[Short questionnaire for detecting abnormal eating behavior (binge eating). Test results in 320 persons with normal weight and overweight/obesity]. / Kurzfragebogen zur Diagnostik abnormen Essverhaltens (binge eating). Testergebnisse bei 320 Personen mit Normal- und Ubergewicht/Adipositas.

BACKGROUND: Abnormal eating behavior (binge eating) is widespread, yet very often remains undetected in general medical practice because of the secretiveness of the affected person. A screening questionnaire (KFzE, 8 items, range 0-6) was developed to diagnose this specific eating disorder. Questions relating to or implying psychopathological aspects were excluded to avoid any stigmatization. PATIENTS AND METHODS: A partial score (TSc3) was calculated from the ratings of three core symptoms (1. uncontrollable urge to eat; 2. thinking of food; 3. feeling of satiety). In addition, the ratings of five symptoms depicting more nonspecific aspects of eating abnormalities were added to calculate a total score (GSc8). RESULTS: Based on the score values and cut-off points (the latter derived from the frequency distributions of TSc and GSc), patients suffering from bulimia nervosa without overweight or obesity (BN, group I, n = 51, BMI<25 kg/m2) as well as those with binge eating syndrome very often (91%) associated with overweight or obesity (BES, group II, n = 80, BMI>25 kg/m2) were clearly distinguishable from overweight or obese persons without binge eating (group III, n = 70) and healthy female controls (group IV, n = 119). The small differences in the mean scores between patients with BN and those with BES confirm earlier results obtained with other questionnaires. Moreover, results of the BITE questionnaire (Bulimia Investigatory Test Edinburgh), a proven method for diagnosing binge eating from its symptom subscale (30 items), correspond well with the results obtained from the KFzE for both groups of patients. The KFzE shows good psychometric characteristics such as test-retest reliability (0,92) and internal consistency (a= 0,87) DISCUSSION: The described method gives medical practitioners a simple way of screening a large number of patients of normal weight, overweight or obesity who need careful and early evaluation of a previously unrecognized eating disorder. It can be used for ongoing monitoring as well as for following any type of therapeutic approach in persons with binge eating.

[ACE inhibitor-induced angioedema: remarkable new perspectives for intensive care/emergency medicine]. / ACE-Hemmer-induzierte Angioödeme: Beachtenswerte neue Perspektiven für die Intensiv-/Notfallmedizin.

1. Early and late onset of angio-oedema. The report reviews angio-oedema as a rare but potential life threatening adverse effect associated with angiotensin converting enzyme (ACE) inhibitors. This class of drugs, widely used in the treatment of hypertension and congestive heart failure, may often induce mild angio-oedema of the skin (face, lips, cheeks) but may rarely involve tongue, subglottis, pharyngeal and laryngeal tissues. Angio-oedema has been previously reported to occur early after start of treatment, mostly within the first 3-4 weeks. However, according to later reports since 1990, first onset may be delayed for months and even until 7 years of treatment. Analysis of patients exhibiting angio-oedema reported to the National Drug Commission in Germany revealed that the number of patients with late onset of angio-oedema is continually increasing over time. The percentage of patients with delayed onset ranging from after six months up to six years was as follows: 1992: 8.9% (of a total of n = 56), 1996: 28% (of a total of n = 79), and 1998: 54% (of a total of n = 46). Eleven cases of patients of the latter group were classified as life-threatening. 2. Recurrence of Angio-oedema. Furthermore, many patients experienced multiple episodes of angio-oedema because even clinicians in emergency departments are not familiar with the association between angio-oedema and ACE inhibitors. In our series from 1992 until early 1998 17% of 125 patients exhibiting angio-oedema had relapses with a maximum of seven events over a period of three years. 3. Widespread Use of ACE Inhibitors, Tactical Approach to Diagnosing Angio-oedema and Prevention of Relapses. Hence, from a practical point of view, it seems very useful to suggest that nowadays every angio-oedema is caused by ACE inhibitor treatment until it is definitely excluded by a thorough review of all medications. Thirteen ACE inhibitors gained more widespread application worldwide. Unfortunately, a large number of drug combinations (> 93) are meanwhile on the market. Therefore, much effort is needed to improve the knowledge and awareness of this insidious adverse effect by well-documented case reports. Moreover, each case of ACE inhibitor-associated angio-oedema should be immediately brought to the attention of the practitioner/cardiologist to emphasise that this class of antihypertensive agents is contraindicated in the affected person to prevent the occurrence of another potentially life-threatening event.

