6-phosphogluconate dehydrogenase: hemizygous manifestation in a patient with leukemia.

In a study of 41 patients with chronic myelocytic leukemia, two were found to have the 6-phosphogluconate dehydrogenase heterozygous phenotype A-B, and two had the phenotype characteristic of Pd(B) homozygosity. Since one of the two with Pd(B) homozygosity was the mother of two children with the A phenotype, it was presumed that she carried a Pd(A) gene not expressed in her blood cells. his was confirmed by electrophoretic analysis of her fibroblasts, which had the A-B phenotypic pattern. Gene deletion is considered to be the most likely explanation.

Hypothalamic-pituitary-gonadal function in patients with myotonic dystrophy.

Gonadal function was studied in three post-pubertal siblings (two male and one female) and one unrelated male patient with myotonic dystrophy. The diagnosis was confirmed in all cases by electromyography and muscle biopsy. Basal levels of plasma immunoreactive LH, FSH, testosterone, and estradiol were measured. Hypothalamic, pituitary, and gonadal reserve and responsiveness were evaluated by clomiphene, LHRH, and HCG tests. Histologic examination of gonadal biopsies was also performed. The results showed that gonadal failure present in the four patients had different characteristics. In the same family, hypothalamic amenorrhea was observed in the female patient, and hypothalamic eunuchoidism and hypergonadotropic hypogonadism with marked tubular and leydig cells failure in the male patients. The non-related male patient had hypergonadotropic hypogonadism with tubular failure but with a compensatory leydig-cell hyperplasia. These data are interpreted as demonstrating different expressivity of the hypogonadism associated with the same inherited muscle disease.

Familial incomplete virilization due to partial end organ insensitivity to androgens.

A 16-yr-old 46 XY individual with a familial incomplete male pseudohermaphroditism closely resembling the syndrome described by Gilbert-Dreyfus et al. was studied. The patient's habitus was masculine despite the presence of a small phallus, pseudo-vaginal perineal hypospadias, bifid scrotum, gynecomastia, and diminished virilization. Blood samples obtained at 20-min intervals were submitted to hormone analysis. Episodic fluctuations of plasma gonadotropins with mean values of LH above the normal male range and FSH within normal limits were observed. Moderately elevated plasma testosterone and increased plasma estradiol also showed episodic oscillations. The administration of LH-releasing hormone resulted in a significative increase of plasma LH and FSH. Testicular biopsy revealed the presence of seminiferous tubules with few spermatogonia and no spermatocytes, and normal sertoli and interstitial cells. Gonadal stimulation with hCG for 4 consecutive days induced a significative increase of plasma testosterone and estradiol. The daily administration of 50 mg of testosterone propionate for 3 days neither depressed the circulating levels of gonadotropins nor modified the pulsatile pattern of gonadotropins release. Administration of testosterone and 5alpha-dihydrotestosterone propionate failed to diminish plasma LH and FSH levels. Testosterone administration for 10 weeks also failed to induce virilization. These results are similar to those observed in patients with testicular feminization syndrome, and the underlying abnormality involves a partial defect of the mechanism of action of testosterone rather than decreased androgen biosynthesis. According to a recently proposed classification this individual corresponds to the type 1 incomplete male pseudohermaphroditism.

A new inherited variant of the 3 beta-hydroxysteroid dehydrogenase-isomerase deficiency syndrome: evidence for the existence of two isoenzymes.

