophlex
• Phlexy-Vits
• Add-Ins
• PhenylAde
• PKU Gel
• PKU Express
• PKU Cooler
• Camino Pro

The following medical conditions are considered not medically necessary for any type of formula or medical food supplement:

• Colic
• Gastroesophageal reflux (GERD)
• Cow’s milk protein allergy or intolerance
• Soy protein allergy or intolerance
• Lactose intolerance
• Viral gastroenteritis
• Eczema
• Asthma/wheezing
• Eosinophilic Gastroenteritis
• Metanx® and Posiapn® for Neuropathy
• Accentrate® for ADHD
• Deplin® for Depression and Schizophrenia
• Vayacog™ and Axona™ for Alzheimer’s
• Theramine® for Chronic Pain
• VSL #3 for Irritable Bowel Syndrome
• Medical foods/Supplements for Mitochondrial Disease

These medical food nutrients are not prescription drugs; they are, however, not products that one can walk into a drug store and purchase off the shelf. They must be special ordered through a pharmacy or pharmaceutical organization.

Exempt Infant Formulas Marketed in the United States by Manufacturer and Category (Content current as of: 12/03/2019)

• Verified January 2022-FDA end dated list 2019
• https://www.fda.gov/food/infant-formula-guidance-documents-regulatory-information/exempt-infant-formulas-marketed-united-states-manufacturer-and-category

DESCRIPTION OF PROCEDURE OR SERVICE:

There are many chronic diseases or conditions of childhood that require special dietary intervention. These diseases may be associated with increased nutritional requirements and metabolic demands or with decreased nutrient intakes, limitations of digestion and absorption, and/or increased nutrient losses.

Inborn Errors of Metabolism

There are metabolic diseases such as inborn errors of metabolism that have special nutritional needs resulting from genetic disorders of the digestive cycle. These disorders are treatable by dietary modifications, which can prevent complications like intellectual disabilities and death. The nutritional treatment may include restriction of one or more amino acids, restriction of total nitrogen, or the supplementation of specific substances. 

Inborn errors of metabolism are a group of rare disorders resulting in the excessive accumulation of an amino acid or other product along the metabolic pathway for lack of a natural enzyme required to digest certain foods. Manifestations of these disorders generally include central nervous system dysfunction, developmental delay, seizures and liver dysfunction.

Other metabolic diseases, such as disorders of carbohydrate metabolism, lipid metabolism, or vitamin or cofactor metabolism, may also benefit from dietary interventions. The treatment process should be monitored by a physician and a clinical nutritionist familiar with the particular disease. Each individual’s caloric and nutritional requirements should be determined.

Some medical conditions may require certain medications and/or a change in infant formula or nutrition for treatment. However, these conditions are usually not considered life-threatening conditions and may improve with time. These conditions include, but are not limited to, colic, gastroesophageal reflux disease (GERD), cow’s milk protein allergy, soy protein allergy, lactose intolerance, viral gastroenteritis, eczema, asthma/wheezing and eosinophilic gastroenteritis.

Eosinophilic Esophagitis (EE) 

Allergic eosinophilic gastroenteropathies are a group of heterogeneous disorders characterized by eosinophilic infiltration of the gut. The 2 main disorders are eosinophilic esophagitis (EE) and eosinophilic gastroenteritis (EG). Symptoms of these disorders are similar to those of other GI diseases and include nausea, vomiting, dysphagia, diarrhea, epigastric or abdominal pain, and poor weight gain. 

The diagnosis of eosinophilic esophagitis can only be made by endoscopy and biopsy. Eosinophilic esophagitis is an increasingly recognized cause of dysphagia and possibly heartburn that is unresponsive to anti-reflux measures. It is thought to be a chronic illness requires persistent dietary restrictions and/or consistent medication therapy. Treatment options include corticosteroids, acid suppression, dietary restriction, esophageal dilation to treat strictures or complete dietary elimination using an amino acid based formula.

Glycogen Storage Disease

Patients with Glycogen Storage Disease may experience hypoglycemia at night, which can lead to seizures, brain damage, and even death. Glycosade is a long-acting starch that allows patients to maintain a normal blood glucose level and avoid nighttime hypoglycemia. This supplement may be covered for a period of time with documentation that the patient’s symptoms have improved and the blood glucose levels are steady.

Phenylketonuria (PKU)

Classic phenylketonuria (PKU) is a rare metabolic disorder that usually results from a deficiency of a liver enzyme known as phenylalanine hydroxylase (PAH). This enzyme deficiency leads to elevated levels of the amino acid phenylalanine (Phe) in the blood and other tissues. Intellectual disabilities, microcephaly, delayed speech, seizures, eczema, behavior abnormalities and other symptoms characterize the untreated state. Approximately 1 of every 10,000 to 15,000 infants in the United States is born with PKU.

