Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey

peer reviewedMany countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. © 2021 The Author

Ketogenic diet for mitochondrial disease: a systematic review on efficacy and safety

BACKGROUND: No curative therapy for mitochondrial disease (MD) exists, prioritizing supportive treatment for symptom relief. In animal and cell models ketones decrease oxidative stress, increase antioxidants and scavenge free radicals, putting ketogenic diets (KDs) on the list of management options for MD. Furthermore, KDs are well-known, safe and effective treatments for epilepsy, a frequent symptom of MD. This systematic review evaluates efficacy and safety of KD for MD. METHODS: We searched Pubmed, Cochrane, Embase and Cinahl (November 2020) with search terms linked to MD and KD. From the identified records, we excluded studies on Pyruvate Dehydrogenase Complex deficiency. From these eligible reports, cases without a genetically confirmed diagnosis and cases without sufficient data on KD and clinical course were excluded. The remaining studies were included in the qualitative analysis. RESULTS: Only 20 cases (14 pediatric) from the 694 papers identified met the inclusion criteria (one controlled trial (n��= 5), 15 case reports). KD led to seizure control in 7 out of 8 cases and improved muscular symptoms in 3 of 10 individuals. In 4 of 20 cases KD reversed the clinical phenotype (e.g. cardiomyopathy, movement disorder). In 5 adults with mitochondrial DNA deletion(s) related myopathy rhabdomyolysis led to cessation of KD. Three individuals with POLG mutations died while being on KD, however, their survival was not different compared to individuals with POLG mutations without KD. CONCLUSION: Data on efficacy and safety of KD for MD is too scarce for general recommendations. KD should be considered in individuals with MD and therapy refractory epilepsy, while KD is contraindicated in mitochondrial DNA deletion(s) related myopathy. When considering KD for MD the high rate of adverse effects should be taken into account, but also spectacular improvements in individual cases. KD is a highly individual management option in this fragile patient group and requires an experienced team. To increase knowledge on this-individually-promising management option more (prospective) studies using adequate outcome measures are crucial

High energy expenditure in a patient with feeding problems and Noonan syndrome spectrum disorder

Feeding problems are present in more than 50% of patients with a Noonan syndrome spectrum disorder in the first years of life. Food intake problems like severe or frequently vomiting may not only affect growth and development, but may also influence the process of learning how to eat and can have a great impact on the whole family. In addition to food intake problems, there is growing evidence that patients with a Noonan syndrome spectrum disorder may have a lower body mass index (BMI) due to a high energy expenditure, although little is known about the actual energy intake patients with a Noonan syndrome spectrum disorder need to maintain a healthy BMI. This article illustrates the challenge to recognise a high energy expenditure especially when a patient frequently vomits. Multidisciplinary attention is needed to manage food intake, vomiting and energy expenditure problems in patients with a Noonan syndrome spectrum disorder

Can untreated PKU patients escape from intellectual disability? A systematic review

PubMedID: 30157945Background: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients. Methods: To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ?1200 µmol/l; and 3) IQ ?80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers. Results: In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms. Conclusions: Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients. © 2018 The Author(s)

Dietary practices in propionic acidemia: A European survey

Contains fulltext : 181525.pdf (publisher's version ) (Open Access

Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra

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'Bahasa tak sama dengan agama'

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Key European guidelines for the diagnosis and management of patients with phenylketonuria

We developed European guidelines to optimise phenylketonuria (PKU) care. To develop the guidelines, we did a literature search, critical appraisal, and evidence grading according to the Scottish Intercollegiate Guidelines Network method. We used the Delphi method when little or no evidence was available. From the 70 recommendations formulated, in this Review we describe ten that we deem as having the highest priority. Diet is the cornerstone of treatment, although some patients can benefit from tetrahydrobiopterin (BH4). Untreated blood phenylalanine concentrations determine management of people with PKU. No intervention is required if the blood phenylalanine concentration is less than 360 mumol/L. Treatment is recommended up to the age of 12 years if the phenylalanine blood concentration is between 360 mumol/L and 600 mumol/L, and lifelong treatment is recommended if the concentration is more than 600 mumol/L. For women trying to conceive and during pregnancy (maternal PKU), untreated phenylalanine blood concentrations of more than 360 mumol/L need to be reduced. Treatment target concentrations are as follows: 120-360 mumol/L for individuals aged 0-12 years and for maternal PKU, and 120-600 mumol/L for non-pregnant individuals older than 12 years. Minimum requirements for the management and follow-up of patients with PKU are scheduled according to age, adherence to treatment, and clinical status. Nutritional, clinical, and biochemical follow-up is necessary for all patients, regardless of therapy