Treatable inborn errors of metabolism presenting as cerebral palsy mimics: systematic literature review

Abstract

BackgroundInborn errors of metabolism (IEMs) have been anecdotally reported in the literature as presenting with features of cerebral palsy (CP) or misdiagnosed as ‘atypical CP’. A significant proportion is amenable to treatment either directly targeting the underlying pathophysiology (often with improvement of symptoms) or with the potential to halt disease progression and prevent/minimize further damage.MethodsWe performed a systematic literature review to identify all reports of IEMs presenting with CP-like symptoms before 5 years of age, and selected those for which evidence for effective treatment exists.ResultsWe identified 54 treatable IEMs reported to mimic CP, belonging to 13 different biochemical categories. A further 13 treatable IEMs were included, which can present with CP-like symptoms according to expert opinion, but for which no reports in the literature were identified. For 26 of these IEMs, a treatment is available that targets the primary underlying pathophysiology (e.g. neurotransmitter supplements), and for the remainder (n = 41) treatment exerts stabilizing/preventative effects (e.g. emergency regimen). The total number of treatments is 50, and evidence varies for the various treatments from Level 1b, c (n = 2); Level 2a, b, c (n = 16); Level 4 (n = 35); to Level 4–5 (n = 6); Level 5 (n = 8). Thirty-eight (57%) of the treatable IEMs mimicking CP can be identified by ready available metabolic screening tests in blood or urine, while the remaining IEMs require more specific and sometimes invasive tests.ConclusionsLimited by the rare nature of IEMs and incomplete information in the literature, we conclude that (1) A surprisingly large number of IEMs can present with CP symptoms, as ‘CP mimics’, (2) although individually rare, a large proportion of these diseases are treatable such that neurological damage can either be reversed or prevented, (3) clinician awareness of treatable CP mimics is important for appropriate screening, diagnosis, and early intervention, and (4) systematic studies are required to elucidate the collective frequency of treatable IEMs in CP.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0197-2) contains supplementary material, which is available to authorized users.

Losing a diagnosis of cerebral palsy: a comparison of variables at 2 and 5 years

“…This study aims to determine which variables at 2 years are associated with losing a CP diagnosis by 5 years to help practitioners think about the possibility of an alternate diagnosis to CP when infants/children present with a CP phenotype that evolves atypically. It is important to get the ‘right’ diagnosis early on since some children may have conditions that are treatable and/or genetically determined, thus having recurrence risk and familial implications …”

Current therapies and therapeutic decision making for childhood‐onset movement disorders

“…While several disorders mentioned in the above resources are modifiable with specific interventions, we highlight those disorders in Table where a disease‐modifying intervention can cause significant improvement of movement disorders, plateauing of disease course, or complete remission. There are other treatable inborn errors of metabolism that may manifest with movement disorders in adulthood or may present with spastic diplegia or ataxia, which are discussed in comprehensive reviews …”

“…There are other treatable inborn errors of metabolism that may manifest with movement disorders in adulthood or may present with spastic diplegia or ataxia, which are discussed in comprehensive reviews. 11,13…”

GLUT1 Deficiency in a Patient Diagnosed as Cerebral Palsy: Is NGS a Valuable Tool to Be Considered in All Cases of CP to Detect Underlying Genetic Disorders?

“…Given that the definition is wide, a lot of neurodevelopmental disorders can resemble CP clinically, and the diagnostic workup that should be applied before attributing a patient's phenotype to a perinatal injury is not well defined. In a review from 2014, the researchers identified no less than 110 inborn errors of metabolism that could mimic CP . This is a very important subject matter, given that some of them are treatable (67 of 110 in the review).…”

“…In a review from 2014, the researchers identified no less than 110 inborn errors of metabolism that could mimic CP. 4 This is a very important subject matter, given that some of them are treatable (67 of 110 in the review). Because the age of onset is by definition in infancy or childhood, diagnosis is usually made by pediatricians.…”