RESUMEN
Background: Hereditary tyrosinemia type 1 is a rare genetic disorder leading to liver cirrhosis and hepatocellular carcinoma. Few decades ago, dietary measures and ultimately liver transplant constituted the only treatment modalities. Nowadays, early diagnosis and therapy with nitisinone can reverse the clinical picture. In developing countries, diagnostic and therapeutic challenges may affect the outcome of this disease. The choice of the treatment modality may depend on the economic status of each country. Few reports on the long-term outcome of hereditary tyrosinemia type 1 are available from developing and Arab countries. Methods: A retrospective study of charts of Lebanese patients diagnosed with tyrosinemia type 1 and followed, at the American University of Beirut, during a 12-year period was performed. Clinical presentation and liver biochemical profile at diagnosis were analyzed, along with therapeutic modalities and long-term outcome. Results: Twenty-two children were diagnosed and followed during the study period. Median age at diagnosis was 7 months (range: one day to 35 months). Most of the patients presented with hepatomegaly and jaundice. Four patients were referred for atypical presentations with developmental delay and seizures, secondary to undiagnosed hypoglycemia episodes. Around half of the patients presented with failure to thrive. Transaminitis, cholestasis and increased α-fetoprotein level were variably present at diagnosis (36% to 50%). All patients had elevated plasma tyrosine and urinary succinylacetone levels. Genetic testing was performed in 9%. Only one third could be treated with nitisinone. Liver transplant was electively performed in 9% of cases, to overcome the long-term cost of nitisinone. One third of the patients died between the age of 1 month and 11 years. Surviving patients are still candidates for liver transplant. Conclusion: Our experience reflects the challenges of diagnosis and treatment of hereditary tyrosinemia type 1 in a developing country. In the absence of specific neonatal screening, early diagnosis relies mostly on the clinical awareness of the physician. Long-term nitisinone use may be deterred by its high cost and liver transplantation carries risks of surgical complications. New, effective, and less expensive treatments are needed, especially for developing countries.
RESUMEN
Patients and Methods: A retrospective chart review of 32 GSD- I patients, followed at the American University of Beirut Medical Center, between 2007 and 2018 was conducted. Diagnosis was confirmed by enzymatic and/or genetic studies. Clinical presentation, growth, and kidney outcome were assessed. All patients were evaluated for body mass index, blood parameters of metabolic control including uric acid, alanine, lactic acid, and triglycerides in blood. Kidney evaluation included creatinine clearance, microalbuminuria, citraturia, and calciuria as well as urine microalbumin/creatinine ratio. Results: Almost one third of GSD-I patients developed microalbuminuria. This was detected below 7 months of age in 36% of patients who required early treatment with ACEI with significant reduction in albuminuria. Kidney stones were present in 6% and were associated with hypercalciuria and hypocitraturia. Poor metabolic control reflected by hyperuricemia, lactic acidosis, and hyperalaninemia were noted only in patients who developed microalbuminuria. Conclusion: Glomerular injury may appear in early infancy in poorly controlled patients. Adequate metabolic control and ACEI therapy may improve kidney outcome in GSD I patients. Plasma alanine appears to be a promising and reliable marker reflecting metabolic control in GSD-I patients.
RESUMEN
BACKGROUND: The burden of zinc deficiency on children includes an increased incidence of diarrhea, failure to thrive (FTT) and short stature. The aim of this study was to assess whether children with FTT and/or short stature have lower dietary zinc intake and plasma zinc concentrations compared to controls. METHODS: A case-control study conducted at the American University of Beirut Medical Center included 161 subjects from 1 to 10 years of age. RESULTS: Cases had a statistically significant lower energy intake (960.9 vs. 1,135.2 kcal for controls, p = 0.010), lower level of fat (30.3 vs. 36.5 g/day, p = 0.0043) and iron intake (7.4 vs. 9.1 mg/day, p = 0.034). There was no difference in zinc, copper, carbohydrate and protein intake between the 2 groups. The plasma zinc concentration did not differ between the cases and controls (97.4 vs. 98.2 µg/dl, p = 0.882). More cases had mild-to-moderate zinc deficiency when compared to controls with 10.3 vs. 3.6%, p = 0.095. CONCLUSION: Our study did not show statistically significant difference in dietary zinc intake and plasma zinc concentrations between children with FTT and/or short stature compared to healthy controls. A prospective study is planned to assess the effect of zinc supplementation on growth parameters in FTT children.