The clinical and endocrine features of a unique form of adrenal insufficiency secondary to an inherited deficiency of 3 beta-hydroxysteroid dehydrogenase-isomerase (3-HSD) were studied. The propositus was a 19-yr-old man with a history of repeated episodes of acute adrenal crisis. Family study disclosed that a 6-yr-old female sibling also was affected, and a third sibling had died during the course of an adrenal crisis. The diagnosis of adrenal insufficiency was established on the basis of extremely low serum cortisol levels and urinary 17-hydroxycorticosteroid excretion with concomitantly elevated serum ACTH levels and lack of cortisol response to ACTH administration. Impairment of C-21 steroid 3-HSD activity was strongly suggested by persistency elevated serum 17-hydroxypregnenolone to 17-hydroxyprogesterone and pregnenolone to progesterone ratios, their significant increase after ACTH administration, and their return to normal during cortisol therapy in both patients. Nevertheless, the serum dehydroepiandrosterone to androstenedione ratio, both basally and after ACTH and/or hCG stimulation, was normal. These findings coupled with the normal phenotypic development and onset of puberty in the two patients indicated intact C-19 steroid 3-HSD activity. The overall results indicate an inherited impairment of 3-HSD activity confined only to C-21 steroid substrates and, thus, suggest the existence of at least two 3-HSD isoenzymes under independent genetic regulation.

Intestinal lactase deficiency and milk drinking capacity in the adult.

The milk drinking capacity of 200 adults was determined experimentally and the results correlated with their milk drinking habits and intestinal lactase activity as judged by a lactose tolerance test. Of the group 65.5% were found to have deficient lactase activity and 5.3% experienced severe gastrointestinal symptoms with 250 ml of milk; 28.2% with 500 ml; 26.0% with 750 ml; 15.3% with 1000 ml and 25.2% tolerated the latter amount without difficulty. Of the normal individuals, 92.7% tolerated 1000 ml without symptoms. Intestinal lactase activity seemed to be important in determining the extremes of milk ingestion: four or more glasses per day or no milk ingestion, but had little effect in the intermediate pattern of milk consumption. It is concluded that intestinal lactase deficiency has clinical relevance and should be considered when nutritional supplementation with milk is contemplated.

Double blind study of milk lactose intolerance in a group of rural and urban children.

Two-hundred forty rural and 101 urban children were studied in a double blind fashion to determine their clinical response to three types of milk. Each participant received in three different days, 250 ml of lactose free milk, regular milk, and lactose enriched milk. In the urban girls a control period in which no milk was given was included. In both study groups, lactose free milk was highly significantly better tolerated than the others. However, the frequency of subjects asymptomatic after its ingestion was much lower, particularly in the rural group, to that found previously in a group of adults of high socioeconomic status. It is thought that in the rural children, part of this phenomenon can be explained by intercurrent gastrointestinal infections. There also appears to be a "background" of gastrointestinal symptoms present in the children, which wrongly classifies them as symptomatic to milk ingestion. It is concluded that probably no less than 15% of children have gastrointestinal complaints after the ingestion of 250 ml of regular milk and that lactose hydrolyzed milk is highly significantly better tolerated than the others.

Attitudes of Mexican geneticists towards prenatal diagnosis and selective abortion.

Prenatal diagnosis (PD) provides the physician information on whether the unborn fetus has a genetic or chromosomal disorder, and offers patients a new option: selective abortion. In the present study, we analyzed the answers Mexican geneticists provided to a few selected questions from a multinational survey designed by Wertz and Fletcher [1988: Am J Hum Genet 42:592-600]. The selected questions were related to the use of PD, the acceptance of selective abortion, and the self-reported directiveness of counselling following the diagnosis of a fetal anomaly. Our results show that the great majority of Mexican geneticists participating in the study agree with PD when medically indicated, but not on free demand. Specific cases stimulated the group on thinking more than the general statements provided in the survey. Although the majority agreed that PD should be available to all women, when faced with cases of nonmorbid maternal anxiety, paternity testing, and sex selection, the proportion of geneticists willing to perform the test decreased substantially. When counselling patients on a fetal anomaly, the minority would be as unbiased as possible, and this seems to be the tendency in developing countries where counselling, as stated in the respondents' comments, reflects the belief that the goal of genetics is the prevention of or opposition to abortion. Counselling was influenced by the severity of the disorder. The geneticists' personal attitude toward abortion in the same situations was stronger than when counselling others. Analysis of directiveness in counselling for fetal anomaly showed that older geneticists, with more years of experience in medical genetics, were more likely to be neutral. When counselling directively, the group showed an overall direction toward continuing affected pregnancies. However, older geneticists and those with more than 10 years of practice were more likely than their younger counterparts to counsel towards terminating affected pregnancies. In personal situations of fetal disorder, the general tendency was to abort; however, geneticists seeing more than 5 patients per week, and those who believe that religion is important, were more likely to reject abortion. The sample is representative of Mexican geneticists, and the main limitation of this study is that the geneticists have very little experience in PD, and that their responses were mostly based on theory. However, their opinions may influence the demand and the availability of PD and abortion, as well as the possibility of legalization of abortion on the basis of a fetal defect.

