Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3.

BACKGROUND: Hereditary hypophosphatemia is a group of rare renal phosphate wasting disorders. The diagnosis is based on clinical, radiological, and biochemical features, and may require genetic testing to be confirmed. METHODOLOGY: Clinical features and mutation spectrum were investigated in patients with hereditary hypophosphatemia. Genomic DNA of 23 patients from 15 unrelated families were screened sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1. CytoScan HD Array was used to identify large deletions. RESULTS: Genetic evaluation resulted in the identification of an additional asymptomatic but intermittent hypophosphatemic subject. Mutations were detected in 21 patients and an asymptomatic sibling from 13 families (86.6%, 13/15). PHEX mutations were identified in 20 patients from 12 families. Six of them were novel mutations present in 9 patients: c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887-22,395,767del (179880 bp deletion including exon 16-22 and ZNF645). Six previously reported mutations were found in 11 patients. Among 12 different PHEX mutations, 6 were de novo mutations. Patients with de novo PHEX mutations often had delayed diagnosis and significantly shorter in height than those who had inherited PHEX mutations. Novel compound heterozygous mutations in SLC34A3 were found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14. No mutation was detected in two families. CONCLUSIONS: This is the largest familial study on Turkish patients with hereditary hypophosphatemia. PHEX mutations, including various novel and de novo variants, are the most common genetic defect. More attention should be paid to hypophosphatemia by clinicians since some cases remain undiagnosed both during childhood and adulthood.

Role of plasma homocysteine and lipoprotein (a) in coronary artery disease.

This study looks at the possible role of some non-traditional risk factors for premature coronary artery disease (CAD) and assesses the presence of relationship between these factors and the traditional cardiovascular risk factors. The study subjects (n=45) are divided into three groups comprising 15 premature CAD patients without traditional cardiovascular risk factors (group I); 15 premature CAD patients with one or more traditional cardiovascular risk factors (group II); and 15 healthy normal control subjects matched for age and sex (group III). Estimation of plasma homocysteine (Hcy) and plasminogen activator inhibitor-1 (PAI-1) is performed by enzyme-linked immunosorbent assay (ELISA); plasma folic acid by radioimmunoassay; plasma lipoprotein a (Lpa) by turbidimetry; and plasma lipids by colorimetry. Results showed a significant association between elevated Hcy and low folate levels and premature CAD in both patient groups. Also, a significant association was seen between elevated PAI-1 and CAD in the two patient groups, and between CAD and high levels of Hcy and triglycerides, as well as a low level of high-density lipoprotein cholesterol. Lpa showed significant association with premature CAD only in group II. Thus, Hcy, folic acid and PAI-1 might serve as independent risk factors for premature CAD in patients both with and without traditional coronary risk factors. However, Lpa might confer an additional coronary risk factor only in the presence of traditional risk factors.

Cerebral blood flow in alcohol withdrawal: relation to severity of dependence and cognitive impairment.

BACKGROUND: Alcohol dependence affects cerebral function in complex, still unsettled ways. METHODS: Thirty exclusively alcohol-dependent patients in various stages of withdrawal and 25 matched controls were examined for regional uptake of 99mTc-HMPAO in nine homologous regions of the cerebral cortex by single photon emission tomography (SPET). Image analysis reports regional uptake/uptake in homologous hemisphere. RESULTS: Alcohol dependence is associated with diminished perfusion in the anterior, and middle frontal regions, and increased perfusion in the posterior temporal regions. Frontal hypoperfusion is related to alcohol withdrawal because it disappears with longer time between imaging, last intake and correlates with a composite index of cognitive impairment at the time. Temporal hyperperfusion persists for longer periods. Severe dependence correlates with both frontal, and temporal altered perfusion. DISCUSSION: Alcohol withdrawal leads to redistribution of blood flow favouring the temporal, and more posterior regions of the cortex at the expense of frontal flow.

Single photon emission tomography with 99m Tc-HMPAO in Arab patients with depression.

