Dataset Information

Differential diagnosis of progressive intellectual and neurological deterioration in children.

ABSTRACT:

Aim

To report the differential diagnosis in children with progressive intellectual and neurological deterioration (PIND) in the UK.

Method

Since 1997 the PIND Study has searched for variant Creutzfeldt-Jakob disease (vCJD) in children, using the British Paediatric Surveillance Unit to perform prospective surveillance of those younger than 16 years with PIND.

Results

From May 1997 to October 2019, 2255 children meeting PIND criteria had been notified, of whom 2008 (1085 males, 923 females) had underlying diagnoses. There were over 220 different diseases, including six cases of vCJD. The numbers presenting in four age groups were: <1 year, 805 (40%); 1 to 4 years inclusive, 825 (41%); 5 to 9 years inclusive, 264 (13%); and 10 to 15 years inclusive, 114 (6%). The two largest ethnic groups were White and Pakistani (58.2% and 17% of diagnosed cases). The most common diseases in these two ethnic groups are shown for the four age groups. The distribution of diseases varied with age but was quite similar in White and Pakistani children.

Interpretation

This paper provides a unique guide to the complex differential diagnosis of childhood PIND, showing considerable differences between four age groups, but similarities between ethnic groups. The PIND Study still provides the only systematic surveillance for vCJD in children in the UK.

What this paper adds

The prevalence of diseases causing childhood progressive intellectual and neurological deterioration in the UK is low (approximately 0.1/1000 live births). There were more than 220 different disorders, mainly genetically determined. The majority of disorders presented early in childhood: 81% before the age of 5 years. There were similarities in the disease spectrum in White and Pakistani children.

SUBMITTER: Verity C

PROVIDER: S-EPMC7891454 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential diagnosis of progressive intellectual and neurological deterioration in children.

Verity Christopher C Baker Elaine E Maunder Polly P Pal Suvankar S Winstone Anne Marie AM

Developmental medicine and child neurology 20200924 3

<h4>Aim</h4>To report the differential diagnosis in children with progressive intellectual and neurological deterioration (PIND) in the UK.<h4>Method</h4>Since 1997 the PIND Study has searched for variant Creutzfeldt-Jakob disease (vCJD) in children, using the British Paediatric Surveillance Unit to perform prospective surveillance of those younger than 16 years with PIND.<h4>Results</h4>From May 1997 to October 2019, 2255 children meeting PIND criteria had been notified, of whom 2008 (1085 male ...[more]

PMID: 32970345

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Project description:Background: Progressive intellectual and neurological deterioration (PIND) is a rare but severe childhood disorder characterized by loss of intellectual or developmental abilities, and requires quick diagnosis to ensure timely treatment to prevent possible irreversible neurological damage. Inborn errors of metabolism (IEMs) constitute a group of more than 1,000 monogenic conditions in which the impairment of a biochemical pathway is intrinsic to the pathophysiology of the disease, resulting in either accumulation of toxic metabolites and/or shortage of energy and building blocks for the cells. Many IEMs are amenable to treatment with the potential to improve outcomes. With this literature review we aim to create an overview of IEMs presenting with PIND in children, to aid clinicians in accelerating the diagnostic process. Methods: We performed a PubMed search on IEMs presenting with PIND in individuals aged 0-18 years. We applied stringent selection criteria and subsequently derived information on encoding genes, pathways, clinical and biochemical signs and diagnostic tests from IEMbase (www.iembase.org) and other sources. Results: The PubMed search resulted in a total of 2,152 articles and a review of references added another 19 articles. After applying our selection criteria, a total of 85 IEMs presenting with PIND remained, of which 57 IEMs were reported in multiple unrelated cases and 28 in single families. For 44 IEMs (52%) diagnosis can be achieved through generally accessible metabolic blood and urine screening tests; the remainder requires enzymatic and/or genetic testing. Treatment targeting the underlying pathophysiology is available for 35 IEMs (41%). All treatment strategies are reported to achieve stabilization of deterioration, and a subset improved seizure control and/or neurodevelopment. Conclusions: We present the first comprehensive overview of IEMs presenting with PIND, and provide a structured approach to diagnosis and overview of treatability. Clearly IEMs constitute the largest group of genetic PIND conditions and have the advantage of detectable biomarkers as well as amenability to treatment. Thus, the clinician should keep IEMs at the forefront of the diagnostic workup of a child with PIND. With the ongoing discovery of new IEMs, expanded phenotypes, and novel treatment strategies, continuous updates to this work will be required.

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Dataset Information

Differential diagnosis of progressive intellectual and neurological deterioration in children.

Aim

Method

Results

Interpretation

What this paper adds

Publications

Differential diagnosis of progressive intellectual and neurological deterioration in children.

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