Patients with rare, brain-threatening disorder call on clinics to adopt first-ever treatment guidelines

Feb 04, 2014, 08:15 ET from Canadian PKU and Allied Disorders Inc.

- Canadian PKU and Allied Disorders encourages governments to fund PKU treatment tools as outlined by guidelines to improve outcomes in 2,000 Phenylketonuria patients -

TORONTO, Feb. 4, 2014 /CNW/ - Canadian PKU and Allied Disorders (CanPKU) is extremely pleased with the clinical practice guidelines designed for the rare, inherited brain-threatening metabolic disorder Phenylketonuria (PKU), affecting about 2,000 Canadians,  published online by the American College of Medical Genetics and Genomics (ACMG). The new set of guidelines for PKU, which was co-authored by two Canadian experts, support a comprehensive plan for early intervention and lifelong active treatment composed of a combination of therapies customized to the patient in order to minimize neurocognitive, psychiatric and physical symptoms of the disease.[i]  

"We congratulate the ACMG for establishing this critical guideline for PKU diagnosis and management, and call on all Canadian clinics to adopt this model," says John Adams, President and CEO of CanPKU, whose adult son has PKU. "These recommendations mirror our belief that all effective treatment tools for PKU must be made accessible to patients as a medical necessity, in order to allow optimal management of this devastating disease."

In PKU (also called phenylalanine hydroxylase deficiency or PAH deficiency), the body is unable to process an essential amino acid found in dietary protein, called phenylalanine (or "PHE"), and the resulting accumulation of PHE in the blood is toxic to the brain. If left untreated, symptoms can range from mild cognitive impairment to severe mental retardation with other neurological problems. As such, patients must adhere every day of their lives to a complicated and highly-restrictive low-protein diet to stave off the negative health consequences of PHE.

Despite patients' best efforts in dietary planning, adherence to the low-PHE diet and frequent blood monitoring, many are still unable to adequately control their blood PHE levels, leaving their brains at risk for neurocognitive impairment with psychosocial impacts.[ii] Though special low-protein medical foods can help patients adhere to the PHE-restricted diet, the first and only prescription medication for PKU, Kuvan (sapropterin dihydrochloride) is proven to reduce blood PHE levels when taken in conjunction with diet.[iii] The ACMG guidelines state that this "combination therapy" approach is likely to become the norm in treating PKU.

Guidelines advocate importance of treatments that reduce blood PHE levels
The ACMG recommendations reiterate that the maintenance of patients' blood PHE levels must be the goal of PKU therapies, and stress that these lifelong treatments are initiated as early in life as possible. The guidelines also stipulate that a reduction in blood PHE, as well as improvements in PHE tolerance and clinical symptoms, are all valid indications to continue a particular therapy. The ACMG guidelines advise that acceptable blood PHE levels for all patients should fall within the range of 120-360 μmol/l (2-6 mg/dl).

"The international clinician community acknowledges that PKU patients are unlikely to maintain appropriate PHE levels by simply adhering to diet alone, reaffirming the importance of access to all treatment tools," says Dr. Jerry Vockley, the Chief of Medical Genetics, Children's Hospital, University of Pittsburgh Medical Center, and Chair of the Therapeutics Committee with the ACMG. "PKU clinics have a responsibility to patients to provide a customized combination of therapies to improve a patient's blood PHE levels, and thereby improving health outcomes and quality of life."

Equitable access to treatments across Canada still needed
The ACMG guidelines call for PKU "treatment for life" mandates the need for health insurance to cover the cost of treatments including medications, regardless of the patient's age. Unfortunately, this is not the reality all Canadian PKU patients face, as access to publicly-funded treatments through provincial health  programs is varied – and therefore, inequitable. "There is not a single province that could not be doing a lot better for their residents living with PKU," says Mr. Adams.

While most Canadian provinces provide at least some form of coverage for medical foods, Kuvan – approved by Health Canada in 2010 – is only funded in Ontario[iv] and Saskatchewan,[v] as well as in Quebec on a case-by-case basis for women with PKU who are pregnant or plan to become pregnant.[vi] With no funding for Kuvan to date in B.C., Alberta, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia or P.E.I., this critical component of the recommended treatment regime for PKU is out of reach for most patients in Canada, exposing them to potential neurocognitive, psychiatric and physical symptoms caused by the disease.

"There is an immediate clinical need for equal access to combination therapy for PKU, including medical formulas, low protein foods and Kuvan. A harmonized approach to public funding for these treatments across the county will ensure PKU patients have the best possible care," says Dr. John Mitchell, ‎ pediatric endocrinologist at the Montreal Children's Hospital.  "The provinces must address the discrepancy in access to treatment to protect the brains of their constituents – be they children, teens or adults."

In addition to the ACMG guidelines, the Genetic Metabolic Dietitians International (GMDI) and the European Society for Phenylketonuria (E.S.PKU) have both recently called for improvements in global PKU management. Authors representing E.S.PKU published a pan-European patient and caregiver perspective on optimal care for PKU in Orphanet Journal of Rare Diseases, which insists that all aspects of treatment (dietary and pharmacologic) "should be reimbursed to ensure uniform access." [vii] The GMDI's nutrition guidelines for PKU endorse the diagnosis and treatment guidelines published by ACMG, and encourage an individualized treatment plan including Kuvan (for those who respond) and an appropriate combination of medical and modified low-protein foods. [viii]

About Canadian PKU and Allied Disorders Inc.
Canadian PKU and Allied Disorders Inc. is a non‐profit association of volunteers, dedicated to providing accurate news, information and support to families and professionals dealing with PKU and similar, rare, inherited metabolic disorders. Our mission is to improve the lives of people with PKU and allied disorders and the lives of their families. By allied disorders we mean other rare, inherited metabolic disorders also detected by newborn screening. For more information, visit and download our comprehensive resource for patients and families, PKU and the Brain.

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[i] Vockley, Andersson, Antshel et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline, Genetics in Medicine. 2014. doi:10-1038/gim.2013.57. Available at:
[ii] Brumm VL, Bilder D, Waisbren SE. Psychiatric symptoms and disorders in phenylketonuria.  Mol Genet Metab. 2010; 99:S59-S63
[iii] Kuvan [product monograph]. Toronto, ON: BioMarin Pharmaceutical (Canada) Inc.; 2010.
[iv] Ontario Ministry of Health and Long-Term Care. Formulary: Exceptional Access Program (EAP). Accessed on January 17, 2014. Available at:
[v] Saskatchewan Ministry of Health. Drug Plan and Extended Benefits Branch : Request for Kuvan®. Accessed on January 17, 2014. Available at:
[vi] Ajout aux listes de médicaments – Médicament d'exception [KUVAN]. Accessed on November 22, 2013. INESSS. Available at:
[vii] Hagedorn et al. Requirements for a minimum standard of care for phenylketonuria: the patients' perspective. Orphanet Journal of Rare Diseases 2013, 8:191.
[viii] Singh, Rohr, Frazier, etc al. Recommendations for the nutrition management of phenylalanine hydroxylase deficiency. Genetics in Medicine, 2014, doi:10.1038/gim.2013.179. Available at:


SOURCE Canadian PKU and Allied Disorders Inc.