Counselling following diagnosis of a fetal abnormality: comparison of different clinical specialists in Mexico.

Most geneticists agree that counselling should be nondirective, and studies report that genetic counselling by geneticists is performed largely in a neutral style. However, couples at risk of having a child with a genetic condition may seek the advice of other physicians. The purpose of the present study was to describe the answers of four groups of specialists from Mexico City (internists, pediatricians, obstetricians, and neurologists) regarding how they would counsel a couple when prenatal diagnosis has shown that a fetus is affected by one of 17 different genetic disorders and to analyze the role of several variables in the development of their opinion. Our results show that physicians in these specialties are more likely to counsel directively than neutrally. Other variables did not influence the directiveness. With respect to direction of influence, internists, pediatricians, and neurologists are more likely to counsel terminating affected pregnancies than are obstetricians (P = 0.0002). Similarly, clinicians older than 37 years of age and those reporting that religion is not important to them counsel terminating affected pregnancies (P = 0.005 and P = 0.003, respectively). Physicians' gender and clinical experience with genetic diseases did not show statistically significant differences. Strong consensus among specialists was reached only on terminating pregnancies in anencephaly. A lowered and moderate consensus (51-75% agreement) was reached on continuing pregnancies with cleft lip and plate. A moderate measure of consensus for nondirective counselling was found among obstetricians regarding 14 of the 17 diseases in the study, whereas neurologists expressed a moderate measure of consensus on counselling the termination of pregnancies when the fetus was affected by neurological disorders. Hence, the approach to counselling was related in part to the fetal condition and in part to the clinician's specialty and age and the self-reported importance of religion. The data presented herein may not be representative of all Mexican physicians within the selected specialties; however, it is important to gather their opinions because they are involved in the care and treatment of genetic diseases and may have an important influence on the demand and availability of prenatal diagnosis and abortion.

Duplication 11q and deletion 5p syndromes due to a reciprocal translocation segregating in four generations.

We report on 2 relatives with duplication 11q and deletion 5p, resulting from an adjacent-1 segregation of a balanced reciprocal translocation 5p15;11q23, segregating in 4 generations of this family. Twelve out of 16 at-risk relatives of inheriting the translocation were shown to be carriers, giving a significant (p less than .05) 3:1 ratio of carriers/noncarriers. The breakpoint on chromosome 11 at q23 is a folate sensitive fragile site into where the proto-oncogene c-ets has been mapped.

Gerodermia osteodysplastica hereditaria: report of three affected brothers and literature review.

Gerodermia osteodysplastica hereditaria was diagnosed in three Mexican brothers 6, 7, and 8 years old, respectively, who had the distinct facial appearance with sagging cheeks, premature wrinkling of the skin of face, abdomen, and dorsum of hands and feet; malocclusion, span greater than height; hyperextensibility; winging of the scapulae; stooped posture with kyphoscoliosis; protuberant abdomen; and pes planus. Radiologically they had generalized osteoplorosis, platyspondily due to multiple compression fractures, pseudoepiphyses of second metacarpals, and dislocated hips. Three other families with a total of 14 affected individuals have been reported. Inter- and intrafamilial variability can be recognized, particularly regarding the tendency to fractures, upper:lower segment ratio abnormalities, and results of skin biopsies, which have shown fragmentation of the elastic fibers in some cases (including the present family) and not in others. Although inheritance was considered to be X-linked recessive in the first reported family, an analysis of that pedigree together with those of the other reported families, including the present one, suggests that gerodermia osteodrysplastica is inherited in an autosomal recessive manner.