Renal sodium handling and neurohumoral systems in patients with cirrhosis in sitting posture: effects of spironolactone and water immersion.

Renal sodium handling, neurohumoral systems, and systemic hemodynamics were investigated under baseline conditions in sitting posture in 10 healthy subjects, 11 patients with cirrhosis without, and 10 patients with cirrhosis with ascites. Furthermore, the effects of head-out water immersion, 1-week spironolactone administration, or their combination was assessed in the two groups of patients. Patients without ascites exhibited a significant increase in plasma norepinephrine concentration and a tendency toward an increase in plasma aldosterone concentration. Patients with ascites had a significantly lower mean arterial blood pressure despite significant reduction of urinary sodium excretion and fractional sodium excretion as well as an increase of plasma renin activity, plasma aldosterone, and norepinephrine concentration. In patients with ascites, the increase in renal sodium excretion and fractional sodium excretion following water immersion or spironolactone was clearly augmented by the combination of the two maneuvers. The same pattern was observed in patients without ascites. Our findings (a) underscore the importance of studying hemodynamics, renal function, and neurohumoral systems also in upright posture, (b) suggest a role of sympatico-adrenergic activation and proximal sodium retention in preascitic patients, and (c) are compatible with the vasodilation hypothesis of ascites formation.

Diagnosis and treatment of 17-hydroxylase deficiency.

Leading symptoms of 17-hydroxylase/17,20-lyase deficiency in childhood are hypertension and hypokalemia. We found this enzyme defect in 3 phenotypically female siblings aged 12, 15 and 16 years. Two of the sibs have a 46,XY chromosome pattern, the third is genetically female. Pubertal development did not occur. Both of the 46,XY sibs have male internal and female external genitalia. The 46,XX sister has normal female internal genitalia. At the time of diagnosis, two of the three siblings had hypertension (RR between 190/135 and 160/110 mmHg). Two of the three siblings had low serum potassium and metabolic alkalosis. All three patients had excessively high plasma levels of 11-deoxycorticosterone (DOC) and corticosterone. Aldosterone was also elevated whereas plasma renin activity was suppressed. Plasma cortisol and its 17-hydroxylated precursors were low, as were plasma testosterone, dihydroepiandrosterone sulphate and estradiol, while the gonadotropins LH and FSH were elevated in all three patients. We studied the steroid profiles of these three patients during long term glucocorticoid treatment with dexamethasone, which is now followed for 13 years. Blood pressure and serum potassium became normal. Plasma aldosterone, corticosterone and DOC were clearly lower but not fully normalized. The two genetically male sisters obtained estrogens for induction of female secondary sex characteristics. The third 46,XX sister has normal menstruations during substitution with cyclic estrogen/gestagen therapy. All three patients lack pubic and axillary hair, and reached normal adult heights both for phenotypic sex and for target height. The psychosocial orientation is female in all of them. Apart from rare reports of development of malignant hypertension, prognosis is better than in other enzyme deficiencies causing congenital adrenal hyperplasia since no Addisonian crises occur due to DOC and corticosterone overproduction resulting in apparently normal endogenous glucocorticoid activity.

[Is determination of the "free androgen index" for hormone screening in polycystic ovaries of value?]. / Ist die Bestimmung des "freien Androgenindexes" zum Hormonscreening bei polyzystischen Ovarien sinnvoll?

