Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some clinical clues should alert paediatricians to the possibility of metabolic liver diseases. They can be classified into three categories: (i) Manifestations due to hepatocellular necrosis, acute or subacute, which can reveal galactosaemia, hereditary fructose intolerance, tyrosinaemia type I, Wilson disease and alpha 1-antitrypsin deficiency. Symptoms and signs suggestive of Reye syndrome should lead to a study of fatty acid oxidation and urea cycle enzymes. All these manifestations may necessitate a rapid diagnosis and treatment when liver dysfunction is severe. (ii) Cholestatic jaundice can reveal alpha 1-antitrypsin deficiency, Byler's disease, cystic fibrosis, Niemann-Pick disease and some disorders of peroxisome biogenesis. (iii) Hepatomegaly can reveal disorders with liver damage but also storage diseases such as glycogen storage diseases, cholesteryl ester storage disease and, when associated with splenomegaly, lysosomal storage diseases. Appropriate investigations for recognizing all these entities are proposed.
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PMID:Clinical presentation of metabolic liver disease. 174 17

We identified a partial gene deletion of ATP7B in a patient with Wilson disease with hepatic onset. The deletion covered exon 20 including major parts of the flanking introns. The breakpoints were identified and the size of the deletion determined to be 2144 bp. The deletion is predicted to lead to a mutated protein product containing 45 aberrant amino acids after transmembrane domain 7, and lacking the transmembrane domain 8 as well as the entire C-terminal cytoplasmic tail. This is the first time a partial gene deletion has been demonstrated in ATP7B. The patient presented at age 10 with hepatic manifestations, including severe jaundice, hepato-splenomegaly, ascites, and spider naevi. The liver biopsy showed fibrosis and early signs of cirrhosis. There was a Kayser-Fleischer ring but no neurological manifestations. All symptoms disappeared with penicillamine therapy. This suggests that the C-terminal cytoplasmatic tail of ATP7B, is not essential for its neurological function. Large deletions in ATP7B may be an overlooked cause of Wilson disease. Patients that are homozygotes for deletions may be valuable for the understanding of the function of various regions of the ATP7B protein.
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PMID:Homozygosity for a gross partial gene deletion of the C-terminal end of ATP7B in a Wilson patient with hepatic and no neurological manifestations. 1653 67

Background: Patients with Wilson disease (WD) progress to cirrhosis at an early age but have good prognoses. This study aimed to delineate hepatic features in WD patients with or without cirrhosis. Methods: Medical data were retrospectively collected from 27 July 2015 to 27 June 2018. WD patients were divided into two groups based on whether or not they progressed to cirrhosis. Liver function, portal hypertension features and hematocytopenia rates were compared between groups. Results: The study enrolled 119 WD patients with cirrhosis and 53 WD patients without cirrhosis. There were no differences between groups for liver enzyme levels or incidence rates of Kayser-Fleischer ring (all P > 0.05). Ascites and hepatic encephalopathy were nearly absent in both groups, and almost all patients were Child-Pugh group A. However, WD-associated cirrhotic patients had a higher prothrombin time (beta = 0.908, P = 0.004) and international normalized ratio (beta = 0.089, P = 0.040), wider portal vein diameter (beta = 1.330, P < 0.001), and an increased risk of splenomegaly/splenectomy (odds ratio [OR] = 4.36, 95% confidence interval [CI]: 2.15-8.84, P < 0.001). Moreover, WD-associated cirrhotic patients have significantly increased risks of leukopenia (OR = 2.30, 95% CI: 1.00-5.25, P = 0.049) and thrombocytopenia (OR = 6.89, 95% CI: 2.01-23.59, P = 0.002). Conclusions: Despite presenting good outcomes, mild hepatocyte injury, and good hepatic metabolic function, WD-associated cirrhotic patients show more serious impairment of hepatic synthetic function, wider portal vein diameter, and higher risk of splenomegaly due to portal hypertension.
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PMID:Cirrhosis in Wilson Disease is characterized by Impaired Hepatic Synthesis, Leukopenia and Thrombocytopenia. 3262 91