Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a 10 month old boy with alpha-mannosidosis who presented with recurrent bronchopneumonia and diarrhea. Facial coarsening, deafness, hepatosplenomegaly, umbilical hernia, pectus carinatum and widespread Mongolian spots were distinguishing features. He also had mild skeletal deformities grouped together as 'dysostosis multiplex', and vacuolated lymphocytes on peripheral blood smear. These findings coupled with an abnormal urinary oligosaccharide pattern led to the suspicion of a lysosomal storage disease in the patient which proved to be alpha-mannosidosis. An exceptionally low level of alpha-mannosidase activity was subsequently found in serum and cultured skin fibroblasts. The patient's brother, who had died at the age of 10 months, had similar features. To the best of our knowledge, this is the first case reported from Turkey.
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PMID:Alpha-mannosidosis: the first Turkish case. 779 63

Over a 10-year period, 28 Arab children with autosomal recessive osteopetrosis were seen in two hospitals in Riyadh, Saudi Arabia. Eighteen (64%) had osteopetrosis associated with metabolic acidosis probably due to a renal tubular defect; nine (32%) had a malignant infantile form of osteopetrosis and one had a mild form with delayed onset. Parental consanguinity was 56% and 40% among patients with and without acidosis respectively. Somatic and psychomotor retardation and recurrent bone fractures were common in both groups. Dental caries, cerebral calcification and optic atrophy were more frequent in patients with acidosis, while anaemia, hepatosplenomegaly and deafness were more common in patients without acidosis. To guarantee optimal rehabilitation, children with this progressive disease require an early multiteam approach.
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PMID:Osteopetrosis in children. 953 61

Autosomal recessive osteopetrosis is a rare congenital disorder characterized by the development of abnormally dense bones, acrocephaly, severe anemia, hepatosplenomegaly and progressive deafness and blindness. The clinical course is rapidly progressive and is lethal at a very young age in the absence of a bone marrow transplant. The failure to remodel developing bone that is the basis of the disease process is most likely due to a dysfunction of the bone resorptive cell, the osteoclast. This phenotype is similar to that of the murine mutation osteosclerosis (oc), which is localized to proximal mouse chromosome 19. Given the similarity between the human and murine phenotypes, we tested whether human osteopetrosis maps to a region of conserved synteny. Microsatellite markers in the region of 11q12-13 were found to be linked to osteopetrosis in two consanguineous Bedouin kindreds. Recombination events were used to define the disease interval to an approximately 14 cM region between D11S1983 and D11S2371. A maximum LOD score of 7. 94 was obtained with D11S449 at straight theta = 0.
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PMID:Human autosomal recessive osteopetrosis maps to 11q13, a position predicted by comparative mapping of the murine osteosclerosis (oc) mutation. 970 Jan 94

The thiamine transporter gene SLC19A2 was recently found to be mutated in thiamine responsive megaloblastic anaemia with diabetes and deafness (TRMA, Rogers syndrome), an early onset autosomal recessive disorder. We now report a novel G1074A transition mutation in exon 4 of the SLC19A2 gene, predicting a Trp358 to ter change, in a girl with consanguineous parents. In addition to the typical triad of Rogers syndrome, the girl presented with short stature, hepatosplenomegaly, retinal degeneration, and a brain MRI lesion. Both muscle and skin biopsies were obtained before high dose thiamine supplementation. While no mitochondrial abnormalities were seen on morphological examination of muscle, biochemical analysis showed a severe deficiency of pyruvate dehydrogenase and complex I of the respiratory chain. In the patient's fibroblasts, the supplementation with high doses of thiamine resulted in restoration of complex I activity. In conclusion, we provide evidence that thiamine deficiency affects complex I activity. The clinical features of TRMA, resembling in part those found in typical mitochondrial disorders with complex I deficiency, may be caused by a secondary defect in mitochondrial energy production.
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PMID:A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. 1097 58

We present a case of alpha-mannosidosis with its mutational analysis. She was referred to our hospital with the provisional diagnosis of mucolipidosis. She was the first child of second-degree relative parents. She had a coarse face with flat and wide nasal bridge, hepatosplenomegaly, umbilical hernia, lumbar gibbus, motor and mental retardation and deafness. On peripheral blood smear, lymphocytes revealed vacuoles and neutrophils contained some granules resembling Reilly bodies seen in mucopolysaccharidosis (MPS). Based on these findings, the diagnosis of alpha-mannosidosis was suspected. Her urine oligosaccharide chromatography showed an abnormal pattern with a heavy trisaccharide band. Enzyme studies on white cells confirmed a deficiency of alpha-mannosidase activity, which was 2.6 micromol/g/hr. Her DNA analysis showed a S453Y mutation.
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PMID:Alpha-mannosidosis and mutational analysis in a Turkish patient. 1271 72

