Revising the Psychiatric Phenotype of Homocystinuria.

PURPOSE: Associations of psychiatric and psychological symptoms with homocystinuria (HCU) have been described in multiple reports. This retrospective study was undertaken to refine the psychological phenotype among HCU patients and identify biomedical markers that could be used for prediction of those psychiatric or psychological symptoms. METHODS: This study examines the prevalence of psychological symptoms within a sample of 25 patients with classical homocystinuria. RESULTS: Psychological symptoms were noted in 16 of the 25 patients in the sample (64%), including a high prevalence of both anxiety (32%) and depression (32%) and correlated with IQ < 85. There was no difference in the type or the number of psychological symptoms between those diagnosed from newborn screening and early treated and those treated after 2 years of age. CONCLUSION: The results support the possible role of homocysteine as a risk factor for psychological and psychiatric problems and cognitive deficits and suggest that earlier diagnosis and treatment may reduce risk of their occurrences. Although early treatment clearly prevented serious medical complications, psychological and psychiatric symptoms were not associated with medical complications, highlighting the need for continued investigation.

Increased susceptibility to mild neonatal stress in MTHFR deficient mice.

Early life stress is shown to have a life-span outcome on human and animal behavior, increasing the risk for psychopathology. The gene methylenetetrahydrofolate reductase (MTHFR), which encodes for a key enzyme in one carbon metabolism, shows a high prevalence of polymorphism in patients with developmental disorders. Here we examined the hypothesis that MTHFR deficiency results in an increased susceptibility of the developing brain to mild neonatal stress (NS). Mild NS failed to alter corticosterone levels in young and adult Wt mice. However, an elevated level of corticosterone was found in the MTHFR deficient-NS female, exemplifying enhanced sensitivity to NS. Behavioral phenotyping of Wt and MTHFR deficient mice provides evidence that the effect of mild NS may be amplified by the MTHFR deficient genotype. Distinct behavioral characteristics were altered in male and female mice. In general, three patterns of influence on mice behavior were observed: (1) an additive suppressive effect of NS and MTHFR deficiency on exploration and activity was evident in females; (2) stress related parameters were significantly sensitive to genotype in females, presenting an interaction between genotype and sex; (3) various aspects of behavior in a social setting were modified preferably in males by genotype, NS and the interaction between the two, while females exhibited a smaller effect that was restricted to NS with no genotype effect. Overall, our results support an interaction between mild NS, the MTHFR genotype and sex. We suggest using this animal model to study the molecular mechanism linking these two risk factors and their involvement in neurodevelopmental disorders such as schizophrenia and autism.

Assessment of visual function in children with methylmalonic aciduria and homocystinuria.

The aim of this study was to assess various aspects of visual function in 6 patients (age range: 9 months to 7 years and 8 months) with methylmalonic aciduria and homocystinuria. All patients had an ophthalmological examination and were tested with a battery of age-appropriate tests assessing various aspects of visual function such as acuity, visual fields and visual attention. None of the patients had significant retinal abnormalities but all 6 had nystagmus which was associated with strabismus in 3 of the 6. They all had some abnormalities on the behavioral tests assessing visual function which appeared to be related to the age of the patients. Visual impairment was more severe in the 3 patients below 3 years of age and milder in the older patients. The presence and the severity of abnormalities, in contrast, did not depend on the age at onset or the age when treatment was started and were only partly related to brain MRI findings. Severe hydrocephalus and basal ganglia involvement were associated with severe visual impairment, but abnormal visual findings were also present in the children with normal MRI and isolated mild periventricular changes. Our results suggest that age, brain lesions and other factors may be responsible for visual abnormalities in methylmalonic aciduria and homocystinuria. Further studies using early and sequential assessment of visual function are needed to establish whether the differences observed between younger and older children may be related to the duration of therapy.

Social outcome in treated individuals with inherited metabolic disorders: UK study.

Few data exist on the long-term social outcome of patients with inherited metabolic disorders, despite the fact that increasing numbers are surviving into adulthood. Here we report the findings of 329 patients aged from 11 to 70 years, of whom 172 had phenylketonuria, 38 had homocystinuria and 33 had galactosaemia. Twenty-eight per cent had no formal education qualifications, 59% were employed, but only 17% were in professional jobs (social classes I and II). The time of diagnosis and treatment had a significant impact on outcome in phenylketonuria, as did pyridoxine responsiveness or lack of it in homocystinuria. Effects on outcome in galactosaemia were not clear. Social integration is an important outcome of treatment of chronic disorders in childhood and warrants further study in this growing patient population.

Monitored anesthesia care is not synonymous with low risk.

Monitored anesthesia care can lead operating room (OR) personnel, both perioperative nurses and anesthesia providers, into a sense of complacency. It is not general anesthesia, so there is no stress surrounding intubation and extubation and the patient is in control of his/her own respirations. When used properly, narcotics and sedative drugs sedate and relieve pain, but should not lead to respiratory compromise. As a result, circumstances should be under control when competent staff are present. However, because unanticipated events do happen even under the most benign-appearing occurrences, there must be a sense of vigilance by everyone in the OR as this case study relates.

Homocystinuria and schizophrenia. Literature review and case report.

The autosomal recessive disorder homocystinuria involves, in all its subgroups, an abnormality of methionine metabolism. The metabolism of methionine has been a central focus of interest for those who propose the transmethylation hypothesis of schizophrenia. The "methionine effect," as described in the research literature, is thus a theoretical link between these two disorders. The authors review the literature and describe those cases where both have occurred in the same patient. They indicate that whereas many patients with homocystinuria have been psychotic, few have been actually labeled schizophrenic. A patient with homocystinuria, mental retardation, and episodic psychosis is described and this case is used to point to the difficulties in making a definite psychiatric diagnosis in these patients. A relationship between the two syndromes is suggested.