Assuntos
Neoplasias dos Ductos Biliares/etiologia , Carcinoma Hepatocelular/etiologia , Colangiocarcinoma/etiologia , Doença do Armazenamento de Colesterol Éster/complicações , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Neoplasias dos Ductos Biliares/patologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Doença do Armazenamento de Colesterol Éster/diagnóstico , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Adulto JovemRESUMO
BACKGROUND Cholesteryl ester storage disease (CESD), also known as lysosomal acid lipase deficiency (LAL-D), is a rare autosomal-recessive inheritable lysosomal storage disease. Since 2015, a causal treatment with sebelipase alfa, which replaces the missing LAL enzyme, has been approved. We report a fatal course of LAL-D in a female patient. CASE REPORT In 1979, CESD was first diagnosed in a 13-year-old female with marked hepatomegaly. At that time, no specific treatment for CESD was available and the spontaneous course of the disease had to be awaited. In 2013, a laparoscopic cholecystectomy for symptomatic gallstones was performed. The patient's CESD had caused a Child-Pugh A/B and Lab-MELD 14 cirrhosis with esophageal varices (grade III), a solitary fundal varix, as well as hepatosplenomegaly with thrombocytopenia. In 2016, the patient was admitted with compensated cirrhosis and splenomegaly for a ligature of esophageal varices which was complicated by vomiting of blood followed by severe coagulopathy and hemorrhagic shock. The dried blood test showed reduced acid lipase (0.03 nmol/spot*3 hours; reference range 0.2-2) and beta-galactosidase (0.08 nmol/spot*21 hours; reference range 0.5-3.2). Then 15 days after the esophageal varices bleed, the patient died due to multiorgan failure as a sequelae of advanced liver disease. CONCLUSIONS LAL-D should be included in the differential diagnosis of lipid metabolism disorder, hepatomegaly, and non-alcoholic fatty liver disease with fibrosis or cirrhosis. Causal treatment with sebelipase alfa should be introduced even in patients who have LAL-D and many years of clinically mild symptoms of this disease to prevent the serious sequelae of cirrhosis or cardiovascular complications.
Assuntos
Doença do Armazenamento de Colesterol Éster/complicações , Insuficiência de Múltiplos Órgãos/etiologia , Adolescente , Varizes Esofágicas e Gástricas/etiologia , Evolução Fatal , Feminino , Humanos , Cirrose Hepática/etiologiaAssuntos
Terapia de Reposição de Enzimas , Esterol Esterase/uso terapêutico , Doença de Wolman/tratamento farmacológico , Aterosclerose/etiologia , Estenose das Carótidas/etiologia , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/tratamento farmacológico , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hepatomegalia/etiologia , Humanos , Hipertensão Portal/etiologia , Hepatopatias/etiologia , Pessoa de Meia-Idade , Resultado do Tratamento , Veias Umbilicais , Doença de Wolman/complicações , Doença de WolmanRESUMO
Antecedentes: existe poca evidencia sobre el papel de los polimorfismos de CETP en sujetos obesos diabéticos. Objetivos: evaluar la asociación del polimorfismo (rs1800777) del gen CETP sobre parámetros antropométricos, perfil lipídico y adipocitoquinas en pacientes obesos con diabetes mellitus. Material y métodos: un total de 229 obesos con diabetes mellitus tipo 2 fueron reclutados. Una impedancia bioeléctrica, la presión arterial, ingesta dietética, ejercicio y bioquímica fueron analizados. Resultados: un total de 217 pacientes (94,8%) presentaron el genotipo GG y 12 pacientes GA (5,2%) (no se detectó el genotipo AA). El peso (delta: 14,4 ± 2,1 kg, p = 0,01), índice de masa corporal (delta: 2,2 ± 1,1 kg/m2, p = 0,01), masa grasa (delta: 11,2 ± 3,1 kg, p = 0,02), circunferencia de la cintura (delta: 3,9 ± 2,0 cm, p = 0,02), índice cintura-cadera (delta: 0,04 ± 0,02 cm; p = 0,01), triglicéridos (delta: 48,6 ± 9,1 mg / dl, p = 0,03) y leptina (delta: 58,6 ± 15,9 mg/dl, p = 0,02) fueron superiores en los pacientes con el alelo A que en los no portadores del alelo A. El HDL-colesterol fue menor en los portadores de alelo A que los no portadores (delta: 5,6 ± 1,1 mg/dl, p = 0,03). Manteniéndose las diferencias en los análisis multivariantes en los niveles de HDL colesterol, masa grasa y peso. Conclusión: nuestros resultados muestran una asociación del polimorfismo en posición +82 del gen CETP sobre los niveles de HDL colesterol, y parámetros de adiposidad en pacientes obesos con diabetes mellitus tipo 2 (AU)
