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)

Glucosidase I is an important enzyme in N-linked glycoprotein processing, removing specifically distal alpha-1,2-linked glucose from the Glc3Man9GlcNAc2 precursor after its en bloc transfer from dolichyl diphosphate to a nascent polypeptide chain in the endoplasmic reticulum. We have identified a glucosidase I defect in a neonate with severe generalized hypotonia and dysmorphic features. The clinical course was progressive and was characterized by the occurrence of hepatomegaly, hypoventilation, feeding problems, seizures, and fatal outcome at age 74 d. The accumulation of the tetrasaccharide Glc(alpha1-2)Glc(alpha1-3)Glc(alpha1-3)Man in the patient's urine indicated a glycosylation disorder. Enzymological studies on liver tissue and cultured skin fibroblasts revealed a severe glucosidase I deficiency. The residual activity was <3% of that of controls. Glucosidase I activities in cultured skin fibroblasts from both parents were found to be 50% of those of controls. Tissues from the patient subjected to SDS-PAGE followed by immunoblotting revealed strongly decreased amounts of glucosidase I protein in the homogenate of the liver, and a less-severe decrease in cultured skin fibroblasts. Molecular studies showed that the patient was a compound heterozygote for two missense mutations in the glucosidase I gene: (1) one allele harbored a G-->C transition at nucleotide (nt) 1587, resulting in the substitution of Arg at position 486 by Thr (R486T), and (2) on the other allele a T-->C transition at nt 2085 resulted in the substitution of Phe at position 652 by Leu (F652L). The mother was heterozygous for the G-->C transition, whereas the father was heterozygous for the T-->C transition. These base changes were not seen in 100 control DNA samples. A causal relationship between the alpha-glucosidase I deficiency and the disease is postulated.
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PMID:A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency. 1078 35

Hereditary fructose intolerance (HFI) is an autosomal recessive disease caused by catalytic deficiency of aldolase B (fructose-1, 6-bisphosphate aldolase). Herein we report on a case of hereditary fructose intolerance with initial presentation of episodic unconsciousness, seizure, hypoglycemia, hepatomegaly, and abnormal liver function since the patient was 11 months old. She was diagnosed as Reye's-like syndrome according to a liver biopsy done at 20 months of age. As she grew up, cold sweating, abdominal pain or gastrointestinal discomfort shortly after the intake of fruits was noted and she developed an aversion to fruits, vegetables and sweet-tasting foods. At 9 years of age, a fructose tolerance test signified a positive result that induced hypoglycemia, transient hypophosphatemia, hyperuricaemia, elevation of serum magnesium, and accumulation of lactic acid. Appropriate dietary management and precautions were recommended. The patient has been symptom-free and exhibited normal growth and development when followed up to 12 years of age.
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PMID:Hereditary fructose intolerance presenting as Reye's-like syndrome: report of one case. 1102 Oct 9

When possible, diseases by expectant mothers and newborns, like long-term disabilities also, should be prevented by establishing early diagnoses, evaluation and implementation adequate therapy. The major goal of medical care is prevention of disorders with provision of adequate prenatal care for the expectant mother and precautions regarding the exposure to teratogenic infections. The range of pathological conditions produced by infections agents is wide, and the difference between maternal and fetal effects caused by any one agent is also important. Some maternal infections, especially during the early gestation, can result in fetal loss or malformation because the ability of the fetus to resist infectious organisms is limited and the fetal immunologic system is unable to prevent the disemination of infectious organisms to the various tissues. These infections are responsible for significant congenital neonatal morbidity as for as compromises a child's quality of life and infertility and sterility. One group of microbial agents--generally known as TORCH infections can cause remarkably similar manifestations, and is uncommon to test all when a prenatal infection is suspected. We analysed the practice of TORCH analyses with our patients and their mothers during last year (1999th) at the Pediatric Clinic and Clinic of Gynecology and Obstetrition-UCC Tuzla. At this time there were 5.028 deliveries. Out of short figure 544 or 10.8% newborns were early born and 245 or 4.8% were hypotrophic and 62 were still-born or 12.3 from 1000 deliveries. TORCH infection was analysed only in few cases. In the same period there were 3.457 children treated at the Pediatric Clinic in Tuzla. Only in 20 cases or 0.58% TORCH was made. Three or 15% were with remarkable sequeles like microcephaly, cerebrospinal liquid abnormality, seizures, hepatomegaly, cirrosis etc. TORCH analysis was made with all mothers. Only one was serologic CMV positive and we started with the therapy. History of four mothers or 20% have data about spontaneous abortions, and in other four or 20% we found data about early deliveries. The prevention of conatal infections was not made by any one. In our small group we made TORCH because of evident problems that were suspected of conatal infections. We concluded that there is a big risk of untreated maternal infections with women in fertile age in Bosnia and Herzegovina. This problem is not enough present in our medical practice.
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PMID:[TORCH infections in mothers as a cause of neonatal morbidity]. 1121 2

