Familial hypercholesterolemia in Mexico: Initial insights from the national registry.

BACKGROUND: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. OBJECTIVE: Report the results of the first years (2017-2019) of the Mexican FH registry. METHODS: There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations. RESULTS: To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C <100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033). CONCLUSION: The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.

The development of the Mexican Familial Hypercholesterolemia (FH) National Registry.

BACKGROUND AND AIMS: In Mexico, familial hypercholesterolemia (FH) is, as in other parts of the world, largely underdiagnosed and undertreated, and represents a significant burden to the healthcare system. However, there is not enough information to design public policies against the disease. Genetic studies have shown that LDLR mutations are the most common cause, but in a large percentage of the cases, no mutation has been identified in the FH genes. METHODS: In accordance with the procedures of the European Atherosclerosis Society (EAS) FH registries network, the Mexican FH registry (www.fhmexico.org.mx) was launched in December 2017 to address the gaps in knowledge regarding this disease. Reference centres and the main nationwide public health providers have been invited to participate. RESULTS: To date, 142 cases have been registered. The mean age at diagnosis of probands is 36.42 ±â€¯19.9 years (adults and children). Tendon xanthomas or premature corneal arcus were present in 40% and 17.6%, respectively. Molecular analysis was present in 70%, with over 95% of alterations located on the LDL receptor gene. The median untreated LDL-C is 6.5 (5.6-8.4) mmol/l and the median on treatment LDL-C level is 4.3 ±â€¯1.7 mmol/l. CONCLUSIONS: The Mexican FH registry aims to obtain real world information regarding the management of patients in this country. By participating in this global call to action, we hope to improve both short and long term outcomes for all FH patients in Mexico.

Frecuencia, aspectos clínicos y moleculares de la hipercolesterolemia familiar en una unidad de endocrinología de Ciudad Bolívar, Venezuela / Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela

Objetivo: Describir la frecuencia, los aspectos clínicos, bioquímicos y moleculares de la hipercolesterolemia familiar (HF) en sujetos que acuden a una unidad de endocrinología. Métodos: Estudio observacional, descriptivo en el que se evaluaron 3.140 sujetos que fueron atendidos en la Unidad de Endocrinología del Centro Médico Orinoco en Ciudad Bolívar, Venezuela, desde el 7 de enero del 2013 al 9 de diciembre del 2016. Los casos índice fueron seleccionados de acuerdo con los criterios de la Red de Clínicas de Lípidos de Holanda. Se midieron lípidos plasmáticos. El análisis molecular se realizó por medio de secuenciación de ADN de los genes LDLR y APOB. Resultados: De los 3.140 sujetos evaluados, 10 (0,32%) tuvieron características clínicas y bioquímicas compatibles con HF. Todos, excepto uno, eran de sexo femenino. Tres pacientes tuvieron antecedente familiar en primer grado de enfermedad coronaria prematura y ninguno antecedente personal de esta patología. Tres pacientes tuvieron obesidad, 3 hipertensión arterial y ninguno tuvo diabetes. Tres pacientes presentaban xantomas tendinosos y solo uno arco corneal. Los valores de c-LDL oscilaron entre 191 y 486mg/dl. Solo 2 recibían tratamiento con estatinas. En 4 pacientes se identificó la causa genética de la HF: 3 de ellos por mutaciones en el gen LDLR y uno por mutación en el exón 26 del gen APOB. Conclusión: Aproximadamente una de cada 300 personas que acuden a consulta en esta unidad de endocrinología presentan HF. Las mutaciones en el gen LDLR son las principales causantes de HF en este grupo de pacientes (AU)

Objective: To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. Methods: An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. Results: Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. Conclusion: Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause (AU)

Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela. / Frecuencia, aspectos clínicos y moleculares de la hipercolesterolemia familiar en una unidad de endocrinología de Ciudad Bolívar, Venezuela.

OBJECTIVE: To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. METHODS: An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. RESULTS: Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. CONCLUSION: Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause.

The panorama of familial hypercholesterolemia in Latin America: a systematic review.

The burden caused by familial hypercholesterolemia (FH) varies among countries and ethnic groups. The prevalence and characteristics of FH in Latin American (LA) countries is largely unknown. We present a systematic review (following the PRISMA statement) of FH in LA countries. The epidemiology, genetics, screening, management, and unique challenges encountered in these countries are discussed. Published reports discussing FH in Hispanic or LA groups was considered for analysis. Thirty studies were included representing 10 countries. The bulk of the data was generated in Brazil and Mexico. Few countries have registries and there was little commonality in FH mutations between LA countries. LDL receptor mutations predominate; APOB and PCSK9 mutations are rare. No mutation was found in an FH gene in nearly 50% of cases. In addition, some country-specific mutations have been reported. Scant information exists regarding models of care, cascade screening, cost, treatment effectiveness, morbidity, and mortality. In conclusion, FH is largely underdiagnosed and undertreated in the LA region. The genetic admixture with indigenous populations, producing mestizo's groups, may influence the mutational findings in Latin America. Potential opportunities to close gaps in knowledge and health care are identified.

Familial whole-arm translocations (1;19), (9;13), and (12;21): a review of 101 constitutional exchanges.

We report here on 3 familial whole-arm translocations (WATs), namely the 8th instance of t(1;19)(p10;q10) and 2 novel exchanges: t(9;13)(p10;q10) and t(12;21)(p10;q10). The exchanges (1;19) and (12;21) were ascertained through a balanced carrier, whereas the t(9;13) was first diagnosed in a boy with a trisomy 9p syndrome and der(9p13p). Results of FISH analyses with the appropriate ?-satellite probes were as follows. Family 1, t(1;19): the D1Z5 probe gave a strong signal on both the normal chromosome 1 and the der(1q19p) as well as a weak signal on the der(1p19q). Family 2, t(9;13): the centromere-9 alphoid and D13Z1/D21Z1 probes under standard stringency gave no signal on the der(9p13p) in both the proband and a carrier brother, whereas the der(9q13q) was labelled only with the centromere-9 alphoid repeat in the latter; yet, this probe under low stringency revealed a residual amount of alphoid DNA on the der(9p13p) in the carrier. Family 3, t(12;21): the D12Z3 probe gave a signal on the normal chromosome 12 and the der(12p21q), whereas the D13Z1/D21Z1 repeat labelled the der(12q21p), the normal chromosome 21, and both chromosomes 13. Out of 101 WATs compiled here, 73 are distinct exchanges, including 32 instances between chromosomes with common alphoid repeats. Moreover, 7/9 of recurrent WATs involved chromosomes from the same alphoid family. Thus constitutional WATs appear to recur more frequently than other reciprocal exchanges, often involve chromosomes with common alphoid repeats, and can mostly be accounted for the great homology in alphoid DNA that favours mispairing and illegitimate nonhomologous recombination.

Prevalence of the BCR/ABL1 transcripts in Mexican patients with chronic myelogenous leukemia.

RT-PCR studies in 93 patients with chronic myelogenous leukemia from the Mexican West were done in order to know the proportion of b2a2 and b3a2 BCR/ABL1 transcripts. Forty-five patients showed the b3a2 transcript (48%), 37 (40%) displayed the b2a2 and in 11 cases (12%) both transcripts were detected. Statistical analyses showed that these figures are in accordance with two of three similar studies realized in Mexican population. Moreover, significant differences were found among Mexican people and patients from other countries, namely Ecuador, England, Italy, Poland, Japan, and Thailand. Ecuadorian patients showed differences with all the populations analyzed. These variations could be due to a different genetic background.