Psychomotor retardation

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency has been recorded in only a few patients and these show wide variation in clinical presentation. The defect has been seen in infants with a syndrome of psychomotor retardation and failure to thrive. These infants showed abnormal organic aciduria, and drastically decreased SCAD activity was demonstrable in cultured fibroblasts. Muscle symptoms were only part of a wider syndrome in all infants and children so far reported to have SCAD deficiency, but were the sole presenting feature in two adult patients, in whom lipid storage was demonstrable in skeletal muscle. The gene encoding for human SCAD has been mapped to chromosome 12. 

This complex consists of four subunits, all of which are encoded on nuclear DNA, synthesized on cytosolic ribosomes, and transported into mitochondria. The succinate dehydrogenase (SDH) component of the complex oxidizes succinate to fumarate with transfer of electrons via its prosthetic group, FAD, to ubiquinone. It is unique in that it participates both in the respiratory chain and in the tricarboxylic acid (TC A) cycle. Defects of complex II are rare and only about 10 cases have been reported to date. Clinical syndromes include myopathy, but the major presenting features are often encephalopathy, with seizures and psychomotor retardation. Succinate oxidation is severely impaired (Figure 11). 

Generally affect the central nervous system, resulting in psychomotor retardation and other features... 

As indicated above, Man 6-P serves as a chemical marker to target certain lysosomal enzymes to that organelle. Analysis of cultured fibroblasts derived from patients with I-cell (inclusion cell) disease played a large part in revealing the above role of Man 6-P. I-cell disease is an uncommon condition characterized by severe progressive psychomotor retardation and a variety of physical signs, with death often occurring in the first decade. Cultured cells from patients with I-cell disease were found to lack almost all of the normal lysosomal enzymes the lysosomes thus accumulate many different... 

Depression occurring as part of bipolar disorder may be severe and accompanied by ideas of guilt and hopelessness, an inability to function at work because of poor concentration and psychomotor retardation or agitation, poor judgement and suicidal ideation. The lifelong risk of suicide in people with this condition is as high as 15%. Factors associated with suicide risk include alcohol misuse, marital separation or divorce, living alone and unemployment, and these are all common secondary consequences of the illness. 

This behavioural syndrome, rather emotively called learned helplessness", is widely believed to share many features of depression, not least because both culminate in psychomotor retardation and both are linked with experience of uncontrollable, unpredictable stress. Whether or not learned helplessness really is an analogue of depression remains controversial (Maier 1993). Nevertheless, escape deficits in rats are prevented by pretreatment with antidepressants from different generic groups. Other psychotropic agents, such as CNS stimulants and neuroleptics, are generally ineffective. 

Although some studies show that noradrenaline inhibits neuronal firing it is generally considered to increase behavioural activity and arousal. This impression is borne out to the extent that CNS stimulants, like amphetamine, increase release of noradrenaline and produce behavioural and EEG arousal, while reserpine, which reduces noradrenaline storage and hence release, causes psychomotor retardation. It is also supported by... 

Euphoria and sedation are the most prominent effects analgesia is also prominent slurred speech, and impaired memory and attention can be seen along with psychomotor retardation... 

Agitation or slowing Psychomotor retardation (an actual physical slowing of speech, movement and thinking) or psychomotor agitation (observable pacing and physical restlessness) often are present in severe major depressive disorder. 

Other causes of PKU secondary to defective tetrahydrobiopterin synthesis include GTP cyclohydrolase deficiency and 6-pyravoyltetrahydrobiopterin synthase deficiency. Patients with either defect have psychomotor retardation, truncal hypotonia with limb hypertonia, seizures and a tendency to hyperthermia. The intravenous administration of BH4 may lower blood phenylalanine levels but this cofactor may not readily cross the blood-brain barrier. Treatment with synthetic pterin analogs or supplementation with tryptophan and carbidopa may prove more efficacious, particularly if treatment is started early in life. 

Intrauterine seizures may occur. The electroencephalogram often displays a hypsarrhythmia or a burst-suppression pattern. Patients display myoclonic jerks, hiccuping and a profound hypotonia. The few patients who survive past the first week usually sustain profound mental retardation and neurological disability. Brain imaging shows atrophy and a loss of myelin. Rarely, patients present later in life with psychomotor retardation and growth failure. Others have had initial normal development followed by a progressive loss of developmental milestones. Some patients have manifested spinocerebellar degeneration and other symptoms of motor dysfunction [27],... 

