Dr. Louis Isaac Woolf: At the Forefront of Newborn Screening and the Diet to Treat Phenylketonuria—Biography to Mark His 100th Birthday †

Fernández, J.R. Alonso

doi:10.3390/ijns6030061

Cited by 5 publications

(8 citation statements)

References 22 publications

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“…The idea of a diet as a possible treatment for PKU was not new, but discussions in the 1930s had questioned whether the presumed biochemical abnormality was the cause of the clinical features in PKU, and whether a nutritionally adequate diet could be produced if phenylalanine was removed [ 25 , 26 ]. In the early 1950s, Dr. Louis Woolf, a chemist at Great Ormond Street Hospital, London [ 7 , 27 ], tried supplementing the diet of two infants with PKU with glutamic acid, hoping to reduce their blood phenylalanine concentrations by increasing its excretion. Blood phenylalanine was not lowered and there was no benefit to the children’s development.…”

Section: Dietary Treatment Of Pku—the Prototypementioning

confidence: 99%

“…Bickel, Gerrard and Hickmans were awarded the John Scott Award for the discovery of the dietary treatment [ 48 , 49 ] ( Figure 7 ). In 2019, the International Society for Neonatal Screening awarded Dr. Louis Woolf a plaque to recognize his contribution [ 5 , 7 , 50 ].…”

Section: Recognitionmentioning

confidence: 99%

“…The idea of a special diet for the treatment of PKU was not new, and of particular importance in the history is the contribution made by Dr. Louis Woolf. The ideas he shared freely with the Birmingham team in their development of the first diet have been recently documented in publications to mark his 100th birthday [ 5 , 6 , 7 ], and with his help, a prototype diet was attempted in Birmingham for the treatment of a two-year-old girl, Sheila Jones. The three professionals directly involved in the manufacture and application of the diet were pioneers, without whom the story of PKU would have been very different.…”

Section: Introductionmentioning

confidence: 99%

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The First Treatment for PKU: The Pioneers—Birmingham 1951

Green

2021

IJNS

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Prior to the introduction of newborn screening, Phenylketonuria (PKU) was a devastating disorder with affected individuals usually committed to a life in care in large institutions (asylums). Newborn screening only began after it was shown that those with PKU could be treated with a modified diet and could subsequently lead normal lives. The first production of a diet and the demonstration of its effectiveness was thus a key milestone in the history of both PKU and newborn screening, and took place in Birmingham, UK, in 1951. The pioneers were a two-year-old girl called Sheila Jones, her mother Mary, and three dedicated professionals at Birmingham Children’s Hospital: Evelyn Hickmans, John Gerrard and Horst Bickel. Together, they changed the course of PKU for those across the world. This review summarises the history and achievements of this team who opened the door to PKU treatment and the introduction of newborn screening.

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Section: Dietary Treatment Of Pku—the Prototypementioning

confidence: 99%

Section: Recognitionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The First Treatment for PKU: The Pioneers—Birmingham 1951

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2021

IJNS

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“…Følling concluded that this secondary metabolite was derived from dietary phenylalanine, and later the condition was lately named [ 16 ]. PKU was first treated through dietary control in the 1950s, and then, in 1963, population-based newborn screening using dried blood spot (DBS) testing was introduced to assess Phe concentration [ 17 ], enabling early diagnosis and initiation of treatment.…”