In 82 females with hyperandrogenism and polycystic ovaries, the sensitivity and diagnostic accuracy of the free-androgen index (FAI) were compared with those of testosterone (T), free testosterone (fT), androstenedione (A), LH and the LH/FSH ratio. Normal ranges for each parameter were derived as 95th percentile in 53 healthy controls of similar age. T, fT, A, FAI, LH and LH/FSH were significantly (p < 0.001) higher in patients than controls. The sensitivity and diagnostic accuracy of the FAI (0.46 and 0.64) were lower than those of T (0.67 and 0.78) and A (0.56 and 0.73) and similar to those of fT and LH/FSH. The overall variance of the FAI was highest among all parameters. The FAI was significantly (p = 0.05) elevated in a subgroup with obesity (n = 34), whereas T and fT did not differ in obese and nonobese subjects with polycystic-ovary syndrome. We cannot recommend the routine measurement of the FAI in the rational laboratory evaluation of female hyperandrogenism for the following reasons. (1) The adequate normal range for the FAI (< 8.7) is substantially higher than previously thought in normal individuals, which has serious consequences for the accuracy of the test. (2) The values of the FAI showed the widest overlap with controls. (3) The significant positive correlation between FAI and fT allows the prediction of the FAI from the measurement of fT, rendering the determination of a second parameter for the free bioactive T unnecessary. (4) The FAI as well as sex-hormone-binding globulin are influenced by body weight, whereas T and fT are markers for hyperandrogenism independent of obesity.

[Angioneurotic edema caused by angiotensin-converting enzyme inhibitors]. / Angioneurotisches Odem durch Angiotensin-Konversionsenzym-Hemmer.

Inhibition of angiotensin converting enzyme (ACE) may cause angioneurotic oedema. In order to define the clinical spectrum of this important adverse effect, we analysed data on 60 patients with angioneurotic oedema notified to the Drug Commission of the German Medical Association, after taking captopril (n = 24), enalapril (n = 25) or lisinopril (n = 11). In 48 cases the oedema affected the face, tongue and pharynx, while swelling of the extremities (n = 4), the trunk (n = 2) or the genitalia (n = 1) was observed less frequently. While oedema appeared most often after 1 to 21 days, it started within an hour in one patient, and only after 6 months of therapy in five patients. After discontinuation of the ACE inhibitor, the angioneurotic oedema resolved within 72 hours; additional therapeutic measures (glucocorticoids, antihistamines, adrenaline, C1 inhibitors) did not shorten the recovery time. In view of the increasing use of ACE inhibitors, the features of this unusual adverse reaction need to be widely recognized, since angioneurotic oedema of the larynx is potentially life-threatening.

Response of gonadotropins to pituitary stimulation with luteinizing hormone releasing hormone is a more specific than sensitive parameter for the polycystic ovary syndrome.

Gonadotropin response to exogenous luteinizing hormone-releasing hormone (LHRH) was studied in two groups of patients with the polycystic ovary syndrome (PCOS). Group I (n = 44) was diagnosed as 'overt PCOS' based on clinical and endocrine abnormalities, and the typical ultrasonic picture of multicystic changes in an increased amount of ovarian stroma. Group II patients (n = 34), with similar clinical and hormonal changes, were classified as 'borderline PCOS' because endosonography of the ovaries was not conclusive. Serum gonadotropins were followed 15, 30, 45 and 60 min after administration of 100 micrograms LHRH intravenously. Plasma LH and the peak ratio of luteinizing hormone to follicle stimulating hormone (LH/FSH peak) after LHRH were significantly higher in Group I and II patients (p less than 0.001) than in controls (n = 11). There was a significant positive correlation between LH (r = 0.73 and 0.68, p less than 0.05) and LH/FSH ratio peaks (r = 0.61 and 0.68, p less than 0.05) after LHRH, and the basal values in each group. However, hyperreactivity of LH and the LH/FSH ratio after LHRH (defined as values exceeding the 95th percentile of control values) was only present in Group I in 38.6 and 56.8%, and in Group II in 47.1 and 73.5% of patients. It is concluded that: exaggerated LH release after LHRH is a typical yet not unique feature of PCOS and its sensitivity is inferior to its specificity; a higher rate for sensitivity is achieved when the LH/FSH ratio after LHRH (instead of LH release alone) is used; and that hyperreactivity of LH after LHRH is neither correlated with the plasma concentrations of total testosterone, free plasma testosterone or androstenedione, nor with the ultrasonic picture of the ovaries as significantly higher (p less than 0.05) LH and LH/FSH ratio peaks were found in borderline PCOS patients. While the heterogeneity of gonadotropin response to LHRH clearly limits its routine diagnostic use, the FSH and LH response is useful in patients with inconsistent clinical and ultrasonic features suggestive of PCOS.

