PKU sphere™: A three month trial | Case Study
DESCRIPTION
A case study showcasing the results of a three-month trial of PKU sphereTM, assessing potential clinical benefits in comparison to taking an amino acid based protein substitute.
The patient was an adult male diagnosed with PKU on newborn screening. The patient attended the metabolic clinic reporting symptoms including fatigue and mild anxiety.
Relevant History
Dietary: Patient followed the low protein diet strictly during childhood, but in adulthood found adhering to protein substitutes and the low protein diet increasingly difficult.
Note:
This was not a controlled study and so it is not possible to demonstrate a causal relationship between the patient’s change in diet and improvement in self-reported symptoms.
In addition, this informal process of trialling a new product and recording several outcomes before and after was developed in conjunction with the patient. This was to support the case for access to his preferred protein substitute from his healthcare provider. This type of external motivation can sometimes affect results.
PKU sphere™ is a Food for Special Medical Purposes. All information is correct at the time of publishing (August 2020).
GMP-based protein substitutes were newly available and have been suggested to improve dietary adherence in adult PKU patients.(1,2)
Overall Aim
A three-month trial of PKU sphere was conducted to assess what (if any) clinical benefits were experienced by the patient, compared to when taking his usual amino acid-based protein substitute at baseline.
Dietetic Intervention
Assessments: All parameters were completed at baseline (whilst taking usual protein substitute) and after 3 months of PKU sphere intake including:
- Biochemical parameters: plasma phenylalanine: indicating metabolic control and vitamin B₁₂ and folate: indicating nutritional status.
- Dietary adherence and nutritional intake: dietary assessments completed by specialist metabolic dietitian.
- Psychosocial outcomes: Fatigue Severity Scale (3), SF-36 (4), assessing quality of life, cognitive failures questionnaire (5) assessing cognitive functioning, Hospital Anxiety and Depression Scale (6).
- Palatability and tolerance: self-reported by patient during dietary assessments.
| Parameter | Reference Range |
Baseline | Following 3 month trial |
Clinical Interpretation |
|---|---|---|---|---|
| Plasma phenylalanine (µmol/L) |
120 - 600 | 1297 | 560 | Clinically significant improvement |
| Plasma Vitamin B₁₂ (pg/mL)
|
197 - 771 | 264 | 416 | Clinically significant improvement |
| Plasma Folate (ng/mL) | 2.9 - 26.8 | 5.1 | 10.6 | Clinically significant improvement |
| Protein intake (g/day) | n/a | <0.5g/kg/day | >1g/kg/day | Clinically significant improvement |
| Fatigue Severity Scale | n/a | 22 | 12 | Clinically significant improvement |
| Quality of life (SF-36) | n/a | 88 (45th %ile) | 98 (75th %ile) | Stable |
| Cognitive failures questionnaire | n/a | 26/100 | 3/100 | Clinically significant improvement |
| Hospital Anxiety and Depression Scale | n/a | A - 9 (86th %ile, mild anxiety) D - 6 (64th %ile, normal range) |
A - 2 (18th %ile, normal range) D - 1 (28th %ile, normal range) |
Clinically significant improvement in anxiety symptoms |
The patient reported that PKU sphere was more palatable and tolerable compared to his previous amino acid-based protein substitute. This is undoubtedly important for patients who are expected to follow a restrictive and difficult lifelong diet to effectively manage their condition.
Overall, use of this product has allowed the patient to achieve considerably better metabolic control and achieve the target for phenylalanine recommended in European guidelines for PKU (7). His nutritional status has also improved, as evidenced by improvements in biochemical markers and dietary assessment of total protein intake.
The patient completed several validated, self-reported questionnaires to assess psychosocial outcomes (on advice from a neuropsychologist). All assessments revealed improvements in fatigue, quality of life, cognitive functioning and anxiety after taking PKU sphere for 3 months.
Following the 3 month trial, the patient continued to take PKU sphere. Bloodspot results remained much improved (655µmol/L and 475µmol/L) compared to their baseline plasma level (1297µmol/L) whilst taking the previous protein substitute. This demonstrated that the patient was able to achieve longer-term adherence, whilst taking PKU sphere as part of a therapeutic diet.
The data presented supports that PKU sphere improved clinical outcomes and dietary adherence for this patient, compared to when taking their previous amino acid-based protein substitute.
- van Calcar SC, MacLeod EL, Gleason ST, Etzel MR, Clayton MK, Wolff JA, et al. Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids. The American Journal of Clinical Nutrition. 2009;89(4):1068-77.
- Ney DM, Stroup BM, Clayton MK, Murali SG, Rice GM, Rohr F, et al. Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial. The American Journal of Clinical Nutrition. 2016.
- Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121-3.
- Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Medical care. 1992:473-83.
- Broadbent DE, Cooper PF, FitzGerald P, Parkes KR. The cognitive failures questionnaire (CFQ) and its correlates. British journal of clinical psychology. 1982;21(1):1-16.
- Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta psychiatrica scandinavica. 1983;67(6):361-70.
- van Spronsen FJ, van Wegberg AM, Ahring K, Bélanger-Quintana A, Blau N, Bosch AM, et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. The Lancet Diabetes & Endocrinology. 2017.
