Long-term follow-up of patients with phenylketonuria treated with tetrahydrobiopterin: a seven years experience

Orphanet Journal of Rare Diseases

Generoso Andria⁴  Giancarlo Parenti⁴  Pietro Strisciuglio⁴  Giuseppe Bonapace⁵  Aurora Daniele¹  Margherita Ruoppolo²  Brunella Capaldo⁶  Serena Paladino⁴  Carla Ungaro⁴  Anna Nastasi³  Roberto Della Casa⁴  Daniela Concolino⁵  Iris Scala⁴ 

[1] Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Seconda Università degli Studi di Napoli, Caserta, Italy;CEINGE-Biotecnologie Avanzate s.c.ar.l., Naples, Italy;Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University, Naples, Italy;Department of Translational Medicine-Section of Pediatrics, Federico II University, Via S. Pansini 5, Naples, 80131, Italy;Department of Pediatrics, Magna Graecia University, Catanzaro, Italy;Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy

关键词: Side effects;    Safety;    Tolerance;    Therapy;    Hyperphenylalaninemia;    Sapropterin;    Tetrahydrobiopterin;    Phenylketonuria;    Phenylalanine hydroxylase deficiency;   

Others  :  1135291
DOI  :  10.1186/s13023-015-0227-8

 received in 2014-10-24, accepted in 2015-01-15,  发布年份 2015

【 摘 要 】

Background

Phenylketonuria (PKU) is an autosomal recessive disorder caused by the deficiency of phenylalanine hydroxylase that catalyzes the conversion of phenylalanine to tyrosine, using tetrahydrobiopterin (BH4) as coenzyme. Besides dietary phenylalanine restriction, new therapeutic options are emerging, such as the treatment with BH4 in subgroups of PKU patients responding to a loading test with BH4.

Methods

A no-profit open-label interventional trial with long-term oral BH4 therapy, sponsored by the Italian Medicines Agency (AIFA), was performed in a group of 17 PKU patients resulted as BH4 responders among 46 subjects analyzed for BH4-responsiveness (prot. FARM5MATC7). We report on efficacy and safety data of BH4 therapy and analyze factors predicting BH4-responsiveness and long-term response to BH4. A BH4-withdrawal test was used as a proof of the efficacy of long-term therapy with BH4.

Results

Forty-four percent of the patients responded to the 48 h-long loading test with BH4. All the phenotypic classes were represented. Genotype was the best predictor of responsiveness, along with lower phenylalanine levels at diagnosis, higher tolerance and lower phenylalanine/tyrosine ratio before the test. In BH4 responder patients, long-term BH4 therapy resulted safe and effective in increasing tolerance while maintaining a good metabolic control. The BH4 withdrawal test, performed in a subset of patients, showed that improved tolerance was directly dependent on BH4 assumption. Tolerance to phenylalanine was re-evaluated in 43.5% of patients and was longitudinally analyzed in 5 patients.

Conclusions

Long-term treatment with BH4 is safe and effective in increasing tolerance to phenylalanine. There is real need to assess the actual tolerance to phenylalanine in PKU patients to ameliorate quality of life, improve nutritional status, avoiding unnecessarily restricted diets, and interpret the effects of new therapies for PKU.

【 授权许可】

   
2015 Scala et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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