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Consanguinity in two seemingly unrelated patients with congenital adrenal hyperplasia
showed pronounced bilateral lesions in the thalamus, the cerebral peduncles, and the left caudate nucleus without
(figure). During the next few weeks neurological signs slowly improved. A follow-up MRI 17 days after admission revealed a slight regression of the aforementioned lesions. At the time of discharge from hospital, 21 days after admission, the patient was able to communicate, but had a 4/5 grade paresis of the left arm, and slight facial palsy on the left side. During the next weeks contrast enhancement
her condition further improved, but she died from a pulmonary embolism 10 weeks after transfer to her local
hospital. The localisation of the MRI abnormalities corresponded well with neuropathological reports of severe lesions in the thalamus and basal ganglia in TBE.2 In addition, clinical reports of an extrapyramidal tremor in 75-5% of 679 patients with TBE suggested that basal ganglial involvement is a common
phenomenon in TBE.’
S Lorenzl, H W Pfister, C Padovan, T
Yousry
Department of Neurology and Radiology, Klinikum Großhadern, Ludwig-Maximlians-University of Munich, D-81377 Munich, Germany
1 Kaiser R. Tick-borne encephalitis in southern Germany. Lancet 1995; 345: 463. 2 Jellinger K. The histopathology of tick-borne encephalitis. In: Kunz TH, ed. Tick-borne encephalitis. Vienna: Facultas Verlag, 1981: 59-75. 3 Duniewicz M. Clinical picture of central European tick-borne encephalitis. Münch Med Wschr 1976; 118: 1609-12.
origin of the patients’ two families respectively. However, no common ancestor was discovered until the ninth (patient 1) and llth (patient 2) previous Figure:
Area of
generations. Since this roughly coincides with the period of the 30-years war, the genetic information causing 21hydroxylase deficiency has been preserved in these two individuals for more than 300 years, resulting in an unexpected family reunion in an endocrine outpatient department. Supported in part by grant P 10110-Med from the Austrian Fonds Forderung der Wissenschaftlichen Forschung.
zur
*H Vierhapper, M S Vierhapper, K Kapelari, Sabina Baumgartner-Parzer, R Kofler *Division of Endocrinology and Metabolism, Department of Internal Medicine, of Vienna, 1090 Vienna, Austria; and Department of Molecular Biology, of Innsbruck
University University
Consanguinity in two seemingly unrelated patients with congenital adrenal hyperplasia SiR-Two female patients, born in 1976 (patient 1) and 1980 (patient 2), with an identical family name, were referred to our outpatient department for evaluation of possible congenital adrenal hyperplasia. Both patients were called Alexandra, a name given to 5-4% of female Austrian babies when these patients were born. The two patients did not know of each other’s existence, patient 1 having been bom in Vienna and patient 2 in a small village about 150 km northwest of Vienna. Their parents were also unaware of the other family. Clinical examination, plasma concentrations of 17-OHand testosterone (measured progesterone by and 16-3-855 nmol/L, patients 1 radioimmunoassay) (1381 and 2, respectively), urinary steroid excretion rates (capillary gas-chromatography’); and the pregnantriol/tetrahydro-cortisone ratio’ 31-0 and 1-0-39-0, respectively) confirmed the presence of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in both patients. HLA typing showed one identical allele (A26,B47,Cw6; DR7,DRB4,DQ2) in both patients. Molecular biological analysis2 from blood samples obtained from the patients and their parents showed the following defects: patient 1, V281L mutation of the CYP21B gene and deletion of the CYP21B gene on both maternal and paternal chromosome, respectively; patient 2, complete deletion of the CYP21B gene on both paternal and maternal chromosomes. There was no apparent difference in the genetic defects inherited by the patients from their fathers. These results suggest with a very high probability that the two girls are related to each other. No other member of either family was or is known to have 21-hydroxylase deficiency. The patients’ families were retraced to a possible common area of origin in northwestern Czechia (formerly Austrian Silesia; figure), from where they had migrated to their present home towns around 1850 and 1890,
1
Vierhapper H, Nowotny P, Waldhäusl W, Frisch H. Capillary gas chromatography as a tool for characterization of urinary steroid excretion in patients with congenital adrenal hyperplasia. J Steroid Biochem
2
1985; 3: 363-69. Helmberg A, Tabarelli M, Fuchs MA, et al. Identification of molecular defects causing congenital adrenal hyperplasia by cloning and differential
hybridization of polymerase chain reaction-amplified 21-hydroxylase (CYP21) genes. DNA Cell Biol 1992; 11: 359-68.
Pre-endoscopy screening for helicobacter prospective study by Patel and 18, (Nov 1315)1 colleagues p looking at helicobacter as a serology pre-endoscopy screening test. However, the 36% saving on endoscopies is, we feel, a generous suggested estimate on two accounts. First, patients who were screened negative, were not endoscoped, and did not return their questionnaire, were classified as endoscopies saved. Although this grouping may be correct, it could equally be true that this group were endoscoped elsewhere. On the assumption that all these patients were endoscoped, the number of investigations saved in this study falls from 67 to 54, or 29-5% of patients under 45. Second, we recognise, as SiR-We welcome the first
do Patel and co-workers, that 6 months is insufficient time establish whether an endoscopy has actually been saved
to
or
merely postponed.