Dietary therapy with restriction of dietary PHE intake remains the mainstay of therapy for PAH deficiency, requiring a decrease in the intake of natural protein and replacing it with a protein (amino acid mixture) source devoid of PHE. An experienced metabolic physician and nutritionist team should manage this therapy. Because foods normally consumed as protein sources contain other essential nutrients, it is important that a diet modified for PAH deficiency provides sources for all other nutrients necessary for normal growth and health maintenance.

Implementing a Phe-restricted diet early in life can significantly reduce mental deficiencies associated with PKU. Metabolic control via medical nutrition therapy involves the use of medical foods including medical protein sources and modified low-protein products in addition to the provision of required amounts of Phe through small amounts of natural protein. The response is monitored throughout periodic measurement of blood Phe levels in conjunction with analysis of nutritional intake and review of nutritional status. Most experts advocate lifelong dietary treatment for metabolic control of blood Phe levels. Data suggest that elevated Phe levels in adolescents and adults adversely affect cognitive function and case reports have documented deterioration of adult patients with PKU after diet discontinuation. Women with PKU must also maintain strict metabolic control before and during pregnancy to prevent fetal damage. Metabolic control of PKU can be difficult to achieve, and poor control can result in significant decline of mental and behavioral performance.

KEY POINTS:

Not applicable.

KEY WORDS:

Childhood medical conditions, childhood chronic diseases, inborn errors of metabolism, nutritional treatment, exempt infant formula, Lipistart, Eosinophilic Esophagitis, GERD, Glycogen Storage Disease, cow’s milk protein allergy, colic, lactose intolerance, Phenylketonuria , PKU

Practice Guidelines and Position Statements

American College of Medical Genetics and Genomics

Dietary therapy with restriction of dietary PHE intake remains the mainstay of therapy for PAH deficiency, requiring a decrease in the intake of natural protein and replacing it with a protein (amino acid mixture) source devoid of PHE. An experienced metabolic physician and nutritionist team should manage this therapy.

APPROVED BY GOVERNING BODIES:

According to the Food and Drug Administration (FDA) (section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)) a product must meet all the following minimum criteria to be considered a medical food:

1. The product must be a food for oral or tube feeding.
2. The product must be labeled for the dietary management of a specific medical disorder, disease, or condition for which there are distinctive nutritional requirements.
3. The product must be used under the supervision of a physician.

U.S. Food and Drug Administration. Regulatory Information. Section 5 of Orphan Drug Act. Available at: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/MedicalFoods/default.htm.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan.  

CURRENT CODING:

HCPCS:             

REFERENCES:

