Diagnostic challenges of aminoacidopathies and organic acidemias in a developing country: a twelve-year experience.

BACKGROUND: Diagnosis of aminoacidopathies and organic acidemias constitutes a real challenge in a developing country with high consanguinity rate and no systematic newborn screening. We report a twelve-year experience with the identification of these disorders in Lebanon, based on their clinical and biochemical profiles. METHODS: In this retrospective study, we reviewed clinical presentation and biochemical investigations of 294 patients. Traditional chromatographic methods were used for analyses. Findings were linked to the identified disorders. RESULTS: Out of 2921 patients, presenting to our metabolic program with neurological, digestive, family history and/or other symptoms suggestive of aminoacidopathy or organic acidemia, 294 patients were included with confirmed amino or organic acid disorder. The overall analytical yield was 10%. Aminoacidopathies were three-fold higher than organic acidemias. Phenylketonuria and methylmalonic acidemia were the most frequent. The majority of patients (79%) were symptomatic (median age: 14months, range: 1day-44years), mainly with neurological manifestations (87%). Intellectual disability was mostly due to phenylketonuria (73%). Chronic liver failure was frequent in maple syrup urine disease (53%). Plasma amino and urine organic acid chromatography were diagnostic in 8.8% and 3.9% of analyzed cases, respectively. Change in chromatographic technique from reversed-phase to ion-exchange enhanced the detection of many aminoacidopathies. CONCLUSIONS: In the absence of newborn screening, the majority of aminoacidopathy and organic acidemia cases are still diagnosed clinically. This study emphasizes the importance of clinical awareness and accurate biochemical analyses as key tools for diagnosis in countries like ours, and the necessity for a comprehensive national newborn screening program.

Obesity is associated with insulin resistance and components of the metabolic syndrome in Lebanese adolescents.

BACKGROUND: Prevalence of metabolic syndrome (MS) in obese adolescents has been reported to range between 18-42%, depending on country of origin, thus suggesting an ethnic-based association between obesity and MS. AIM: This study aims to investigate the magnitude of the association between obesity, insulin resistance and components of MS among adolescents in Lebanon. SUBJECTS AND METHODS: The sample included 263 adolescents at 4(th) and 5(th) Tanner stages of puberty (104 obese; 78 overweight; 81 normal weight). Anthropometric, biochemical and blood pressure measurements were performed. Body fat was assessed using dual-energy X-ray absorptiometry. RESULTS: According to International Diabetes Federation criteria, MS was identified in 21.2% of obese, 3.8% of overweight and 1.2% of normal weight subjects. The most common metabolic abnormalities among subjects having MS were elevated waist circumference (96.2%), low HDL (96.2%) and hypertriglyceridemia (73.1%). Insulin resistance was identified in all subjects having MS. Regression analyses showed that percentage body fat, waist circumference and BMI were similar in their ability to predict the MS in this age group. CONCLUSIONS: MS was identified in a substantial proportion of Lebanese obese adolescents, thus highlighting the importance of early screening for obesity-associated metabolic abnormalities and of developing successful multi-component interventions addressing adolescent obesity.

Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people.

The authors assessed the impact of CYP2C9*2, CYP2C9*3, and/or VKORC1-1639G>A/1173C>T single-nucleotide polymorphisms on oral anticoagulants in a Lebanese population. This study recruited 231 Lebanese participants on long-term warfarin or acenocoumarol maintenance therapy with an international normalized ratio (INR) monitored at the American University of Beirut Medical Center. CYP2C9 and VKORC1 variant alleles were screened by real-time PCR. Plasma R- and S-warfarin and R- and S-acenocoumarol levels were assayed using high-performance liquid chromatography. The variant allele frequencies of CYP2C9*2, CYP2C9*3, and VKORC1 -1639G>A/1173C>T were 15.4%, 7.8%, and 52.4%, respectively. Fifty-five participants were excluded from analysis because of nontherapeutic INR values at recruitment, leaving 43 participants taking warfarin and 133 taking acenocoumarol. There was a significant decrease in the weekly maintenance dose of both drugs with CYP2C9 and VKORC1 variants when compared with wild-type patients. CYP2C9*2 had the least impact on the response to both drugs. The concentrations of R- and S-warfarin in plasma were significantly correlated with CYP2C9 genotypes. For acenocoumarol, time to reach target INR was more prolonged in patients carrying any CYP2C9 variant allele but failed to reach statistical significance because of low numbers of patients. There was no association between allelic variants and bleeding events. This is the first pharmacogenetic study of oral anticoagulants in Arabs. The authors showed that both CYP2C9 and VKORC1 polymorphisms are common in Lebanon and influence warfarin and acenocoumarol dose requirements, with the CYP2C9*2 polymorphism having less effect on acenocoumarol, the most commonly used oral anticoagulant in Lebanon.