About half of individuals who do not respond to pyridoxine will sustain ectopia lentisbj age 5-10 years. Indeed, the diagnosis commonly is made by an ophthalmologist. The median IQ score for B6 responsive and nonresponsive patients is 78 and 56 respectively. Some children present at 1-2 years with psychomotor retardation, convulsions (=20% of cases) and psychiatric difficulties such as depression and personality disorders (=50% of cases). 

Diagnosis of a urea cycle defect in the older child can be elusive. Patients may present with psychomotor retardation, growth failure, vomiting, behavioral abnormalities, perceptual difficulties, recurrent cerebellar ataxia and headache. It is therefore essential to monitor the blood ammonia in any patient with unexplained neurological symptoms, but hyperammonemia is inconstant with partial enzymatic defects. Measurement of blood amino acids and urinary orotic acid is indicated. 

Multiple sulfatase deficiency (MSD). The clinical presentation of MSD includes features of MLD and the MPS, with the features that resemble MLD, such as gait disturbances, psychomotor retardation and polyneuropathy predominating. MPS-like features, such as facial coarsening, hepatosplenomegaly and joint stiffness, are present to a milder and variable extent. A reduction in the activity of all sulfatases is the key diagnostic abnormality. Von Figura and associates have demonstrated that catalytic activity of all sulfatases requires a post-translational modification in which a cysteine residue (cysteine 69 in arylsulfatase A) is oxidized to an aldehyde. It is this modification that is defective in MSD [5]. 

In bipolar depression, patients often have mood lability, hypersomnia, low energy, psychomotor retardation, cognitive impairments, anhedo-nia, decreased sexual activity, slowed speech, carbohydrate craving, and weight gain. 

Psychomotor disturbances may include psychomotor retardation (slowed physical movements, thought processes, and speech) or psychomotor agitation. 

D. The symptoms are not better accounted for by bereavement (i.e., after the loss of a loved one), the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. 

Tay-Sachs Hexosaminidase A Ganglioside GMj Cherry red spots in macula Blindness Psychomotor retardation Death usually <2 years... 

Depressed mood is the hallmark symptom of MDD, but it is neither required nor sufficient for the diagnosis of major depression. In addition to depressed mood, the key symptoms of a major depressive episode include anhedonia, changes in sleep or appetite, psychomotor retardation or agitation, poor concentration or indecisiveness, and recurrent thoughts of death or suicide. The DSM-IV definition of major depression requires that five or more of these symptoms be present for at least 2 weeks in the absence of an identifiable cause such as medication, medical illness, or the death of a loved one. Refer to Table 3.2 for the DSM-IV criteria for MDD. 

Antidepressants. There are numerous reasons to expect that antidepressants may be helpful in the treatment of AN. First, depressed mood and other symptoms of depression such as anhedonia, decreased energy, poor concentration, and psychomotor retardation are common in cases of starvation from any cause. Second, AN patients and their family members have high rates of comorbid MDD and OCD, illnesses best treated with antidepressant medications. Finally, weight gain is a well-documented side effect of many antidepressants including the tricyclic antidepressants (TCAs) and mirtazapine. 

Symptoms of PDH deficiency include weakness, ataxia, and psychomotor retardation due to damage to the brain, which is the organ most reliant on the TCA cycle to supply its energy needs. 

Patients with l-cell disease exhibit severe psychomotor retardation coarse facial features and skeletal malformations, including kyphoscoliosis, anterior beaking of the vertebrae, and a lumbar gibbus deformity. 

Acute administration of opioids, particularly in non-tolerant individuals, produces a syndrome of intoxication characterized by pupillary dilation and initial euphoria, followed by apathy, psychomotor retardation, slurred speech, and impaired attention and memory. Opioid overdose can produce fatal respiratory depression and thus is a medical emergency. 

Many of the children and adolescents seen for treatment of depression are experiencing their first depressive episode. Because the symptoms of unipolar and bipolar depression are similar, it is difficult to decide whether a patient needs only an antidepressant or concomitant use of mood stabilizers. As noted above, symptoms and signs such as psychosis, psychomotor retardation, or family history of bipolar disorder may warn the clinician about the risk of the child developing a manic episode. 

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