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

Eight children with human immunodeficiency virus (HIV) infection had symptomatic cardiac dysfunction. The median age was 1.4 years (range 0.2 to 7.9 years). All had hepatosplenomegaly, fever, pneumonia with tachypnea, and tachycardia ascribed to infection and anemia. An S3 gallop was present in six of eight. All had normal creatine phosphokinase values. Chest x-rays did not aid in the diagnosis of cardiac dysfunction. ECG showed flattened T waves in five of eight with left ventricular hypertrophy, right ventricular hypertrophy, or both in seven of eight. Results of echocardiography showed decreased left ventricular function in all eight, despite anemia, with dilated left ventricular myopathy in six, concentric left ventricular wall thickening in two of eight, an enlarged right ventricle in two, and pericardial fluid in three. Medical therapy improved cardiac function in all. All patients subsequently died of noncardiac causes. Results of autopsies on four of eight patients showed focal myocarditis in two (with cytomegalovirus inclusions in one) and dilated cardiomyopathy in two others. We conclude: (1) Preexistent hepatosplenomegaly, fever, infection, and anemia result in physical findings that mimic findings of heart failure, thereby masking the occurrence of cardiac dysfunction; (2) an S3 gallop may indicate the presence of impaired heart function when other clinical signs are masked; (3) confirmation of cardiac compromise may be accomplished by noninvasive evaluation with echocardiography and (4) medical therapy can improve cardiac dysfunction in HIV-infected children.
 ...
PMID:Symptomatic cardiac dysfunction in children with human immunodeficiency virus infection. 252 16

Described in this paper is a 73-year-old Ashkenazi Jew affected with adult type 1 (nonneuronopathic form) Gaucher's disease. This was diagnosed at the age of 46 during an investigation of hepatosplenomegaly. No other members of his family were known to be affected with this disorder. The patient has been periodically examined at our Institute and has been free of all cardiopulmonary symptoms. This description emphasizes his echocardiographic pattern which revealed left ventricular hypertrophy, a septal muscular hump, and an extended area of apical akinesis. Myocardial involvement in Gaucher's disease has seldom been reported in the past.
 ...
PMID:Unusual echocardiographic pattern in Gaucher's disease. 399 19

A 77-year-old male had been noticing progressive weakness of the legs for three years. By the age of 75 he had difficulty in climbing stairs. On admission, serum level of CPK was moderately high. There were weakness and atrophy of the proximal muscles. Deep tendon reflexes were depressed. Sensation was normal. The electromyogram and the biopsy of the femoral quadriceps muscles showed nonspecific changes. In 1989, he developed difficulty in walking and had congestive heart failure. On the second admission, moist rales were heard over the chest, and pitting edema was present in the lower extremities. The chest roentgenogram showed a cardiothoracic ratio of 63% and bilateral pleural effusion. The electrocardiogram showed atrial flutter with 2:1 conduction, QS in V1-3, rS in V4, and ST depression and T inversion in V5,6. The echocardiogram revealed a thick left ventricular wall and impaired left ventricular contraction (EF 22%). Macroglossia, hepatosplenomegaly and renal dysfunction were not noted. Congestive heart failure progressed and he suddenly died of ventricular tachycardia in December 1989. At autopsy, skeletal muscle fibers varied in size and showed fiber splitting. A cellular infiltration was observed in the stroma. Amyloid deposit was positively stained with Congo red. The heart weight was 570 g with marked left ventricular hypertrophy and moderate bilateral atrial dilatation. In both atria and ventricles, extensive amyloid deposition was found around myocardial fibers as well as in perivascular spaces. Amyloid was present also in the liver, the kidneys, the gastrointestinal tracts, and the other organs.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[A case of primary systemic amyloidosis with skeletal muscle atrophy and congestive heart failure]. 848 88

In adults, elevated transaminases and hepatomegaly, often mild, with moderate to massive idiopathic splenomegaly might hint to a lysosomal storage disease (LSD). In most of these cases, hepatosplenomegaly does not eventually lead to cirrhosis, hepatocellular carcinoma or cholestasis. Nevertheless, the hepatic clinical findings might be the incentive for the patient to present at the physician's office. Many of the currently known >50 lysosomal storage diseases might manifest in liver: out of these, the most important ones in adults are: Gaucher disease, cholesterol ester storage disease (CESD) and the Niemann-Pick diseases. An increase of plasma chitotriosidase should alert the physician for the presence of an LSD. For Gaucher's disease, enzyme supplementation and substrate deprivation constitute effective therapeutic options. Fabry's disease, the most prevalent lysosomal storage disease, does usually not affect the liver, but causes painful episodes of hands' or feet pain (acroparesthesias), left ventricular hypertrophy, renal failure, early stroke and decreased life expectancy. The emerging advent of effective therapeutic options and the cumulative prevalence of lysosomal storage diseases urge the hepatologist to add these diagnostic pathways to the clinical repertoire.
 ...
PMID:Lysosomal storage diseases as differential diagnosis of hepatosplenomegaly. 2095 64