BACKGROUND: This study investigates the rate of cerebral blood flow (rCBF) in Arab patients wth depression. METHODS: Forty-four patients with DSM-III-R major depressive disorders were studied at rest using single photon emission computerized tomography (SPECT) with 99m Tc-HMPAO in comparison with 20 normal controls. All patients were assessed using the Hamilton Rating Scale for Depression (HRSD). RESULTS: The depressed group showed greater rCBF in left and right posterior frontal and parietal cortical regions than normal controls. Within the depressed group, patients with the least severe illness (HRSD < 20) had significantly lower rCBF than normal controls, whilst those with moderately severe (HRSD 20-29) and severe (HRSD > 30) had significantly greater rCBF in most cortical regions than normal controls. Symptom scores, derived from the HRSD were predicted by rCBF principally increased rCBF in the left frontal cortex. CONCLUSIONS: These results suggest a generalized cerebral activation principally in the frontal cortex which is in contrast to the results of most previous studies but more in line with the results of studies of induced affect and some studies of depression subsyndromes.

The Dubai Community Psychiatric Survey. IV. Life events, chronic difficulties and psychiatric morbidity.

The relationship between life events, chronic social difficulties and psychiatric morbidity was investigated in 297 women selected at random as part of the Dubai Community Psychiatric Survey. The PSE-ID-CATEGO system was used to identify psychiatric cases, based on an Index of Definition level of 5 or more. Life events in the 6-month period prior to illness or interview were elicited through the Life Events and Difficulties Schedule. Chronic difficulties were explored through direct questioning based on a list of possible problems. The study demonstrates a significant excess of marked and moderately threatening life events in acute cases of psychiatric disorder (50%) compared to chronic cases (16.7%) and non-cases (27.9%). The association was particularly marked for events in the 3-month period before the onset. Around 33% of psychiatric morbidity may be attributed to marked and moderately threatening life events. Rates for mild events were similar in the three groups of subjects. Subjects experiencing chronic social difficulties included a significantly higher proportion of cases (33.3%) than those who did not experience such difficulties (9.1%). The effect of chronic social difficulties was more pronounced than, and independent of, the effects of life events. There were no interactions between life events and vulnerability factors in their effect on psychiatric morbidity, although numbers were small. The results suggest that the overall influence of life events and chronic difficulties on psychiatric morbidity is commensurate with that in Western societies, despite the different coping traditions of Islam.

Problems in validating endogenous depression in the Arab culture by contemporary diagnostic criteria.

This study highlights the difficulties that may be encountered in attempting to apply the clinical construct of endogenous depression derived from western studies to depressed Arab patients. The agreement between 4 operational systems on the diagnosis of endogenous (melancholic) depression is explored in 100 patients with primary depressive disorder in Al-Ain, United Arab Emirates. The symptom characteristics of the 61 patients in whom all diagnostic systems agreed are then described quantitatively and qualitatively. Subjects were evaluated by the Newcastle scale, Hamilton's 21 item depression scale, global assessment of functioning scale, and the operational criteria of the diagnostic systems used. Diagnosis of endogenicity was derived by computer according to the respective criteria. The agreement between DSM-IV, ICD-10, and RDC criteria is moderately high (0.72). When the Newcastle Index is included, it is only moderate (0.58). Disagreements are related to differences in diagnostic criteria. Small differences affect concordance appreciably. DSM-IV agreed with a majority of external validators, differentiating a more homogeneous groups of patients. In the present study, endogenous depression identified by western criteria, was less likely to manifest by guilt feelings, a distinct quality of mood, and loss of libido. The descriptions of patients reveal that the mood component of depression is expressed differently, somatic metaphors are used frequently to express distress, religious elements influence the expression of symptoms, and depression may manifest in behaviours not directly indicative of the disorder. Endogenous depression may be identified in the Arab culture, but considerable variation in its component symptom frequencies and mode of expression needs to be taken in consideration for defining it in terms appropriate to the culture.

Mass hysteria in an Arab culture.

In this report we describe the circumstances surrounding an outbreak of mass hysteria among first year female university students. The outbreak was precipitated by a state of panic over the possibility of a fire which turned out to be harmless fumes from a locally used burning perfume. Twenty-three cases presented to the emergency room with symptoms of respiratory distress associated with marked emotional reactions. The outbreak was controlled by separating the patients, and the lack of media coverage facilitated this process. Cases with persistent and severe symptoms were those having physical and psychological problems prior to the occurrence of the outbreak. Individual vulnerability factors deserve special consideration in the management of mass hysteria since they are likely to influence the response to treatment.