Peripheral motor neuropathy associated with autonomic dysfunction in two sisters: new hereditary syndrome?

We describe two sisters with distal, slowly progressive muscular weakness and hypotrophy since childhood, autonomic dysfunction characterized by profuse sweating, distal cyanosis related to cold weather, orthostatic hypotension, and esophageal achalasia. Nerve conduction velocity of several motor nerves was slow, and although no sensory abnormalities were present, sural nerve biopsy revealed severe nonspecific demyelination. No similar patients could be found in the literature and we therefore suggest the possibility that these individuals have a newly recognized hereditary syndrome.

Fetal mortality in sibships with one or more affected members with oral clefts.

We investigated the fetal mortality in 903 sibships with at least one member having cleft lip with or without cleft palate [CL(P)] and 213 with at least one individual affected with cleft palate (CP) derived from three different data sources in México. The frequency of fetal wastage (abortion and/or stillbirth) was not increased in sibships where the propositi had cleft lip and palate (CLP) as compared with cleft lip (CL) nor in those where index cases had a bilateral lesion as compared to a unilateral one, nor when the index cases with CL(P) were female rather than males, nor when the index case was a female with bilateral lesion as compared to males with a unilateral one. Similarly fetal mortality was not increased in sibships in which the propositus had CP compared to those in which the index case was a female. These findings are contrary to some reports that claim to support a two-threshold model according to which individuals reaching the first one would be born with an oral cleft, and those reaching the second would be aborted. Our results, together with others, suggest the possibility that liability to oral clefts is independent of liability to fetal wastage.

Molecular differentiation of two different translocations producing two apparent Ph chromosomes in a patient with CML.

A case of chronic myelogenous leukemia (CML) is described whose leukemic cells appeared to contain two Philadelphia (Ph) chromosomes originating from different translocations involving the two chromosomes 22. The karyotype of the affected cells, established on two different occasions, was: 46,XY,t(9;22)(q34;q11),t(15;22)(p11;q11) with no normal chromosomes 22 and only one 9q+ in each of 115 marrow cells examined. The same findings were present in 50 peripheral blood cells cultured without phytohemagglutinin (PHA) stimulation. When stimulated with PHA, a normal male karyotype was present in the 11 cells examined. There were no additional chromosomal abnormalities and no indication of a blastic crisis after nearly 1 year following the original study. Analysis of the breakpoint cluster region (bcr) on chromosome 22 in the DNA of the affected cells (marrow) revealed evidence for one rearranged chromosome 22 and one normal chromosome 22, indicating that the t(15;22) was not due to the usual Ph translocation seen in CML. The results point to the crucial usefulness of molecular analysis in confirming cytogenetic results related to Ph translocations in CML.

Sister-chromatid exchanges and cell kinetics in human and rabbit lymphocytes exposed in vivo and in vitro to 2-bromo-alpha-ergocryptine.

The possible mutagenic and DNA-synthesis inhibitory effects of 2-bromo-alpha-ergocryptine, a new semi-synthetic ergot alkaloid, was studied in human and rabbit lymphocytes exposed to it in vivo and in vitro. The analysis of SCE was mainly used to evaluate potential mutagenicity, and the mitotic and DNA-synthesis inhibition was explored by examining the proportions of first-, second- and third-division metaphases in the corresponding lymphocyte cultures. The results obtained show that 2-bromo-alpha-ergocryptine does not induce SCE in the cell systems tested, or structural chromosome aberrations in human lymphocytes in vivo. On the other hand, a marked mitotic inhibitory effect and associated cell kinetic changes could be clearly attributed to the drug, probably related to its cytotoxicity.

Blood groups and red cell acid phosphatase types in a Mixteca population resident in Mexico City.