We present three patients with congenital generalized lipodystrophy, sensorineural deafness, low birth weight, short stature, delayed cognitive development, and progressive bone changes characterized by overtubulation and rarefaction of long bones with dense metaphyseal striations occurring in adolescence. Abnormalities of lipid and carbohydrate metabolism, hepatosplenomegaly, acanthosis nigricans, and hirsutism were not found. Comparison of the condition of these patients with known syndromic lipodystrophies suggests that they represent a previously unrecognized genetic disorder. The occurrence in sibs born to consanguineous parents and a third patient from the same tribal unit suggest autosomal recessive inheritance.
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PMID:Congenital generalized lipodystrophy, mental retardation, deafness, short stature, and slender bones: a newly recognized syndrome? 1292 70

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive disorder characterized by diabetes mellitus (DM), progressive sensorineural deafness, and thiamine-responsive anemia. Mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter protein THTR-1 are responsible for the clinical features associated with TRMA syndrome. We report an African-American female with TRMA-syndrome associated with thyroid disease and retinitis pigmentosa caused by a novel mutation in the SLC19A2 gene. The patient presented at 12 months of age with paroxysmal atrial tachycardia and hepatosplenomegaly. One month later, she developed DM requiring intermittent insulin therapy. At 2-1/2 years of age, profound sensorineural hearing loss was discovered. By 4 years of age, daily insulin therapy (0.5 U/kg/day) was instituted and her insulin requirement gradually increased to 1.0 U/kg/day by 9 years of age. She developed optic atrophy, retinitis pigmentosa, and visual impairment by 12 years of age with severe restriction of peripheral vision by 16 years. At age 19, a thiamine-responsive normocytic anemia was discovered. She was diagnosed with autoimmune thyroiditis at 20 years and she experienced a psychotic episode associated with a mood disorder at age 21. With oral thiamine therapy, her insulin requirement decreased by 30% over a 20 month period. Molecular analysis revealed that the patient is homozygous for a missense mutation (C152T) in exon 1 of the SLC19A2 gene.
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PMID:Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome. 1499 41

Osteopetrosis is a heterogeneous family of rare human genetic disorders due to markedly decreased bone resorption. It is one among disorders causing osteosclerosis of the trabecular bone and/or hyperostosis of the cortical bone. Four types of human osteopetrosis have been clearly defined, but patients with atypical symptoms are frequent, suggesting that there are additional forms. The most severe expression of this condition in its malignant form is inherited as an autosomal recessive disorder and it is usually fatal before school age. It presents with failure to thrive, severe hepatosplenomegaly, pancytopenia and nerve compression leading to blindness and deafness during infancy. The case of a 2-month-old female child with severe hepatosplenomegaly, failure to thrive, nystagmus, pancytopenia, gengival hyperplasia, optic atrophy, absent evoked visual potential and increased bone density within the total skeleton, is reported. Diagnosis of autosomal recessive malignant osteopetrosis was established by transiliac bone biopsy. She underwent bone marrow transplantation, but died soon afterwards. This rare and mortal disorder of bone formation requires early diagnosis and immediate pharmacological treatment, consisting in administration of vitamin D, in order to enhance bone resorption and of prednisone to improve hematological indexes and, if possible, bone marrow transplantation in order to ameliorate quality of life and survival.
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PMID:Autosomal malignant osteopetrosis. From diagnosis to therapy. 1524 21

To understand a mechanism for the difference in clinical manifestations of congenital cytomegalovirus (CMV) infection between dizygotic twins, the placentas of the dizygotic twins were evaluated for the number of the cells infected with CMV by immunohistochemical and in situ hybridization studies. A Japanese woman with dizygotic twin pregnancy had immunoglobulin M antibodies to CMV at 15 weeks gestation. Intrauterine growth retardation was noted only in the first twin. At birth, CMV was isolated from urine culture in both twins. Clinical manifestations for CMV, such as petechiae, jaundice, hepatosplenomegaly, and deafness were more pronounced in the first twin than in the second twin. Immunohistochemical and in situ hybridization studies showed CMV-positive cells two or three times more densely distributed in the placenta of the first twin compared with the second twin. These data suggest the severity of CMV manifestations of dizygotic twins may be in accord with the number of CMV-positive cells in the placenta.
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PMID:Differential clinical manifestations of congenital cytomegalovirus infection between dizygotic twins: a case report. 1547 27

A 12-year-old girl presented with abdominal pain, fever, and hearing impairment of 6 months duration. She had massive hepatosplenomegaly and anemia. On the basis of her peripheral blood and bone marrow findings, she was diagnosed as chronic myeloid leukemia (CML) in chronic phase. Her hearing was assessed by brainstem evoked responses (BERA), which showed objective improvement in hearing with hydroxyurea. The rare occurrence of deafness in CML is reviewed and possible pathogenesis is discussed.
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PMID:Hearing loss in chronic myeloid leukemia. 1576 79


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