Performance of the Hamilton Depression Rating Scale in depressed patients in the United Arab Emirates.

Cross-cultural variation in the frequencies and modes of expression of depressive symptoms may influence the validity of depression rating scales. The most widely used instrument for this purpose, namely Hamilton's Depression Rating Scale (HDRS), has not been systematically evaluated in Arab countries. This study evaluates the face validity of the HDRS-21 by studying symptom frequencies, factor structure and symptom clusters in 100 UAE depressed patients. Concurrent validity is tested by comparing total HDRS scores with global estimates of severity made by clinicians, admission status, impairment of social and occupational functioning, and the endogenicity score of the Newcastle (NC) Diagnostic Index. Total HDRS scores show highly significant agreement with three independent measures of severity of depression. Rank orders of the most and least frequent symptoms are consistent with studies of similar design. Marked differences lie in more retardation and somatization and fewer cognitive components in the present study. Principal-component analysis confirmed the heterogeneous structure of the scale, separating a group of core depressive symptoms, and endogenous, somatization, anxiety and psychotic symptom components. The internal consistency (reliability) of the whole scale is moderate, and improves in the core symptom factor. The main conclusion is that the HDRS is sensitive to severity of depression in the UAE culture. However, it measures heterogeneous aspects, and its internal consistency suffers as a result. High levels of retardation and somatization contribute significantly to the total score in socially developing communities.

The Dubai Community Psychiatric Survey: acculturation and the prevalence of psychiatric disorder.

Dubai, an Emirate in the Gulf region, has experienced spectacular social change as a result of the exploitation of its oil reserves. The Dubai Community Psychiatric Survey was designed to study the effects of this social change on the mental health of female nationals. In this paper, we approach the problem by quantifying social change in two main ways: the first focused on social change at the individual level as measured by the Socio-cultural Change Questionnaire (Bebbington et al. 1993). The second examined the effect of social change at the community level by identifying areas of residence at different levels of development. We hypothesized that attitudes and behaviours markedly at odds with traditional prescriptions would be associated with high rates of psychiatric morbidity. On the individual level, the association between psychiatric morbidity and the amount of social change reflected in the behaviours and views of the subjects was not significant. However, there was a significant association between morbidity and between social attitudes and behaviours. At the community level, in contrast, the relationship between psychiatric morbidity and social change was significant: there was more psychiatric morbidity in areas at the extremes of the social change continuum. The hypothesis put forward in this study must be modified accordingly.

The Dubai Community Psychiatric Survey: II. Development of the Socio-cultural Change Questionnaire.

The Dubai Community Psychiatric Survey was carried out to assess the effect of very rapid social change on the mental health of women in Dubai, one of the United Arab Emirates. In order to measure social change at an individual level, we developed a questionnaire covering behaviour and attitudes in a wide range of situations, the Socio-cultural Change Questionnaire (ScCQ). In this paper we give an account of the considerations that determined the form of the ScCQ, its structural characteristics, and its validity.

The Dubai Community Psychiatric Survey: I. Prevalence and socio-demographic correlates.

This paper describes the methods and initial sociodemographic findings of the first community psychiatric survey from an Arabian country. It was carried out on a sample of women in Dubai, one of the seven United Arab Emirates. Psychiatric status was established using the PSE-ID-CATEGO system. The overall prevalence of disorder in these women was a high 22.7% (13.7% depressive disorders; 7% anxiety states). There was little association with sociodemographic variables, except that prevalence was high in divorced, widowed and separated women, polygamously married women and single parents. The high prevalence may be related to the rapid sociocultural change in this society. Future reports will examine the influence of sociocultural change at an individual level.

Clinical correlates of intent in attempted suicide.

The seriousness of suicide attempts was evaluated in 62 consecutive referrals in 2 general hospitals. As measured by the Suicide Intent Scale (SIS) the majority of cases had a low to moderate intention to die. Increasing age, psychosis and deliberate self-injury were associated with high suicidal intent. Hopelessness and a sense of isolation are significantly more frequent antecedent ideo-affective states in cases with high intent and anger and frustration are more prevalent in cases with low intent. Two other measures of seriousness, the medical condition on admission and lethality of the method used, correlate significantly with the degree of intent. The SIS can distinguish between relatively homogeneous subgroups of suicide attempters for depth studies of aetiology and management.