Neurological deterioration in adult phenylketonuria

Weglage, Josef; Oberwittler, C.; Marquardt, Thorsten; Schellscheidt, J.; Teeffelen-Heithoff, A. van; Koch, Gilbert; Gerding, H.

doi:10.1023/a:1005607115309

Cited by 29 publications

(6 citation statements)

References 3 publications

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“…PKU is mainly a childhood disorder, but in rare cases, the first symptoms occur in adulthood, as in this case, mimicking other neurological conditions [ 7 , 8 ]. A few patients with adult-onset untreated PKU are reported in the literature [ 9 ]; most of these patients, including ours, show a MRI cerebral leukodystrophy pattern. The importance of considering PKU in case of an adult-onset leukodystrophy stems from the availability of an effective treatment, even in late-diagnosed cases.…”

Section: Discussionmentioning

confidence: 91%

Triple Genetic Diagnosis in a Patient with Late-Onset Leukodystrophy and Mild Intellectual Disability

Pasquetti,

Gazzellone,

Rossi

et al. 2023

IJMS

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We describe the complex case of a 44-year-old man with polycystic kidney disease, mild cognitive impairment, and tremors in the upper limbs. Brain MRI showed lesions compatible with leukodystrophy. The diagnostic process, which included clinical exome sequencing (CES) and chromosomal microarray analysis (CMA), revealed a triple diagnosis: autosomal dominant polycystic kidney disease (ADPKD) due to a pathogenic variant, c.2152C>T-p.(Gln718Ter), in the PKD1 gene; late-onset phenylketonuria due to the presence of two missense variants, c.842C>T-p.(Pro281Leu) and c.143T>C-p.(Leu48Ser) in the PAH gene; and a 915 Kb duplication on chromosome 15. Few patients with multiple concurrent genetic diagnoses are reported in the literature; in this ADPKD patient, genome-wide analysis allowed for the diagnosis of adult-onset phenylketonuria (which would have otherwise gone unnoticed) and a 15q11.2 duplication responsible for cognitive and behavioral impairment with incomplete penetrance. This case underlines the importance of clinical genetics for interpreting complex results obtained by genome-wide techniques, and for diagnosing concurrent late-onset monogenic conditions.

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Section: Discussionmentioning

confidence: 91%

Triple Genetic Diagnosis in a Patient with Late-Onset Leukodystrophy and Mild Intellectual Disability

Pasquetti,

Gazzellone,

Rossi

et al. 2023

IJMS

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“…Delayed diagnosis of PKU presenting with neurological dysfunction like spastic paraparesis, dementia and mental retardation has been reported. 9,10,11,12 To the best of our knowledge this is the first ever case report, with simultaneous, delayed adult diagnosis of PKU in two members of the same family. Significant difference in phenotype is well documented in untreated classical PKU patients with only subtle learning difficulties in 10% of patients.…”

Section: Discussionmentioning

confidence: 92%

Delayed diagnosis of phenylketonuria – a case report of two siblings

et al. 2013

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Phenylketonuria (PKU), is an autosomal recessive condition affecting the amino acid metabolism. The UK National newborn screening programme was commenced in 1969 and PKU is one among the five conditions included in the screening programme. We present the case history of two siblings of a family with a delayed diagnosis of PKU. This case history highlights such an occurrence. PKU should be considered as an important differential in the diagnosis of adult patients with learning difficulties, seizures and behavioural problems. It would be prudent to instigate plasma and urine amino/organic acid analyses in adult patients with unexplained neuropsychological manifestations.

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“…We reviewed the literature and found eight published cases of PKU presenting in adulthood (online supplemental table 1). 4 7–13 The majority presented with spastic paraparesis, cognitive decline and visual disturbance, with confluent white matter abnormalities on MR brain imaging. Our patient, and half the case reports identified, were described as having a background of learning difficulties or low academic attainment.…”

Section: Discussionmentioning

confidence: 99%

A treatable inborn error of metabolism presenting in the sixth decade

Martin,

Davidson,

Murdoch

et al. 2024

BMJ Case Rep

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Phenylketonuria (PKU) is an inborn error of amino acid metabolism. If untreated, PKU can result in global developmental delay, learning difficulties or seizures. For that reason, PKU is included in the UK neonatal screening programme. We describe a patient in his sixth decade presenting with progressive cognitive decline and spasticity, in whom a diagnosis of PKU was eventually reached. We note that although we currently have a robust neonatal screening programme, this has not always been the case. Patients born before 1969 were not screened, and tests used in early screening programmes were less sensitive than those used today. This case serves as a reminder that inherited metabolic disorders may present in later life and may mimic the neurocognitive and radiological picture of other white matter syndromes.

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Neurological deterioration in adult phenylketonuria

Cited by 29 publications

References 3 publications

Triple Genetic Diagnosis in a Patient with Late-Onset Leukodystrophy and Mild Intellectual Disability

Triple Genetic Diagnosis in a Patient with Late-Onset Leukodystrophy and Mild Intellectual Disability

Delayed diagnosis of phenylketonuria – a case report of two siblings

A treatable inborn error of metabolism presenting in the sixth decade

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