Hepatic efflux and renal extraction of plasma glutathione: marked differences between healthy subjects and the rat.

Hepatic efflux of glutathione accounts for almost 85% of the plasma level in the rat. However, the expected high concentration in the hepatic vein in man has not been demonstrated as yet. Our findings in ten patients without liver dysfunction reveal that substantial translocation of glutathione from the liver to the plasma does not occur. The removal rate of circulating glutathione by the kidney is far lower in man than in the rat (49.5% vs 84.6%). Moreover, the inferior vena cava in man contains more circulating glutathione than the artery, which is not consistent with the results obtained in the rat. Furthermore, the plasma concentration in man is about one tenth of that in the animals. These results clearly indicate that species-specific differences in the overall biosynthesis and metabolism of the tripeptide occur, resulting in marked variations in its plasma concentration.

Increased bioavailability of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after portacaval shunting.

Metabolites of arachidonic acid have been attributed to severe circulatory, metabolic and hormonal alterations in patients with chronic liver disease. In order to study changes of the tissue-specific availability of enzymes of eicosanoid synthesis, we used portacaval-shunted rats, as this model exhibits many clinical and biochemical similarities to patients suffering from cirrhosis of the liver. Microsomal mass and maximal velocity of prostaglandin H synthase, the initial enzyme of prostaglandin synthesis, were markedly and permanently increased after shunting in both hepatic and extrahepatic tissues as compared to those of sham-operated rats. Maximal velocity of thromboxane synthase and prostacyclin synthase, two more peripheral enzymes of the arachidonic acid cascade, were tissue-specifically enhanced, whereas the apparent affinities (Km) remained unchanged. Determination of 5-lipoxygenase activity in tissue preparations disclosed a preferential increase in the liver, lung and renal cortex after portacaval shunting. Furthermore, exposure to endotoxin closely mimicked the shunting-induced changes. These results suggest that after portacaval shunting and possibly in patients with advanced liver disease, profound abnormalities at the level of local enzyme expression might play a pathophysiologically important role in the control of eicosanoid synthesis.

Atrial natriuretic factor and renin-aldosterone in volume regulation of patients with cirrhosis.

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p less than 0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 +/- 1.3 fmoles per ml to 16.5 +/- 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 +/- 0.6 fmoles per ml to 13.6 +/- 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 +/- 1.3 fmoles per ml to 11.4 +/- 2.3 fmoles per ml) was blunted (p less than 0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis.

Improved sexual function in hemodialysis patients on recombinant erythropoietin: a possible role for prolactin.

As it was reported that correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) is associated with improved sexual function, we conducted the present study to further delineate the mechanism(s) by which this is brought about. Serum prolactin, testosterone, and parathyroid hormone (PTH) levels were followed during 4 months of r-HuEPO therapy. Within 4 months of treatment with r-HuEPO, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin increased from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were low in male patients and remained unchanged during r-HuEPO therapy. Baseline PTH values were elevated (1,880 +/- 220 pg/ml) in patients of both sexes and declined to 1,410 +/- 180 pg/ml during treatment with r-HuEPO. However, this difference did not reach statistical significance. Sexual function improved in 4 out of 7 males and 5 out of 9 female patients began to menstruate regularly again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO improves sexual function via normalization of elevated serum prolactin concentrations.