Intracranial calcification and microcephaly, which represent the main clinical features of the TORCH-syndrome, can also be determined by a rare autosomal recessive infection-like condition named pseudo-TORCH syndrome. This emerging entity has been registered in eight families so far. We report on five patients from three unrelated Italian families affected by pseudo-TORCH syndrome. Reevaluation of literature allowed us to draw a specific clinical profile of the syndrome. Indeed, congenital microcephaly, congenital cerebral calcification, spasticity and seizures are the main clinical features, and have been present in almost all patients reported so far. On the contrary, findings resembling congenital infectious diseases including neonatal icterus, hyperbilirubinemia, thrombocytopenia, and hepatomegaly, affect less than half of the patients. Considering the diagnosis of pseudo-TORCH syndrome in patients with neonatal microcephaly and cerebral calcification is necessary since an early diagnosis may allow adequate genetic counseling to the families.
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PMID:Pseudo-TORCH syndrome or Baraitser-Reardon syndrome: diagnostic criteria. 1122 24

Medium chain acyl-CoA dehydrogenase (MCAD) is a tetrameric flavoprotein essential for the beta-oxidation of medium chain fatty acids. MCAD deficiency (MCADD) is an inherited error of fatty acid metabolism. The gene for MCAD is located on chromosome one (1p31). One variant of the MCAD gene, G985A, a point mutation causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD protein, has been found in 90% of the alleles in MCADD patients identified retrospectively. There is a high frequency of MCADD among people of Northern European descent, which is believed to be due to a founder effect. MCADD is inherited in an autosomal recessive manner. Of patients clinically diagnosed with MCADD, 81% who have been identified retrospectively are homozygous for K304E, and 18% are compound heterozygotes for K304E. Clinical data on the probability of clinical disease indicates that MCADD patients are at risk for the following outcomes: hypoglycemia, vomiting, lethargy, encephalopathy, respiratory arrest, hepatomegaly, seizures, apnea, cardiac arrest, coma, and sudden and unexpected death. Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). Differences in clinical disease specific to allelic variants have not been documented. Factors that may increase risk for disease onset or modify disease severity are age when the first episode occurred, fasting, and presence of infection. Acute attacks must be treated immediately with appropriate intravenous doses of glucose. For those diagnosed, long-term management of the disease includes preventing stress caused by fasting and maintaining a high-carbohydrate, reduced-fat diet, and carnitine supplementation. Hospitalization costs attributable to morbidity and mortality from MCADD are unknown; MCADD is not a diagnosis in the International Classification of Disease, 10th Revision (ICD-10) codebook. Furthermore, the penetrance of the MCAD genotypes is unknown; there appears to be a substantial number of asymptomatic MCADD individuals and some uncertainty regarding which individuals will manifest symptoms and which individuals will remain asymptomatic. Several technologies are available to detect MCADD. Diagnostic technologies include DNA-based tests for K304E mutations using the polymerase chain reaction (PCR), and the detection of abnormal metabolites in urine. Screening technologies include tandem mass spectrometry (MS/MS), which detects abnormal metabolites mostly in blood. State programs are beginning to offer screening in newborns for MCADD using MS/MS. In addition, a private company currently offers voluntary supplemental newborn screening for MCADD to birthing centers.
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PMID:Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review. 1126 45

Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic' and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, while the other isoform occurs in skeletal muscle and is the predominant form in heart. Reported patients with CPT I deficiency lack activity of the hepatic isoform and present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with raised transaminases, seizures and coma. We discuss four new cases in three families showing, variously, renal tubular acidosis, transient hyperlipidaemia and, paradoxically, myopathy with elevated creatinine kinase or cardiac involvement in the neonatal period as additional features that deserve wider recognition.
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PMID:Features of carnitine palmitoyltransferase type I deficiency. 1128 80

The case of a 66-year-old patient is reported in view of the rarity of his condition: a case of subacute encephalopathy with seizures in alcoholics (SESA syndrome), described first in 1981 by Niedermeyer, et al. Wernicke-type aphasia, epileptic seizures (generalized tonic-clonic) and PLEDs EEG pattern dominated the neurological picture, in addition to hepatomegaly and rhabdomyolysis. This condition differs from all other known CNS complications in chronic alcoholism and is withdrawal-independent. It is prognostically favorable as far as the syndrome as such is concerned.
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PMID:Subacute encephalopathy with epileptic seizures in alcoholism (SESA): case report. 1168 11

To determine the magnitude of the problem posed by primary dengue infection in children and the distinctive clinical clues that may differ from those with secondary infection, 996 children serologically diagnosed with dengue infection and admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand between 1988 and 1995 were retrospectively reviewed. One hundred and thirty-nine cases (14.0%) were serologically proved to be primary dengue infection. Of these, 72 were males and 67 were females, with a mean age of 4.8 years. Common manifestations by order of frequency included fever (97.8%), hepatomegaly (71.9%), vomiting (59.0%), decreased appetite (55.4%), coryza (52.5%), drowsiness (39.6%), diarrhea (34.5%), rash (33.8%), abdominal pain (23.0%) and seizure (15.8%). The mean duration of fever before admission was 4.6 days. Common sites of bleeding were skin (41.7%), mucous membrane (14.4%) and the gastrointestinal tract (12.2%). Clinical diagnosis was categorized into dengue fever (22.3%), dengue hemorrhagic fever (60.4%) and dengue shock syndrome (17.3%). Three patients (2.2%) died. Compared with the children with secondary dengue infection (n=139), children with primary dengue infections tended to be younger, presented more commonly with coryza, diarrhea, rash and seizure; and less commonly with vomiting, headache and abdominal pain (p < 0.05). The maximal hematocrit level, the mean difference between maximal and minimal hematocrit values and the maximal percentage of neutrophils were significantly lower in the study group, whereas the maximal percentage of lymphocytes was significantly higher. Dengue fever was more common and dengue shock syndrome was less common in the study group (p < 0.05). This study has emphasized that primary dengue infection is not uncommon and is less severe than secondary infection. Clinical presentations and laboratory findings are somewhat different between the two conditions.
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PMID:Primary dengue infection: what are the clinical distinctions from secondary infection? 1194 2

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

Case records of HIV infected patients were analyzed for identifying neurological manifestations. Eight patients (7 males) were identified to have probable HIV encephalopathy (in a period of 24 months) as per the CDC revised classification system. Their ages ranged from one year to ten years. The neurological manifestations noted included-developmental delay (2 cases), seizures (6 cases), acute onset alteration of sensorium (4 cases), aphasia (2 cases), loss of vision (2 cases), focal neurological deficits (6 cases), brisk deep tendon reflexes (7 cases), extensor plantar responses (5 cases) and signs of cerebellar dysfunction (2 cases). Other clinical features included growth failure, microcephaly, fever, lymphadenopathy, hepatomegaly, splenomegaly, pneumonia, otorrhea and oral candidiasis. Cerebrospinal fluid studies were normal. The neuroimaging features included cerebral atrophy and ventricular dilatation, cerebral infarction, basal ganglia calcification and cerebellar atrophy. Childhood HIV infection may have a variety of neurological abnormalities. HIV infection should be suspected in children presenting with unexplained neurological manifestations and growth failure.
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PMID:Neurological manifestations of HIV infection. 1265 56


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