Section: Introductionmentioning

confidence: 99%

Genetic etiology and clinical challenges of phenylketonuria

et al. 2022

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This review discusses the epidemiology, pathophysiology, genetic etiology, and management of phenylketonuria (PKU). PKU, an autosomal recessive disease, is an inborn error of phenylalanine (Phe) metabolism caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene. The prevalence of PKU varies widely among ethnicities and geographic regions, affecting approximately 1 in 24,000 individuals worldwide. Deficiency in the PAH enzyme or, in rare cases, the cofactor tetrahydrobiopterin results in high blood Phe concentrations, causing brain dysfunction. Untreated PKU, also known as PAH deficiency, results in severe and irreversible intellectual disability, epilepsy, behavioral disorders, and clinical features such as acquired microcephaly, seizures, psychological signs, and generalized hypopigmentation of skin (including hair and eyes). Severe phenotypes are classic PKU, and less severe forms of PAH deficiency are moderate PKU, mild PKU, mild hyperphenylalaninaemia (HPA), or benign HPA. Early diagnosis and intervention must start shortly after birth to prevent major cognitive and neurological effects. Dietary treatment, including natural protein restriction and Phe-free supplements, must be used to maintain blood Phe concentrations of 120–360 μmol/L throughout the life span. Additional treatments include the casein glycomacropeptide (GMP), which contains very limited aromatic amino acids and may improve immunological function, and large neutral amino acid (LNAA) supplementation to prevent plasma Phe transport into the brain. The synthetic BH4 analog, sapropterin hydrochloride (i.e., Kuvan®, BioMarin), is another potential treatment that activates residual PAH, thus decreasing Phe concentrations in the blood of PKU patients. Moreover, daily subcutaneous injection of pegylated Phe ammonia-lyase (i.e., pegvaliase; PALYNZIQ®, BioMarin) has promised gene therapy in recent clinical trials, and mRNA approaches are also being studied.

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“…Currently, the only treatment available for all PKU patients in the UK is a lifelong phe restricted diet. This diet was first conceptualised by Professor Isaac Woolf using casein hydrolysate treated with active carbon to produce a dietary supplement low in Phe [ 4 ]. Woolf worked with Dr Horst Bickel to treat the first patient with this diet at Birmingham Children's Hospital [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Mental health diagnoses in adults with phenylketonuria: a retrospective systematic audit in a large UK single centre

Altman

Hussain

Green

et al. 2021

Orphanet J Rare Dis

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Background Recently published European Society for Phenylketonuria (ESPKU) guidelines have recommended a lifelong diet with phenylalanine (Phe) control ≤ 600 μmol/L for phenylketonuria (PKU) patients. This study aimed to identify whether PKU adult patients are at a higher risk of mental health diagnoses if their 2-year average Phe level is higher than the ESPKU European guidelines. Published studies identified by a literature review showed that related studies have been published in American and European PKU study populations but not in the United Kingdom (UK) study populations. Previous studies also involved a smaller number of participants due to this being a rare disease. Results We undertook a retrospective audit at a single large PKU centre in the UK. 244 adult PKU patients at the centre were included, 220 of which had a recorded Phe level. Approximately 75% of the patients in this study did not meet the ESPKU European guidelines for Phe control. A systematic search of the electronic patient record was undertaken looking for mental health diagnoses. Compared to two-year average Phe levels ≤ 600 μmol/L, PKU adult patients with two-year average Phe levels > 600 μmol/L were more likely to have diagnoses of low mood, depression, anxiety, or mood swings, but only low mood reached statistical significance (p < 0.05). Conclusions PKU patients with two-year average Phenylalanine levels greater than ESPKU guidelines may be at greater risk of mental health diagnoses and symptoms. Many of these adult PKU patients will be lost to follow-up, and therefore may be receiving treatment for mental health conditions in the community. Multicentre UK studies and international collaborations are required to overcome low participant numbers in the study of this rare disease.

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Dr. Louis Isaac Woolf: At the Forefront of Newborn Screening and the Diet to Treat Phenylketonuria—Biography to Mark His 100th Birthday †

Abstract: * Retired [...]

Cited by 5 publications

References 22 publications

The First Treatment for PKU: The Pioneers—Birmingham 1951

The First Treatment for PKU: The Pioneers—Birmingham 1951

Genetic etiology and clinical challenges of phenylketonuria

Mental health diagnoses in adults with phenylketonuria: a retrospective systematic audit in a large UK single centre

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