Drug-induced changes in prolactin secretion. Clinical implications.

Prolactin secretion is affected by various diseases as well as by many drugs in humans and animals. While marked hyperprolactinaemia suggests the presence of a pituitary tumor, moderate changes may also occur in various endocrine or non-endocrine disorders. Drugs can interfere with prolactin regulation via complex mechanisms at the hypothalamus or at the pituitary site, but possible changes in prolactin metabolism are poorly understood as yet. This survey of the literature up to June 1986 covers the influence of various groups of drugs and agents on the plasma prolactin level under various conditions. It contains information that will facilitate evaluation of whether hyper- or hypoprolactinaemia may result from therapeutic intervention or must be related to an underlying disease. It is obvious that more subtle changes can be revealed by the use of dynamic tests either to stimulate or to suppress prolactin secretion.

Role of atrial natriuretic factor, cyclic GMP and the renin-aldosterone system in acute volume regulation of healthy human subjects.

The role of the atrial natriuretic factor (ANF), its second messenger cyclic guanosine monophosphate (cGMP), and the counteracting renin-aldosterone system in acute volume regulation was investigated in 25 healthy human subjects. Central volume stimulation by 1-h head-out water immersion (WI) into a thermoneutral water-bath increased plasma levels of ANF (mean +/- SEM) from 6.0 +/- 0.6 to 13.6 +/- 2.6 fmol ml-1. This was paralleled by a rise of plasma cGMP levels from 1.9 +/- 0.2 to 2.8 +/- 0.4 pmol ml-1, and an increase of urinary cGMP excretion from 340 +/- 64 to 692 +/- 103 pmol min-1. Water immersion reduced plasma aldosterone concentration (PAC) from 13.0 +/- 1.7 to 6.5 +/- 0.8 ng 100 ml-1 and plasma renin activity (PRA) from 5.3 +/- 0.9 to 2.4 +/- 0.3 ng AI ml-1 h-1. Volume stimulation markedly increased diuresis and natriuresis. Whereas the plasma cGMP increase correlated with plasma ANF stimulation, neither ANF nor PRA or PAC correlated with basal or stimulated renal parameters. Water immersion-induced changes in natriuresis and urinary cGMP excretion were correlated. These data suggest a role of ANF and cGMP in acute volume regulation of healthy human subjects.

Renin-angiotensin system, blood pressure homeostasis and renal function in galactosamine-induced fulminant hepatic failure in the guinea pig.

Arterial blood pressure, renal function and plasma concentrations of renin and renin substrate (angiotensinogen) were investigated in guinea pigs subjected to galactosamine-induced (1 g/kg i.v.) liver cell necrosis. Blood pressure declined continuously by 50% during a follow-up period of 72 h which was associated with a decrease in diuresis and natriuresis to 36 and 31%, respectively. Simultaneously, plasma renin concentration increased 30-fold indicating marked reduction of renal perfusion, while plasma renin substrate concentration fell to 6% of the baseline level. There was microscopic evidence of oligemic circulatory renal damage characterized by acute proximal tubular necrosis with concomitant tubular dilatation. Short-term infusion of homologous renin substrate-enriched plasma, derived from nephrectomized animals, was followed by marked increase in mean arterial blood pressure from 34 +/- 9 to 77 +/- 7 mm Hg accompanied by marked diuresis and natriuresis. Renin substrate depletion following galactosamine-induced fulminant liver failure may represent impaired hepatic biosynthesis as well as increased renin substrate consumption due to excessive renin secretion. Angiotensinogen repletion has a beneficial effect on both renal function and blood pressure probably due to marked generation of the potent vasoconstrictor angiotensin II which consequently inhibits renin secretion. These observations strongly support the suggestion that the renin-angiotensin system is of major importance to cardiovascular homeostasis in acute liver failure.

Interrelationship between atrial natriuretic peptide and plasma renin, aldosterone and catecholamines in hepatic cirrhosis: the effect of passive leg rising.