Hunter syndrome (mucopolysaccharidosis II, MPS II) is a rare, X-linked disorder of glycosaminoglycan (GAG) catabolism caused by a deficiency in the activity of the lysosomal enzyme, iduronate-2-sulfatase (I2S). In this study, the medical records of 75 Korean patients with Hunter syndrome (74 males, 1 female) were retrospectively reviewed to investigate the frequency of organ involvement and survival at a single center. The three most common symptoms of organ involvement were hepatosplenomegaly (99%), facial dysmorphism (97%), and frequent otitis media (91%). Cardiovascular involvement was also common including valvular abnormalities (89%), left ventricular hypertrophy (68%), and hypertension (30%). The 19 patients who died had a median age of 16.8 years at the time of death. Four of them died within 1 year of the start of enzyme replacement therapy; autopsy showed myocardial infarction with severe coronary artery disease in one patient. Two other patients died due to pneumonia and sleep apnea. In one case, the cause of death was not investigated. The high incidence of hypertension, and the presence of valvular heart disease indicates that close cardiac monitoring is mandatory in all patients with Hunter syndrome, especially relatively older patients even if they are being treated with enzyme replacement therapy.
 ...
PMID:Retrospective analysis of the clinical manifestations and survival of Korean patients with mucopolysaccharidosis type II: emphasis on the cardiovascular complication and mortality cases. 2210 82

The SLC29A3 gene, encoding hENT3, a member of the equilibrative nucleoside transporter family, has recently been found mutated in Faisalabad histiocytosis, pigmented hypertrichotic dermatosis with insulin-dependent diabetes, familial sinus histiocytosis with massive lymphadenopathy (SHML), and H syndromes. We here report clinical and genetic findings of an Egyptian family with H syndrome. We describe two siblings, a 19-yr old girl and a 15-yr old boy, of consanguineous parents. From 5 yr of age, the girl developed bilateral flexion deformity of interphalengeal joints and insulin-dependent diabetes mellitus. At age 7 yr, prominent hyperpigmented patches appeared on the skin at lower limbs, genitalia, and trunk. On clinical examination, she had hepatosplenomegaly, generalized lymphadenopathy, left ventricular hypertrophy, sensorineural hearing loss, hypogonadism, short stature, and characteristic dysmorphic features. Her brother had fixed flexion contractures of the feet, profound sensorineural hearing loss, characteristic dysmorphic features, but no diabetes. DNA sequence analysis revealed a homozygous mutation (c.300+1G>C) in SLC29A3 in both siblings. The phenotype and genotype of the siblings were compatible with that of the H syndrome, although the features were overlapping with those found in pigmented hypertrichotic dermatosis with insulin-dependent diabetes, familial SHML, and Faisalabad histiocytosis, indicating that these four syndromes may be regarded as one disease with varying phenotypic features. A new, common name for these conditions is warranted.
...
PMID:An Egyptian family with H syndrome due to a novel mutation in SLC29A3 illustrating overlapping features with pigmented hypertrichotic dermatosis with insulin-dependent diabetes and Faisalabad histiocytosis. 2298 30

