Introduction
Method
Type of psychiatric disorder | Number of titles found | Number of abstracts viewed | Numbers of articles included for review |
---|---|---|---|
ADHD | 316 | 34 | 10 |
Autism | 559 | 101 | 19 |
Eating disorders | 1513 | 18 | 5 |
Learning disorders | 726 | 49 | 17 |
Psychosis | 1327 | 47 | 20 |
Total (including review) | 4441 | 249 | 71 |
Literature search
Autism spectrum disorders
Associated signs and symptoms | Possible underlying metabolic disease | Other signs and symptoms of the metabolic disease | Onset of the metabolic disease |
---|---|---|---|
Mental retardation and behavioural problems (such as aggressive behaviour, hyperactivity, impulsivity, agitation) | Untreated PKU Disorders in purines metabolism Lesh–Nyhan Succinic semialdehyde dehydrogenase deficiency Smith–Lemli–Opitz syndrome Mucopolysaccharidosis type II (Hunter) X-linked ichthyosis | Seizures, eczema Seizures, spastic paraplegia, self-mutilation Seizures, hypotonia, ataxia, intermittent lethargy, speech delay Feeding difficulties in infancy, muscle hypotonia, facial dysmorphism, expressive language disorders, excessive screaming in early childhood, genital abnormalities in the male Retinitis pigmentosa, chronic diarrhoea, regression, sleep problems Scaly skin on the scalp, trunk and limbs (ichthyosis) | Neonatal First years After 3 months After infancy During first year From birth |
Regression | Cerebral folate deficiency Mucopolysaccharidosis type II (Hunter) | Deceleration of head growth, psychomotor retardation, cerebellar ataxia, dyskinesias, seizures, apnea, megaloblastic anaemia Cfr supra | 1 -12 months Cfr supra |
Seizures or epilepsy | Untreated PKU Disorders in purines metabolism Dihydropyrimidine dehydrogenase deficiency Dihydropyrimidinase Deficiency Cerebral Creatine deficiency Biotinidase deficiency Biotinidase or Late-onset carboxylase deficiency Succinic semialdehyde dehydrogenase deficiency Late infantile ceroid lipofuscinosis Urea cycle disorders Hyperammonaemia Acute intermittent porphyria (AIP) L-2-hydroxyglutaric aciduria Mitochondrial disorders OXPHOS defects | Cfr supra Cfr supra Psychomotor retardation, growth retardation, failure to thrive, microcephaly, ocular abnormalities, self-mutilation, muscle weakness, haemolytic anaemia, asymptomatic patients Extrapyramidal signs, speech delay Ataxia, hypotonia, organic acidemia, alopecia, skin rash, visual and hearing loss Cfr supra Developmental delay, speech acquisition delay, myoclonus, ataxia, choreiform movement, visual loss, dementia Hepatomegaly, abnormal hair, hepatic fibrosis, intellectual and developmental disabilities, learning disabilities, confusion, delusion, tone change, reflex abnormalities, vomiting, headache, changing food habits Anxiety, restlessness, insomnia, psychosis, aggressive and impulsive behaviour, catatonia, intestinal problems, dark urine, skin lesions, acute peripheral neuropathy (paralysis of diaphragm) acroparesthesia Developmental retardation, macrocephaly, cerebellar ataxia Central nervous system dysfunction, behavioural disturbance, cognitive impairment, motor disturbances, muscle hypotonia and exercise intolerance | Cfr supra Cfr supra During first year 3 months –2 year 1–12 months Cfr supra After 2 years From birth OTC is a X-linked disorder with episodic clinical presentation in females Adolescence to adulthood Especially in women Childhood From infancy to adulthood |
Speech or language impairment | Cerebral Creatine deficiency Smith–Lemli–Opitz syndrome Late infantile ceroid lipofuscinosis Histidinemia Propionic acidemia | Cfr supra Cfr supra Cfr supra Mental retardation, asymptomatic patients Behavioural problems, hyperammonaemia, metabolic acidosis | Cfr supra Cfr supra Cfr supra Infancy to childhood Neonatal and infancy |
Attention deficit hyperactivity disorder
Associated symptoms and signs | Possible underlying metabolic disease | Other symptoms and signs of the metabolic disease | Onset of the metabolic disease |
---|---|---|---|
