Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 4-month-old boy, with late-onset argininosuccinate lyase (ASL) deficiency with hepatomegaly, was treated by protein restricted diet and arginine supplementation; he was followed for 3 years. Hepatomegaly and mild liver dysfunction persisted without significant hyperammonemia. He maintained normal psychomotor development to the age of 12 months, but, at 3 years of age, his developmental status is in the borderline normal range. Liver biopsy performed at 12 months of age demonstrated swollen and pale hepatocytes with abnormal glycogen deposition and mild periportal fibrosis. A subsequent liver biopsy at 3 years of age showed progressive liver fibrosis in the periportal and central areas, which extended into the liver lobule. These findings suggest that liver impairment in ASL deficiency may advance without significant hyperammonemia and underline the importance of repeated liver biopsy in this disorder, even when the plasma ammonia level is well controlled.
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PMID:Progressive liver fibrosis in late-onset argininosuccinate lyase deficiency. 1237 Jul 74

Urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino acids or their nitrogen-free analogues has increased survival. The authors report 5 cases of urea cycle disorders, all of whom developed and were rescued from hyperammonemic coma. However, the eventual outcome was quite variable. Argininosuccinate lyase deficiency (ALD) Case 1. A 2 month old male infant, a product of a consanguineous marriage (Suphanburi province); developed poor feeding on day 7, lethargy, convulsion, hepatomegaly and respiratory alkalosis leading to respiratory failure and coma. Hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD. He is now 9 years old and severely retarded. Case 2. A male infant with history of lethargy, poor feeding on day 3, treated as sepsis and required respiratory support for 6 days; subsequently readmitted at age 2 weeks with vomitting, lethargy, seizure activity and hyperammonemia, and was treated by a local pediatrician in Songkhla province. There was a history of parental consanguinity and he was referred to Siriraj Hospital on day 64 with severe essential amino acid deficiency and acrodermatitis enteropathica with markedly elevated plasma citrulline level. In spite of aggressive treatment; the patient developed sepsis and he expired on day 78. Ornithine transcarbamylase deficiency (OTC) Case 3. An eleven-month-old male infant, the product of a non-consanguineous marriage, developed neonatal onset of hyperammonemia on day 5 after poor feeding, lethargy, hypothermia, seizure, apnea and coma. He was rescued from neonatal hyperammonemic coma on day 9 after aggressive treatment, but expired at eleven months of age after overwhelming sepsis. Case 4. A male infant, sibling of case 3 was referred to Siriraj Hospital on day 8 with hyperammonemia and coma. In spite of intensive genetic counseling given after the birth of their first child with OTC, the couple chose to have another baby without informing any physician. The baby developed vomiting and lethargy on day 2; subsequently hyperammonemia was noted. In spite of aggressive treatment given; hepatic dysfunction, renal failure and disseminated intravascular coagulation defects occurred on day 15. He expired on day 18 after parental permission for discontinuation of all treatment. Argininosuccinate synthetase deficiency (ASS) or Citrullinemia. Case 5. A seven week old female infant, the product of a consanguineous marriage and of Pakistani ethnic origin; developed intermittent vomiting from day 6. Initial diagnoses included ruminations, sepsis and pyloric stenosis for which she was operated on (day 30); however, vomiting continued; subsequently seizures, hyperammonemic coma developed and she was rescued from hyperammonemic coma within 30 hours. Significant elevations of citrulline and L-glutamine were demonstrated. She was discharged in excellent condition to her home in Dubai, the United Arab Emirates.
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PMID:Urea cycle disorders in Thai infants: a report of 5 cases. 1240 52

Argininosuccinicaciduria is a rare metabolic disorder of the urea cycle associated with the inability to excrete nitrogenous waste in the form of urea. Along with low serum arginine, hepatomegaly, and mental retardation, congenital trichorrhexis nodosa is a distinguishing feature of the disorder. We present a 3.5-year-old girl diagnosed with argininosuccinicaciduria who presented to the dermatology clinic with hair thinning and loss since birth. Microscopic evaluation revealed nodular swellings on the hair shafts and frayed cortical fibers consistent with the diagnosis of trichorrhexis nodosa occurring in the setting of argininosuccinicaciduria.
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PMID:Trichorrhexis nodosa secondary to argininosuccinicaciduria. 1730 Jun 44

Argininosuccinic aciduria (ASAuria) is an inborn error of metabolism caused by mutations in the argininosuccinate lyase (ASL) gene, which leads to the accumulation of argininosuccinic acid (ASA) in body fluids and severe hyperammonemia. A severe neonatal form and a milder late-onset variant are described. We report a novel ASL pseudogene located in the centromeric region of chromosome 7, 14 novel mutations in the ASL gene, and a novel intronic polymorphism found in a cohort of Italian patients. Our approach relied exclusively on genomic DNA analysis. We found seven missense mutations, two nonsense, three small insertions/deletions, and two splicing mutations. Only two patients harbored previously described mutations, and among the novel variants only two were present in more than one kindred. The pathogenicity of the splicing mutations was demonstrated by a functional splicing assay that employed a hybrid minigene. We also performed molecular modeling using the reported three-dimensional structure of ASL to predict the functional consequences of the missense mutations. There was no genotype-phenotype correlation. Patients with neonatal onset display developmental delay and seizures despite adequate metabolic control. Moreover, hepatomegaly, fibrosis, and abnormal liver function tests are common complications in these patients, but not in patients with the late infancy form. We stress the importance of mutation analysis in patients with ASAuria, to confirm the clinical diagnosis, and to perform DNA-based prenatal diagnosis in future pregnancies of these families.
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PMID:Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene. 1732 97

Argininosuccinate lyase deficiency is a urea cycle disorder which can present in the neonatal period with hyperammonemic encephalopathy, or later in childhood with episodic vomiting, growth and developmental delay. Abnormal hair, hepatomegaly, and hepatic fibrosis are unique features of this disorder. Twelve patients with argininosuccinate lyase deficiency were ascertained between 4 and 6 weeks of age by urine amino acid screening. One infant in a previously identified family was diagnosed shortly after birth. Diagnosis was confirmed by enzyme assay in red blood cells and/or skin fibroblasts. At the time of last follow-up, patients had been followed for 13-33 years. All patients were asymptomatic at detection, 7 had slightly increased blood ammonia, and all were initially treated with low-protein diet. Utilization of (14)C-citrulline by intact skin fibroblasts measured by (14)C incorporation into macromolecules was 74-135% of the control mean for 7 of the 8 patients studied. Nine patients had normal development, 4 had learning disability, 6 had EEG abnormalities, 3 had seizure disorder. None had any episodes of hyperammonemic coma. None had hepatomegaly. Patients detected by screening had higher enzyme activity measured by the (14)C-citrulline incorporation assay than comparison groups of patients with neonatal-onset and with late-onset detected by clinical disease. The ability to utilize (14)C-citrulline by intact fibroblasts seems to correlate with clinical outcome and may have prognostic value. It is likely that early diagnosis and treatment contributed to the relatively mild clinical course of the study group.
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PMID:Argininosuccinate lyase deficiency: longterm outcome of 13 patients detected by newborn screening. 1963 76