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the lysosomal hydrolase a-L-Iduronidase leading to accumulation of the GAGs, dermatan sulfate, and heparan sulphate, The disease spectrum includes a disorder with severe involvement and CNS disease Hurler disease (HPS I H) a chronic disease without CNS disease Scheie disease (HPS I S5) and the intermediate Hurler/Scheie disease(HPS I HIS).The urine GAGs pattern. confirmed by Iduronidase enzyme assay is diagnostic. Over 200 mutations exist. Genotype / phenotype correlation is poor but two nonsense mutations results in Hurler disease.The skeletal disease dysostosis multiplex (DM) is seen in severe variants of MPS I. The hypoplastic odontoid putting these patients at high risk of cervical cord damage. MPS IH (Hurler Disease) affected infants develop a spinal 'gibbus' deformity, persistent nasal discharge, middle ear effusions and frequent upper respiratory infection. They have "coarse", facial features, and an enlarged tongue. . Progressive upper airway disease leads to obstructive sleep apnoea. Corneal clouding and cognitive impairment appears, growth ceases. Joint stiffness and contractures limit mobility. Cardiac disease is universal. Death occurs before 10 years. SCHEIE patients are diagnosed as teenagers with hepatomegaly, joint contractures, cardiac valve abnormalities and corneal clouding . Prolonged survival with considerable disability without cognitive impairment is usual. MPS IH/S Hurler/Scheie. is diagnosed by 6.5 years, with variable skeletal and visceral manifestations without cognitive involvement. Joint stiffness, corneal clouding, , umbilical hernia, abnormal facies, hepatomegaly, joint contractures, and cervical myelopathy occur. Patients die in their 20s .Haematopoietic stem cell transplantation (HSCT) the standard treatment of MPS IH for 30 years is unpredictable .When performed before 2 years it can stabilize cognitive impairment. Hepatosplenomegaly, urine GAGs excretion, upper airways obstruction and cardiomyopathy improve . The coarse hair and facial features soften and corneas partly clear,but dysostosis multiplex and cervical instability are not improved. Enzyme replacement therapy (ERT) in patients with MPS IH is associated with improved GAG excretion, left ventricular hypertrophy,sleep studies and liver size. The standard treatment of MPS IHIS and MIPS IS is ERT a-L-Iduronidase, laronidase, a life-long therapy. GAG excretion is reduced, respiratory function and physical endurance improve. Joint mobility improves but not dural thickening, cardiac valve lesions or eye changes. MPS I mice have been successfully treated with IDUA-expressing mesenchymaf stem cells . Gene therapy may be developed for MPS I, via an ex vivo approach demonstrated to improve even skeletal outcomes in animal models.
 ...
PMID:Mucopolysaccharidosis type I. 2534 91

Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma. POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder (PCD). The occurrence of AITL with POEMS syndrome has rarely been reported in the literature. The current study presents the case of a 53-year-old male who presented with a rapidly proliferative lymph node on the left neck, which was identified as an AITL on biopsy. The patient also exhibited the complications of polyneuropathy, M-proteinemia, hepatosplenomegaly, left ventricular hypertrophy, endocrinopathy and skin changes, and was therefore diagnosed with POEMS syndrome. To the best of our knowledge, the present study is the first to report a case of AITL with POEMS syndrome. The findings in this case suggest that the aberrant clones of B cells can also be caused by AITL.
 ...
PMID:T-cell lymphoma with POEMS syndrome. 2566 4

AL amyloidosis is due to deposition of protein derived from immunoglobulin light chain fragments. It is a systemic disorder in which deposition of plasma proteins can adversely affect function of the heart, liver, kidneys, and peripheral nerves. Deposition in the heart results in a decrease in the amplitude of the electrical activity of the heart and can be an early clue to the diagnosis. A 63-year-old male admitted for volume overload was found to have nephrotic range proteinuria, progressive renal insufficiency (Creatinine 4.0 increased from his baseline 0.9), and hypoalbuminemia. On exam, he had diffuse anasarca and peripheral neuropathy. A renal biopsy showed AL amyloidosis, lambda related, involving the glomeruli, interstitium, and arterial walls. Bone marrow biopsy showed 30% plasma cells with lambda light chain predominance. Serum free light chains were elevated. Lamda was 11.50 mg/dL and kappa was 5.12 mg/dL. In retrospective review of his chart, an EKG with low voltage and anterior pseudo-infarct pattern was first apparent on an admission for stroke two years prior. Echocardiogram showed mild concentric left ventricular hypertrophy. The patient was started on chemotherapy with Bortezomib. The differential of a low-voltage EKG includes many common pulmonary and chest wall (COPD, obesity) as well as pericardial diseases (effusions), but also important rarer infiltrative diseases including sarcoidosis and amyloidosis. Amyloidosis of the heart can cause progressive irreversible heart failure, but its progress can be altered if identified early. Physicians should consider amyloidosis when faced with a low-voltage EKG along with systemic symptoms including nephrotic range proteinuria, peripheral neuropathy, hepatosplenomegaly, and macroglossia.
 ...
PMID:Low voltage criteria EKG as a harbinger of systemic disease. 3125 62