Autism and mental retardation | Untreated PKU Succinic semialdehyde dehydrogenase deficiency X-linked ichthyosis Mitochondrial disorders | Mental retardation, seizures Hypotonia, speech delay, seizures, ataxia, psychomotor retardation, intermittent lethargy Scaly skin on the scalp, trunk and limbs (ichthyosis), mental retardation Central nervous system dysfunction, behavioural disturbance, cognitive impairment, motor disturbances, seizures, muscle hypotonia and exercise intolerance | Neonatal After 3 months From birth From infancy to adulthood |
Speech delay | Succinic semialdehyde dehydrogenase deficiency Succinyl-CoA: 3 oxo acid CoA transferase (SCOT) deficiency Mucopolysaccharidosis Type III (Sanfilippo syndrome) | Cfr supra Ketoacidotic crises, persistent ketosis, lethargy, coma, speech and behavioural problems, sleep disorders, anxiety, hallucinations, aggressive behaviour, seizures Developmental or speech delay after a period of normal development, behaviour problems, hyperactivity, mild facial dysmorphism, frequent ear and respiratory infections, chronic diarrhoea | Cfr supra Infancy to adulthood Childhood |
Hypotonia | Succinic semialdehyde dehydrogenase deficiency Nonketotic hyperglycaemia 3-methylcrotonyl-CoA carboxylase deficiency | Cfr supra History of infantile hypotonia and feeding difficulties, mental retardation, ADHD, outburst of aggressiveness, sexual impulsivity Neurological abnormalities and death in infancy, feeding difficulties, recurrent episodes of vomiting and diarrhoea, lethargy, secondary carnitine deficiency, asymptomatic patients | Cfr supra Infancy to adulthood Infancy to adulthood |
Learning disorders
Associated signs and symptoms | Possible underlying metabolic disease | Other symptoms and signs of the metabolic disease | Onset of the metabolic disease |
---|---|---|---|
Neurodegeneration | Adrenoleukodystrophy (X-linked) Metachromatic leukodystrophy Glutaric aciduria type 1 Mucopolysaccharidosis Type III (Sanfilippo syndrome) | Variable phenotype, deterioration in school performance, dementia, vision loss, sensorineural hearing loss, brain white matter abnormalities on MRI, adrenal insufficiency Progressive neurodegeneration. Nonverbal learning disability syndrome, spasticity, brain white matter abnormalities, peripheral neuropathy Acute regression after an initial phase of (almost) normal development (acute encephalopathic crisis), severe dystonic-dyskinetic movement disorder, macrocephaly, MRI of the brain: fronto-temporal atrophy Developmental or speech delay after a period of normal development, behaviour problems, hyperactivity, mild facial dimorphism, frequent ear and respiratory infections, chronic diarrhoea | Childhood to adulthood Infancy to adulthood 6 months to 2 years Childhood |
Seizures | Untreated PKU Glucose transporter type 1 deficiency Hyperinsulinism-Hyperammonaemia syndrome Urea cycle disorders Juvenile neuronal ceroid lipofuscinosis | Autism, ADHD, mental retardation, executive impairment Delayed development in infancy with acquired microcephaly (cerebral/cerebellar atrophy), ataxia Hypoglycaemia, weakness, shakiness, rapid pulse, confusion Hepatomegaly, abnormal hair, hepatic fibrosis, intellectual and developmental disabilities, learning disabilities, tone change, reflex abnormalities, vomiting Progressive deterioration of cognition, ataxia, spasticity, vision loss, learning delay, regression of acquired skills | Neonatal Neonatal Infancy From birth on Infancy to adulthood |
Vomiting and/or diarrhoea | Galactosemia Urea cycle disorders Mucopolysaccharidosis Type III (Sanfilippo syndrome) | Lethargy, vomiting, diarrhoea, failure to thrive, jaundice, cataract, speech difficulties, learning disorders, tremor, ovarian failure, osteoporosis Cfr supra Cfr supra | Infancy to childhood Cfr supra Cfr supra |
Psychosis
Associated signs and symptoms | Possible underlying metabolic disease | Other symptoms and signs of the metabolic disease | Onset of the metabolic disease |
---|---|---|---|