With respect to the service as a whole, it is relevant to emphasise that Patel et al do not specify what proportion of the population who undergo endoscopy with biopsy are under 45 years. In a district general hospital setting in midEssex, this proportion is 28% (212/750) at most. Overall savings in endoscopies in this district at best will be between 29-5 and 36-0% on this figure-ie, 8-10%, which more accurately represents the best one might expect to achieve by the use of serological testing to screen in this way, although it does not detract from our support for this approach. Nationally, savings on endoscopies would be 699
(figure). During the next few weeks neurological signs slowly improved. A follow-up MRI 17 days after admission revealed a slight regression of the aforementioned lesions. At the time of discharge from hospital, 21 days after admission, the patient was able to communicate, but had a 4/5 grade paresis of the left arm, and slight facial palsy on the left side. During the next weeks contrast enhancement
her condition further improved, but she died from a pulmonary embolism 10 weeks after transfer to her local
hospital. The localisation of the MRI abnormalities corresponded well with neuropathological reports of severe lesions in the thalamus and basal ganglia in TBE.2 In addition, clinical reports of an extrapyramidal tremor in 75-5% of 679 patients with TBE suggested that basal ganglial involvement is a common
phenomenon in TBE.’
S Lorenzl, H W Pfister, C Padovan, T
Yousry
Department of Neurology and Radiology, Klinikum Großhadern, Ludwig-Maximlians-University of Munich, D-81377 Munich, Germany
1 Kaiser R. Tick-borne encephalitis in southern Germany. Lancet 1995; 345: 463. 2 Jellinger K. The histopathology of tick-borne encephalitis. In: Kunz TH, ed. Tick-borne encephalitis. Vienna: Facultas Verlag, 1981: 59-75. 3 Duniewicz M. Clinical picture of central European tick-borne encephalitis. Münch Med Wschr 1976; 118: 1609-12.
origin of the patients’ two families respectively. However, no common ancestor was discovered until the ninth (patient 1) and llth (patient 2) previous Figure:
Area of
generations. Since this roughly coincides with the period of the 30-years war, the genetic information causing 21hydroxylase deficiency has been preserved in these two individuals for more than 300 years, resulting in an unexpected family reunion in an endocrine outpatient department. Supported in part by grant P 10110-Med from the Austrian Fonds Forderung der Wissenschaftlichen Forschung.
zur
*H Vierhapper, M S Vierhapper, K Kapelari, Sabina Baumgartner-Parzer, R Kofler *Division of Endocrinology and Metabolism, Department of Internal Medicine, of Vienna, 1090 Vienna, Austria; and Department of Molecular Biology, of Innsbruck
University University
Consanguinity in two seemingly unrelated patients with congenital adrenal hyperplasia SiR-Two female patients, born in 1976 (patient 1) and 1980 (patient 2), with an identical family name, were referred to our outpatient department for evaluation of possible congenital adrenal hyperplasia. Both patients were called Alexandra, a name given to 5-4% of female Austrian babies when these patients were born. The two patients did not know of each other’s existence, patient 1 having been bom in Vienna and patient 2 in a small village about 150 km northwest of Vienna. Their parents were also unaware of the other family. Clinical examination, plasma concentrations of 17-OHand testosterone (measured progesterone by and 16-3-855 nmol/L, patients 1 radioimmunoassay) (1381 and 2, respectively), urinary steroid excretion rates (capillary gas-chromatography’); and the pregnantriol/tetrahydro-cortisone ratio’ 31-0 and 1-0-39-0, respectively) confirmed the presence of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in both patients. HLA typing showed one identical allele (A26,B47,Cw6; DR7,DRB4,DQ2) in both patients. Molecular biological analysis2 from blood samples obtained from the patients and their parents showed the following defects: patient 1, V281L mutation of the CYP21B gene and deletion of the CYP21B gene on both maternal and paternal chromosome, respectively; patient 2, complete deletion of the CYP21B gene on both paternal and maternal chromosomes. There was no apparent difference in the genetic defects inherited by the patients from their fathers. These results suggest with a very high probability that the two girls are related to each other. No other member of either family was or is known to have 21-hydroxylase deficiency. The patients’ families were retraced to a possible common area of origin in northwestern Czechia (formerly Austrian Silesia; figure), from where they had migrated to their present home towns around 1850 and 1890,
1
Vierhapper H, Nowotny P, Waldhäusl W, Frisch H. Capillary gas chromatography as a tool for characterization of urinary steroid excretion in patients with congenital adrenal hyperplasia. J Steroid Biochem
2
1985; 3: 363-69. Helmberg A, Tabarelli M, Fuchs MA, et al. Identification of molecular defects causing congenital adrenal hyperplasia by cloning and differential
hybridization of polymerase chain reaction-amplified 21-hydroxylase (CYP21) genes. DNA Cell Biol 1992; 11: 359-68.
Pre-endoscopy screening for helicobacter prospective study by Patel and 18, (Nov 1315)1 colleagues p looking at helicobacter as a serology pre-endoscopy screening test. However, the 36% saving on endoscopies is, we feel, a generous suggested estimate on two accounts. First, patients who were screened negative, were not endoscoped, and did not return their questionnaire, were classified as endoscopies saved. Although this grouping may be correct, it could equally be true that this group were endoscoped elsewhere. On the assumption that all these patients were endoscoped, the number of investigations saved in this study falls from 67 to 54, or 29-5% of patients under 45. Second, we recognise, as SiR-We welcome the first
do Patel and co-workers, that 6 months is insufficient time establish whether an endoscopy has actually been saved
to
or
merely postponed.
With respect to the service as a whole, it is relevant to emphasise that Patel et al do not specify what proportion of the population who undergo endoscopy with biopsy are under 45 years. In a district general hospital setting in midEssex, this proportion is 28% (212/750) at most. Overall savings in endoscopies in this district at best will be between 29-5 and 36-0% on this figure-ie, 8-10%, which more accurately represents the best one might expect to achieve by the use of serological testing to screen in this way, although it does not detract from our support for this approach. Nationally, savings on endoscopies would be 699