What percentage of all cases of intellectual disabilities have a known organic cause?
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AbstractBackgroundIntellectual disability (‘developmental delay’ at age < 5 years) affects 2.5% of population worldwide. Recommendations to investigate genetic causes of intellectual disability are based on frequencies of single conditions and on the yield of diagnostic methods, rather than availability of causal therapy. Inborn errors of metabolism constitute a subgroup of rare genetic conditions for which an increasing number of treatments has become available. To identify all currently treatable inborn errors of metabolism presenting with predominantly intellectual disability, we performed a systematic literature review. MethodsWe applied Cochrane Collaboration guidelines in formulation of PICO and definitions, and searched in Pubmed (1960–2011) and relevant (online) textbooks to identify ‘all inborn errors of metabolism presenting with intellectual disability as major feature’. We assessed levels of evidence of treatments and characterised the effect of treatments on IQ/development and related outcomes. ResultsWe identified a total of 81 ‘treatable inborn errors of metabolism’ presenting with intellectual disability as a major feature, including disorders of amino acids (n = 12), cholesterol and bile acid (n = 2), creatine (n = 3), fatty aldehydes (n = 1); glucose homeostasis and transport (n = 2); hyperhomocysteinemia (n = 7); lysosomes (n = 12), metals (n = 3), mitochondria (n = 2), neurotransmission (n = 7); organic acids (n = 19), peroxisomes (n = 1), pyrimidines (n = 2), urea cycle (n = 7), and vitamins/co-factors (n = 8). 62% (n = 50) of all disorders are identified by metabolic screening tests in blood (plasma amino acids, homocysteine) and urine (creatine metabolites, glycosaminoglycans, oligosaccharides, organic acids, pyrimidines). For the remaining disorders (n = 31) a ‘single test per single disease’ approach including primary molecular analysis is required. Therapeutic modalities include: sick-day management, diet, co-factor/vitamin supplements, substrate inhibition, stemcell transplant, gene therapy. Therapeutic effects include improvement and/or stabilisation of psychomotor/cognitive development, behaviour/psychiatric disturbances, seizures, neurologic and systemic manifestations. The levels of available evidence for the various treatments range from Level 1b,c (n = 5); Level 2a,b,c (n = 14); Level 4 (n = 45), Level 4–5 (n = 27). In clinical practice more than 60% of treatments with evidence level 4–5 is internationally accepted as ‘standard of care’. ConclusionThis literature review generated the evidence to prioritise treatability in the diagnostic evaluation of intellectual disability. Our results were translated into digital information tools for the clinician (www.treatable-id.org), which are part of a diagnostic protocol, currently implemented for evaluation of effectiveness in our institution. Treatments for these disorders are relatively accessible, affordable and with acceptable side-effects. Evidence for the majority of the therapies is limited however; international collaborations, patient registries, and novel trial methodologies are key in turning the tide for rare diseases such as these. Highlights► Our review identified 81 metabolic diseases causing intellectual disability. ► Diagnosis is established via screening tests and digital tools www.treatable-id.org. ► Therapeutic modalities (n=91) are generally affordable, accessible, and safe. ► Effects include improved primary (cognition / development) and secondary outcomes. ► Evidence is limited, but often therapies are effective and ‘standard of care’. AbbreviationsDD global developmental delay ID(s) intellectual disability (-ies) IEM(s) inborn errors of metabolism(s) KeywordsInborn errors of metabolism Intellectual disability Developmental delay Therapy Evidence Systematic review Cited by (0)Copyright © 2011 Elsevier Inc. What percent of individuals with intellectual disabilities have no known causes?Among children, the cause of intellectual disability is unknown for one-third to one-half of cases. About 5% of cases are inherited from a person's parents.
What percent of people have an intellectual disability?Intellectual disability affects about 1% of the population, and of those about 85% have mild intellectual disability. Males are more likely than females to be diagnosed with intellectual disability.
What is the cause of organic intellectual disabilities?Several hundred causes have been discovered, but in about one-third of the people affected, the cause remains unknown. The three major known causes of intellectual disability are Down syndrome, Fetal Alcohol Spectrum Disorder (FASD) and Fragile X syndrome.
What percentage of intellectual disabilities are caused by hereditary factors?ID affects about 2–3% of the general population [Curry et al., 1997; De Vries et al., 2005]. A varying proportion of ID cases (ranging from 17% to 50%) are attributable to genetic causes [Moeschler and Shevell, 2006; Kaufman et al., 2010].
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