Seizures | Mitochondrial disorders Acute intermittent porphyria (AIP) Urea cycle disorders Methylenetetrahydrofolate reductase deficiency | Central nervous system dysfunction, behavioural disturbance, cognitive impairment, motor disturbances, autism Anxiety, restlessness, insomnia, neuropathy, psychosis, aggressive and impulsive behaviour, catatonia, intestinal problems, dark urine, skin lesions, epilepsy, acute peripheral neuropathy Hepatomegaly, abnormal hair, hepatic fibrosis, intellectual and developmental disabilities, learning disabilities, confusion, delusion, seizure disorders, muscle tone change, reflex abnormalities, vomiting, changing food habits, headache Mild or severe depending on the enzyme activity: encephalopathy, gait disturbance, paraparesis, arterial or venous thrombosis and strokes, neurocognitive impairment, feeding problems, spasticity | Infancy to adulthood Adolescence and adulthood Infancy to adulthood Infancy to adulthood |
Mental retardation | Alpha- Beta-mannosidosis Niemann–Pick type C Homocystinuria | Immune deficiency, facial and skeletal abnormalities, hearing impairment, intellectual disability, progressive neurological signs, episodes of confusion and psychosis followed by a period of confusion, somnolence and asthenia Hepatosplenomegaly, cerebellar ataxia, dysarthria, vertical gaze palsy, cognitive difficulties, progressive neurological deterioration, psychotic symptoms, schizophrenia, behavioural disturbances (aggressiveness, self-mutilation, social isolation, laughing), depressive episodes, bipolar disorders, obsessive–compulsive disorders, infantile cholestatic icterus Lens dislocation, Marfan-like appearance, thromboembolic events, schizophrenia or psychotic episodes (rare), behavioural disorders, depression, obsessive–compulsive disorder, disorganized behaviour, delusions, depression, alteration of consciousness, peripheral neuropathy, coma, paraplegia, strokes, thromboembolic events | Infancy From childhood to adolescence Infancy to adulthood |
Depression | Wilson’s disease Fabry’s disease (X-linked) Tay–Sachs/ Sandhoff disease or GM2 gangliosidosis Niemann–Pick type C Homocystinuria | Ophtalmology: Kayser-Fleisher rings mood disorders, behavioural and personality disorders, cognitive impairment, psychotic symptoms, dysarthria, anxiety Neural pain in hands and feet, cornea verticillata, hearing loss, stroke, renal dysfunction, proteinuria, asymmetric cardiac hypertrophy, angiokeratoma Speech and swallowing difficulties, unsteadiness of gait, spasticity, dystonia, cognitive decline, schizophrenia like psychosis, depression, mania, lower motor neuron disease, sensitive polyneuropathy, dysautonomia, spastic fright reaction, ophthalmology: cherry red spot, blindness Cfr supra Cfr supra | Adolescence and adulthood Adolescence and adulthood Infancy to adulthood Cfr supra Cfr supra |
Eating disorders
Possible underlying metabolic disease | Other symptoms and signs of the metabolic disease | Onset of the metabolic disease |
---|---|---|
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) | Severe cachexia, gastrointestinal dysmotility, progressive external ophthalmoplegia, peripheral neuropathy | Infancy to adulthood |
Mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS) | Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes | Infancy to adulthood |
Methylmalonic and propionic aciduria | Developmental delay, cardiomyopathy, renal failure, opticus atrophy | From birth |
Urea cycle disorders | Hepatomegaly, abnormal hair, hepatic fibrosis, intellectual and developmental disabilities, learning disabilities, confusion, delusion, seizure disorders, muscle tone change, reflex abnormalities, vomiting, headache, changing food habits | Infancy to adulthood |
Conclusions
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A positive family history of metabolic disease.
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Symptoms or signs are triggered by food intake (esp high protein content foods), fever, fasting, surgery (catabolism).
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Feeding difficulties, food refusal, failure to thrive, eating disorders combined with symptoms of myopathy or fatigue.
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Mental retardation and/or regression.
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Epilepsy, episodes of lethargy or confusion.
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Dysmorphic feature.