The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitocho...The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liverdamage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.展开更多
The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders(UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant...The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders(UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant(OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.展开更多
Background:To observe the development of neonatal sleep among healthy infants of different conceptional age(CA)by analyzing the amplitude-integrated electroencephalography(aEEG)of their sleep-wake cycles(SWC).Methods:...Background:To observe the development of neonatal sleep among healthy infants of different conceptional age(CA)by analyzing the amplitude-integrated electroencephalography(aEEG)of their sleep-wake cycles(SWC).Methods:Bedside aEEG monitoring was carried out for healthy newborns from 32 to 46 weeks CA between September 1,2011 and August 30,2012.For each aEEG tracing,mean duration of every complete SWC,number of SWC repetition within 12 hours,mean duration of each narrow and broadband of SWC,mean voltage of the upper edge and lower edge of SWC,mean bandwidth of SWC were counted and calculated.Analysis of the correlations between voltages or bandwidth of SWC and CA was performed to assess the developmental changes of central nervous system of newborns with different CA.Results:The SWC of different CA on aEEG showed clearly identifiable trend after 32 weeks of CA.The occurrence of SWC gradually increases from preterm to post-term infants;term infants had longer SWC duration.The voltage of upper edge of the broadband decreased at 39 weeks,while the lower edge voltage increases and the bandwidth of broadband declined along with the growing CA.The upper edge of the narrowband dropped while the lower edge rised gradually,especially in preterm stage.The width of the narrowband narrowed down while CA increased.Conclusions:The SWC on aEEG of 32-46 weeks infants showed a continuous,dynamic and developmental progress.The appearance of SWC and the narrowing bandwidth of narrowband is the main indicator to identify the CA-dependent SWC from the preterm to the late preterm period.The lower edge of the broadband identifi es the term to post-term period.展开更多
Background: Methylmalonic aciduria (MMA) is a genetic disorder of aminoacid metabolism, due to mutations in methylmalonyl-CoA mutase, which leads to the accumulation of methylmalonic acid in body fluids. Patients typi...Background: Methylmalonic aciduria (MMA) is a genetic disorder of aminoacid metabolism, due to mutations in methylmalonyl-CoA mutase, which leads to the accumulation of methylmalonic acid in body fluids. Patients typically present at the age of 1 month to 1 year with dehydration, renal impairment as well as neurologic manifestations viz. seizure, encephalopathy, strokes and disease in the globus pallidi. The case: a 26-year-old man presented with severe acute on top of chronic renal disease with serum creatinine at 590 umol/L and bilateral 8 cm kidneys with thin and echogenic cortex. He had: (a) hypernatremic dehydration, metabolic acidosis and high ammonia level with (b) a history of multiple similar attacks since the age of 8 months. Diagnosis of MMA was confirmed by high serum and urine enzymatic levels as well as genetic testing. His initial management included support with replacements of fluids, electrolytes, and bicarbonates as well as intravenous dextrose, vitamin B12 and broad-spectrum antibiotic (Meropenem) for his chest infection. Subsequently, he received 1) CARBAGLU (carglumic acid) for 7 days to lower his ammonia level to Conclusion: Untreated homozygous MMA variants, can achieve adulthood with significant renal disease yet their morbidity and mortality can be ameliorated with diet and specific therapy.展开更多
文摘The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liverdamage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.
文摘The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders(UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant(OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.
基金This work was supported by the Guangzhou Science Technology and Innovation Commission 1563000668(Lian Zhang).
文摘Background:To observe the development of neonatal sleep among healthy infants of different conceptional age(CA)by analyzing the amplitude-integrated electroencephalography(aEEG)of their sleep-wake cycles(SWC).Methods:Bedside aEEG monitoring was carried out for healthy newborns from 32 to 46 weeks CA between September 1,2011 and August 30,2012.For each aEEG tracing,mean duration of every complete SWC,number of SWC repetition within 12 hours,mean duration of each narrow and broadband of SWC,mean voltage of the upper edge and lower edge of SWC,mean bandwidth of SWC were counted and calculated.Analysis of the correlations between voltages or bandwidth of SWC and CA was performed to assess the developmental changes of central nervous system of newborns with different CA.Results:The SWC of different CA on aEEG showed clearly identifiable trend after 32 weeks of CA.The occurrence of SWC gradually increases from preterm to post-term infants;term infants had longer SWC duration.The voltage of upper edge of the broadband decreased at 39 weeks,while the lower edge voltage increases and the bandwidth of broadband declined along with the growing CA.The upper edge of the narrowband dropped while the lower edge rised gradually,especially in preterm stage.The width of the narrowband narrowed down while CA increased.Conclusions:The SWC on aEEG of 32-46 weeks infants showed a continuous,dynamic and developmental progress.The appearance of SWC and the narrowing bandwidth of narrowband is the main indicator to identify the CA-dependent SWC from the preterm to the late preterm period.The lower edge of the broadband identifi es the term to post-term period.
文摘Background: Methylmalonic aciduria (MMA) is a genetic disorder of aminoacid metabolism, due to mutations in methylmalonyl-CoA mutase, which leads to the accumulation of methylmalonic acid in body fluids. Patients typically present at the age of 1 month to 1 year with dehydration, renal impairment as well as neurologic manifestations viz. seizure, encephalopathy, strokes and disease in the globus pallidi. The case: a 26-year-old man presented with severe acute on top of chronic renal disease with serum creatinine at 590 umol/L and bilateral 8 cm kidneys with thin and echogenic cortex. He had: (a) hypernatremic dehydration, metabolic acidosis and high ammonia level with (b) a history of multiple similar attacks since the age of 8 months. Diagnosis of MMA was confirmed by high serum and urine enzymatic levels as well as genetic testing. His initial management included support with replacements of fluids, electrolytes, and bicarbonates as well as intravenous dextrose, vitamin B12 and broad-spectrum antibiotic (Meropenem) for his chest infection. Subsequently, he received 1) CARBAGLU (carglumic acid) for 7 days to lower his ammonia level to Conclusion: Untreated homozygous MMA variants, can achieve adulthood with significant renal disease yet their morbidity and mortality can be ameliorated with diet and specific therapy.
