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Aim: To appraise the economic burden for families of patients with type 1 diabetes mellitus (DM1) at the Instituto Nacional de Pediatria in Mexico City., Patients and Methods: DM1 family direct costs were obtained from a standardized economic survey in 59 children with no chronic severe complications such as kidney failure in 2002-3., Results: Mean family annual direct cost of treatment and monitoring was US $1689.87 which includes government funding given to both outpatients and inpatients. Despite this, DM1 out-of-pocket cost for families is very high compared to the minimum official wage of approximately $4.00 dollar/day versus $4.06 cost DM1/day. No correlation between parents' age, education or socio-economic level and direct cost was statistically significant., Conclusions: The highest economic burden was due to self-monitoring of blood glucose (SMBG) 53.0% and insulin 14.8%. The costs were higher in children with poor metabolic control who performed SMBG less often.

Context: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes., Objective: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance., Patients: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied., Design: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines., Main Outcome Measures: MODY gene mutation screening and P379H mutant protein transactivation assay., Results: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H) of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter., Conclusions: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H) and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.

This was a prospective, longitudinal and descriptive study of 117 Mexican girls with Turner's syndrome (TS) followed from diagnosis to 18 years old. Height, weight and growth velocity were evaluated every 4-6 months, and bone age was assessed annually. Adult height was reached in 87 girls. All the girls were treated during 1 year with conjugated estrogens at bone age of 12 years, and subsequently with mixed estrogen/progestogen. Growth retardation in girls with TS is apparent at birth (2.7 +/- 0.9 kg and 46.3 +/- 5.0 cm) and in childhood, but becomes most marked when puberty would normally occur. Mean growth velocity was less than 25th percentile from birth to 2 years, less than 10th percentile between 3-9 years, and less than 3rd percentile from 10 to 18 years of age. Final adult height was 136.9 +/- 5.5 cm, but it is affected by the particular karyotype: 46,Xi(Xq): 134.5 cm, 45,XO: 137.3 cm, and 45XO/46,XX: 139 cm.

Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated Mexican patients and the corresponding mutant alleles in their parents by amplification of the functional CYP21 gene by PCR, followed by direct sequence analysis. The study included patients diagnosed with the three clinical forms of the disease. Our results revealed: (1) the presence of relatively few mutations or combinations of mutations associated with particular phenotypes; (2) the presence of putative new mutations; (3) the finding of identical genotypes in patients displaying discordant phenotypes; (4) the identification of patients lacking all previous reported mutations; and (5) an apparent high frequency of germ-line mutations. The absence of previously reported mutations in about 22% of the disease alleles, the finding of putative new mutations in some of the patients lacking previously known mutations, and the apparent high prevalence of germ-line mutations make evident the differences in the genetic background leading to this disorder between the Caucasian and the Mexican populations.

Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes, affecting 5% of the general population. Genetic factors play an important role in the development of the disease. While in other populations NIDDM is usually diagnosed after the fifth decade of life, in Mexico a large proportion of patients develop the disease at an early age (between the third and the fourth decade). In Caucasian population, mutations in the glucokinase gene, the TCF1, and TCF14 genes, have been identified in a subgroup of early-onset NIDDM patients denominated MODY (maturity-onset diabetes of the young), which show an autosomal dominant pattern of inheritance. As a first step in the molecular characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysis and/or direct sequencing in 26 individuals from 22 independent families, where at least four can be classified as MODY. No mutations were detected in the exons or the intron-exon boundaries of the gene in any of the screened individuals. The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci. Through computer simulation analysis we identified at least four informative families which will be used for further linkage studies.

Purpose: To investigate insulin serum concentrations in basal and stimulated conditions in a group of Mexican adolescents presenting menstrual disturbances., Methods: A total of 77 post-menarchial adolescents were studied: 65 with a chronological age of 15 +/- 1.7 years (mean +/- SD) had persistent anovulation and represented the study group; 12 were normal ovulatory adolescents (15 +/- 1.2 years) and served as controls. Body mass index (BMI), waist to hip ratio (W/H), presence and severity of acne, hirsutism, acanthosis nigricans (AN) and follicular hyperkeratosis were recorded. Transabdominal pelvic ultrasound was performed and LH, FSH, estradiol, prolactin, testosterone, androstenedione and sex hormone binding globulin (SHBG) concentrations were measured in plasma by specific immunoassays. Glucose and insulin levels were determined in venous blood following an overnight fasting and two hours after a standardized breakfast., Results: Anovulatory patients were divided in three groups depending on the presence of AN and overweight (BMI > 25). The insulin concentration in the study patients were remarkably higher than the values reported in the medical literature. Statistically significant differences were also found in fasting and postprandial insulin concentrations among the three anovulatory groups. Insulin values correlated with the severity of AN, W/H ratio, BMI and SHBG serum levels., Conclusions: Our study indicates that moderate to severe hyperinsulinemia is present in a high proportion of our adolescent anovulatory population. Whether hyperinsulinemia represents a transitory peripubertal event or is a predictive marker of chronic anovulation and metabolic derangement in adult life needs further investigation.

Steroid 21-hydroxylase deficiency is caused by mutations in the CYP21 gene. Approximately 95% of mutant alleles are generated by recombination events between the active gene CYP21 and its highly homologous pseudogene, CYP21P. Deletion alleles are generated by unequal crossing over, while point mutations are the result of gene conversion events. Deletions account for 20-25% of the 21-hydroxylase deficiency alleles in most populations studied. We have looked for deletions among 53 unrelated Mexican patients with steroid 21-hydroxylase deficiency and found that deletions represent less than 1% of the disease alleles. These findings suggest that nearly all mutant alleles in our patient population contain point mutations and that the low representation of deletion alleles among clinically diagnosed patients may be due to missing detection of salt wasters, mainly males, who may die during the neonatal period.

Ten growth hormone deficient patients (GHDP) (six girls & four boys) with chronological age range six-15 years old, received recombinant human growth hormone (GH) (0.6 UI/kg/week) in three subcutaneous injections per week over 14 months. A complete physical examination was performed monthly; thyroid hormones concentrations every two months, as well as, bone age every four months were determined. Growth velocity was higher in the first six months' treatment (12.73 +/- 1.65 cm/yr vs 10.6 +/- 1.67 cm/yr; previous growth velocity 3.76 +/- 2.4 cm/yr). The variables with better prognosis were: lower previous growth velocity, lower chronological age (< 12 ys), lower bone age (< 8 ys), higher BMI than ideal; and higher acid alkaline phosphate during treatment. Two of ours patients developed biochemical hypothyroidism during the treatment period, and they needed hormonal substitutive therapy. With GH treatment a harmonious growth is obtain with bone age progress according chronological age. The height of GHDP treated with GH do not approaches the height range of their parents, probably due the time of treatment. In the follow-up of all patients treated with GH is important to realize periodical laboratories screenings looking for another hypothalamic and/or hypophyseal deficiencies.