To assess the role of atrial natriuretic peptide (ANP) in relation to the sympathoadrenal and renin-angiotensin-aldosterone system, and sodium excretion, 88 cirrhotic patients (mean age 52 years; 28 compensated, 28 decompensated with ascites, and 32 decompensated and treated with diuretics) and 26 control subjects were investigated. Basal ANP levels were not different between any group of cirrhotics and controls. Circulating ANP was not related to elevated plasma noradrenaline and adrenaline, and enhanced plasma renin/aldosterone levels in ascitic patients. Furthermore, ANP was not related to urinary sodium excretion, blood pressure, and heart rate. In 30 cirrhotic patients (12 compensated, 18 decompensated with ascites including eight on diuretic therapy) and nine controls, a passive leg rising procedure for 1 h was performed in order to augment central blood volume and atrial pressure physiologically. Ascitic patients (with and without diuretic treatment) experienced a slight but significant increase in plasma ANP indicating preserved responsiveness of ANP release in cirrhosis. Plasma aldosterone was markedly depressed. The data support the underfilling concept of ascitic formation in advanced stages of cirrhosis. The failure of enhanced ANP release under basal conditions may be due to the diminished effective blood volume, resulting in insufficient atrial stretching.

Plasma free and sulfoconjugated catecholamines during acute asphyxia in the sheep fetus--relation to cardiovascular parameters.

Changes of free and sulfoconjugated catecholamines were measured radioenzymatically during a 5 minute period of acute asphyxia in chronically instrumented sheep fetuses (n = 5). Due to total reduction of uterine blood flow asphyxia as well as metabolic acidosis developed (pH = 6.94 +/- 0.02; Pco2 = 98 +/- 8 mmHG; lactate = 7.1 +/- 0.3 mmol/l). Peak concentrations of free catecholamines were reached after 3 minutes; free NE increased 60-fold, free E 370-fold and free DA 13-fold as compared to control values. Concomitantly, sulfoconjugated catecholamines rose markedly and were 40-fold (NE), 300-fold (E) and 10-fold (DA) higher when compared to the control period. Thus, the results reveal that the fetal sulfoconjugating system is very effective and able to match high concentrations of free catecholamines entering the circulation. After release of occlusion, free and sulfoconjugated catecholamines decreased with a half life time of 2.5 to 4.3 minutes during the initial 10 minutes. A close correlation could be demonstrated between free catecholamines and fetal arterial blood pressure, however, with interference of the effects of desoxygenation on the myocard. Moreover, fetal tachycardia is related to circulating catecholamines, especially E, during the postasphyxial period. Our results suggest, that in unstressed, normoxic fetuses the cardiovascular system is able to maintain basic functions (heart rate and blood pressure) during asphyxia for 5 minutes. In this context, a maximal sympathoadrenal stimulation with secretion of free catecholamines seems to be essential.

[Abdominal sonography in hereditary angioneurotic edema. A contribution to the early diagnosis of a disease of interdisciplinary significance]. / Abdominelle Sonographie bei hereditärem angioneurotischem Odem. Ein Beitrag zur Frühdiagnose einer interdisziplinär bedeutsamen Erkrankung.

Hereditary angioneurotic oedema is a rare complement-related disorder (C1-esterase-inhibitor deficiency) characterised by recurrent episodic swelling of the limbs, face, gastrointestinal tract, or airways. The mortality rate of the unrecognised disorder is 30 per cent, mainly due to airway obstruction. Two female patients (aged 29 and 61 years) with proven disease were studied by ultrasonography while they suffered from acute abdominal pain: Ultrasound imaging showed a diffuse oedematous but compressible gut wall with reduced bowel motility, distended bowel loops with intraluminal fluid accumulation and free fluid in the peritoneal cavity. The ultrasonographic feature was different from that of other gastrointestinal diseases. In combination with the patient's history, the clinical pattern and the normal routine laboratory findings, abdominal ultrasonography is a suitable tool for early diagnosis of a potentially life-threatening disorder.