Several blood groups, ABO, Rh, Ss, Fy, Jk, and red cell acid phosphatase (ACP) types were studied in a native Mixteca population that has resided in Mexico City since 1950. Gene frequencies were obtained and used to establish admixture estimates with blacks and whites. The subjects came from three different geographical areas: High Mixteca, Low Mixteca, and Coast Mixteca. All frequencies were in Hardy-Weinberg equilibrium. The difference in the ABO frequencies was statistically significant when subjects from the three areas were compared simultaneously. Rh frequencies differed only between the High and the Low Mixteca populations. The ACP frequencies were similar between the Low Mixteca population and a previously reported Mestizo population. However, there were significant differences between the High Mixteca group and a Mestizo population, all the subjects being from Oaxaca. This is the first report of Ss, Fy, Jk, and ACP frequencies in a Mixteca population. Am. J. Hum. Biol. 11:525-529, 1999. Copyright 1999 Wiley-Liss, Inc.

Attitudes of Mexican physicians toward induced abortion.

The objective of this study was to analyze physicians' attitudes towards induced abortion with normal fetuses and fetuses known to have an abnormality in various degrees. A total of 193 physicians (internists, pediatricians, gynecologists and neurologists) answered a self-administered questionnaire. The questions were about voluntary abortion; voluntary abortion with malformed fetus; abortion because the fetus has anencephaly; and two questions were asked for the use of prenatal diagnosis and abortion in case of the fetus being the physician's child. The majority of physicians were male, over 35 years, religious and did not have experience with genetic diseases. Few physicians approved abortion of a normal pregnancy, 6 out of 10 agreed if the fetus was malformed, and this number increased to 8 or 9 out of 10 in cases of severe or lethal genetic disease. Gynecologists and neurologists were less in agreement with abortion when pregnancy is normal than the internists and pediatricians (7% vs. 20%). In general the physicians did not have consistent answers. Agreement for abortion was influenced by religious values.

[The Philadelphia chromosome 30 years later]. / El cromosoma Filadelfia 30 años después.

We review the changing concepts regarding the nature of the Ph chromosome during the last thirty years. The role of molecular biology techniques in its identification are discussed as well as its present status in the diagnosis, prognosis and management of chronic myelogenous leukemia and acute lymphoblastic leukemia.

[Overview of erythrocyte glucose-6-phosphate deficiency]. / Panorama de la deficiencia de la glucosa-6-fosfato deshidrogenasa eritrocítica.

The cloning and sequencing of the G6PD gene has opened a new chapter in the characterization of the numerous G6PD variants described. Many which were thought to be different on the basis of their kinetic properties, are really the same whereas heterogeneity has been found in some which were thought to be homogeneous. We discuss with some detail variants A+, A- and the Mediterranean type.

[Heredity of poor digestion of lactose]. / Herencia de la mala digestión de lactosa.

The published reports on the possibility that the adult type of lactose maldigestion is a hereditary condition are reviewed. The ethnic variability in the frequency of this trait, together with twin and family studies, suggest that this is indeed the case. Family studies, including the one performed in Mexico, indicates that the adult type of lactose maldigestion is inherited in an autosomic recessive manner.

[Familial polyposis of the colon. Analysis of 17 cases]. / Poliposis familiar del colon. Análisis de 17 casos.

Seventeen cases of familiar polyposis of the colon seen in the National Institute of Nutrition are reviewed. In 12 of the cases (70%) there were family histories of colonic polyposis. Ten patients (50%) developed carcinoma and of these 7 were located in the rectosigmoide. Ten patients underwent total colectomy with abdominoperineal resection. Seven already had carcinoma at operation; 5 localized and with survival rates of more than 5 years without evidence of recurrence; the other 2 had distant metastasis at operation. Four patients underwent colectomy with ileoproctoanastomosis. In 2 of these cases subsequent abdominoperineal resection was necessary; another died of recurrent carcinoma and the fourth is alive and asymptomatic. Familiar colonic polyposis is an hereditary disease of the autosomic dominant type with a tendency to develope malignant changes at an early age. The treatment of choice is colectomy; however, controversy exists as to whether or not the rectum should be conserved. Based on our results, and those of other authors, we feel that the treatment of choice is total colectomy with abdominoperineal resection, because of the high probability of malignant recurrence.