1. American Academy of Pediatrics Committee on Nutrition. Reimbursement for medical foods for inborn errors of metabolism, Pediatrics, May 1994, Vol. 93, No. 5, p. 860.
2. Berry SA, Brown CS, Greene C, Camp KM, McDonough S, Bocchini JA Jr; Follow-up and Treatment (FUTR) Workgroup for the Advisory Committee on Heritable Disorders in Newborns and Children. Medical Foods for Inborn Errors of Metabolism: History, Current Status, and Critical Need. Pediatrics. 2020 Mar;145(3):e20192261. doi: 10.1542/peds.2019-2261. Epub 2020 Feb 7.
3. Berry SA, Christine S. Brown, Carol Greene, Kathryn M. Camp, Stephen McDonough, Joseph A. Bocchini, on behalf of the Follow-up and Treatment (FUTR) Workgroup for the Advisory Committee on Heritable Disorders in Newborns and Children; Medical Foods for Inborn Errors of Metabolism: History, Current Status, and Critical Need. Pediatrics March 2020; 145 (3): e20192261. 10.1542/peds.2019-2261.
4. Berry SA, Brown C, Grant M, et al. Newborn screening 50 years later: access issues faced by adults with PKU. Genet Med. 2013;15(8):591–599.
5. Camp KM, Lloyd-Puryear MA, Huntington KL. Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example. Mol Genet Metab. 2012;107(1–2):3–9.
6. Committee on Nutrition; Reimbursement for Medical Foods for Inborn Errors of Metabolism. Pediatrics May 1994; 93 (5): 860. 10.1542/peds.93.5.860
7. Enns, Gregory M and Pachman, Wendy. The adolescent with an inborn error of metabolism:  Medical issues and transition to adulthood, Adolescent Medicine, June 2002, Vol. 13, No. 2.
8. Howell R.R., et al. National institutes of health consensus development conference statement: Phenylketonuria: screening and management. Pediatrics, October 2001; 108: 4.
9. Liacouras CA. Eosinophilic esophagitis. Gastroenterology Clinics of North America 2008; 37: 989-998.
10. Liacouras CA. Eosinophilic esophagitis:  A 10 year experience in 381 children. Clinics of Gastroenterology and Hepatology 2005; 3(12): 1198-1206.
11. MacDonald, A., van Wegberg, A.M.J., Ahring, K. et al. PKU dietary handbook to accompany PKU guidelines. Orphanet J Rare Dis 15, 171 (2020). https://doi.org/10.1186/s13023-020-01391-y
12. Moats RA, Moseley KD, Koch R, and Nelson M, Jr. Brain phenylalanine concentrations in phenylketonuria: Research and treatment of adults. Pediatrics, December 2003; 112(6 Pt 2): 1575-9.
13. National Institutes of Health. Office of Dietary Supplements. Dietary Supplements for Primary Mitochondrial Disorders. https://ods.od.nih.gov/factsheets/PrimaryMitochondrialDisorders-HealthProfessional/
14. National Institutes of Health Consensus Development Panel. National Institutes of Health Consensus Development Conference Statement: phenylketonuria: screening and management, October 16-18, 2000. Pediatrics. 2001 Oct;108(4):972-82. doi: 10.1542/peds.108.4.972.
15. Reda SM. Gastrointestinal manifestations of food allergy.  Pediatric Health, September 2009, www.medscape.com/viewarticle/708187_print.
16. Rohr JF, Munier AW and Levy HL. Acceptability of a new modular protein substitute for the dietary treatment of phenylketonuria. Journal of Inherited Metabolic Disease, November 2001; 24(6): 623-30.
17. Schindeler S, Ghosh-Jerath S,Thompson S, et al. The effects of large neutral amino acid supplements in PKU: an MRS and neuropsychological study. Mol Genet Metab May 2007; 91(1): 48-54.
18. Spergel JM.  Nutritional management of eosinophilic esophagitis.  Gastrointestinal Endoscopy Clinics of North America 2008; 18(1): 179-194.
19. U.S. Food and Drug Administration. Regulatory Information. Section 5 of Orphan Drug Act. Available at: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/MedicalFoods/default.htm.
20. U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition.  Exempt infant formulas in the United States by manufacturer and category.  www.fda.gov/food/foodsafety/product-specificinformation/infantformula/guidanceregulatoryinformation/ucm106456.htm.
21. U.S. Food and Drug Administration .Orphan Drug Act - Relevant Excerpts https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/orphan-drug-act-relevant-excerpts
22. Vockley J, Andersson H, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. ACMG Practice Guidelines, August 2013; advance online publication 2 January 2014. doi:10.1038/gim.2013.157
23. Vockley J, Andersson HC, Antshel KM, et al; American College of Medical Genetics and Genomics Therapeutics Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188–200.

POLICY HISTORY:

Medical Policy Group, December 2004 (1)

Medical Policy Administration Committee, February 2005

Available for comment February 14-March 30, 2005

Medical Policy Group, July 2006 (1)

Medical Policy Group, December 2008 (1)

Medical Policy Group, April 2009 (1)

Medical Policy Group, October 2009 (3)

Medical Policy Administration Committee, November 2009

Available for comment November 6-December 21, 2009

Medical Policy Group, February 2010 (3)

Medical Policy Administration Committee, February 2010

Available for comment February 5-March 22, 2010

Medical Policy Group May 2011 (2): Updated Forms list to cover 1&2

Medical Policy Group, June 2012 (2): Updated Forms list, No policy changes

Medial Policy Administration Committee, July 2012

Medical Policy Group, June 2013 (2): Updated Forms list with two new FDA changes to Mead Johnson Nutrition section. No policy changes.

Medical Policy Group, November 2013 (2):  Added non-FDA approved Glycosade. No policy changes.

Medical Policy Group, January 2017 (6): Updated FDA exempt formula list, Description, Key Words and Governing Bodies. No change to policy statement.

Medical Policy Group, July 2018 (6): Updated FDA exempt formula list. No change to policy statement.

Medical Policy Group, October 2018 (6): Combined MP #029 Nutritional Supplements for Phenylketonuria (PKU). Updates to Description, Policy Statement, and References. Added Key Word “PKU”.

Medical Policy Group, December 2019 (6): Updates to Description, no change to policy intent.

Medical Policy Group, January 2021 (6): Updates to Description and Policy statement verbiage, no change to policy intent.

Medical Policy Group, February 2022 (6): Updates to Policy statement, expanded non-covered medical foods (previously non-covered per MP 495 Investigational Criteria), Description, Key Points, Governing Bodies, Practice Guidelines and References. No change to policy intent. Policy title change: Medical Foods and Specialized Formula for the Treatment of Inborn Errors of Metabolism.

Medical Policy Group, March 2023 (6): Updates to Policy statement to include addition of product requirement, Key Points, Governing Bodies and References. Draft period 3/1/23-4/15/23.

Medical Policy Administration Committee, March 2023.

Medical Policy Group, February 2024 (6): Updates to Description and References.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.