Background: There is few evidence of cholesterol ester transfer protein (CETP) in subjects with obesity and diabetes mellitus. Objectives: We examined the association of the polymorphism (rs1800777) of CETP gene on anthropometric parameters, lipid profile and adipokines in subjects with obesity and diabetes mellitus type 2. Material and methods: A population of 229 obese subjects with diabetes mellitus type 2 was enrolled. An electrical bioimpedance, blood pressure, dietary intake, exercise and biochemical analyses were recorded. Results: Two hundred and seventeen subjects (94.8%) had genotype GG and 12 GA (5.2%) (genotype AA was not detected). Weight (delta: 14.4 ± 2.1 kg, p = 0.01), body mass index (delta: 2.2 ± 1.1 kg/m2, p = 0.01), fat mass (delta: 11.2 ± 3.1 kg, p = 0.02), waist circumference (delta: 3.9 ± 2.0 cm, p = 0.02), waist to hip ratio (delta: 0.04 ± 0.02 cm; p = 0.01), tryglicerides (delta: 48.6 ± 9.1 mg / dl, p = 0.03) and leptin levels (delta: 58.6 ± 15.9 mg/dl, p = 0.02) were higher in A allele carriers than non A allele carriers. Levels of HDL-cholesterol were lower in A allele carriers than non-carriers (delta: 5.6 ± 1.1 mg/dl, p = 0.03). In regression analysis, HDl cholesterol, weight and fat mass remained in the model with the SNP. Conclusion: Our results show an association of this CETP variant at position +82 on HDL cholesterol, levels and adiposity parameters in obese subjects with diabetes mellitus type 2 (AU)
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Ésteres do Colesterol/genética , Obesidade/complicações , Diabetes Mellitus Tipo 2/complicações , Dietética/métodos , Adipocinas/análise , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/genética , Obesidade/dietoterapia , Impedância Elétrica/uso terapêutico , Terapia por Exercício/tendências , Adipocinas/genética , Transtornos do Metabolismo dos Lipídeos/genética , Pressão Arterial/fisiologia , Índice de Massa CorporalRESUMO
Cholesteryl Ester Storage Disease (CESD), is a rare multisystem autosomal recessive disorder and belongs to the broad family of lysosomal storage disorders. It can present anytime from infancy and childhood to even adulthood. The clinical manifestations are generally severe in infants and with milder forms in adults. One of the prominent sites of involvement is liver. Due to low awareness of this condition among physicians including surgical pathologists, majority of the liver biopsies, especially from the adults are often misdiagnosed as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis or cryptogenic cirrhosis. Given the recent availability of safe and effective enzyme replacement therapy that can alter the natural course of CESD, the pathologists signing out adult and pediatric liver biopsies should be aware of this entity, thus contributing to timely patient management. This review discusses the clinical features, pathogenesis, diagnostic approach, differential diagnosis and management of CESD in adults.
Assuntos
Doença do Armazenamento de Colesterol Éster/complicações , Cirrose Hepática/etiologia , Adulto , Criança , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Serum lipoproteins influence cell cholesterol content by delivering and removing cholesterol to/from cells, functions mainly exerted by LDL and HDL, respectively. Especially in the case of HDL, structure and composition are crucial for function, beyond serum levels. Cholesteryl ester storage disease (CESD) is caused by LIPA gene mutations and reduced activity of lysosomal acid lipase (LAL), the enzyme responsible for hydrolysis of cholesteryl esters and TG. CESD patients typically present dyslipidaemia, liver damage and premature atherosclerosis. The objective of this work was to evaluate serum HDL cholesterol efflux capacity (CEC) and serum cholesterol loading capacity (CLC) in CESD pediatric patients and to study lipoprotein qualitative modifications. METHODS: HDL CEC was evaluated by radioisotopic techniques, serum CLC was measured by a fluorimetric assay, HDL subclasses were determined by two-dimensional electrophoresis. RESULTS: CESD patients (n = 3) displayed on average increased LDL cholesterol (+163%; p = 0.019), TG (+203; p = 0.012), phospholipids (+40%; p = 0.024) and lower HDL cholesterol (-57%; p = 0.012) compared to controls (n = 9). CESD HDL CEC was impaired both as a whole (average reduction of 26%; p < 0.0001) and with respect to specific membrane cholesterol transporters (-23% for aqueous diffusion; p = 0.005; -32% for ABCA1-efflux; p = 0.0002; -60% for SR-BI-efflux; p < 0.0001; -42% for ABCG1-efflux p = 0.0003). A marked reduction in the pre-ß HDL concentration (-69%; p = 0.012) was detected. Finally, CESD serum CLC was significantly increased (+21%; p = 0.0007). CONCLUSION: These new data demonstrate that the pro-atherogenic modifications of serum include disturbances in lipoprotein functions involved in cell cholesterol homeostasis occurring from very early age in CESD patients.
Assuntos
Aterosclerose/sangue , Doença do Armazenamento de Colesterol Éster/sangue , Lipoproteínas/sangue , Aterosclerose/complicações , Transporte Biológico , Estudos de Casos e Controles , Criança , Pré-Escolar , Colesterol/sangue , Doença do Armazenamento de Colesterol Éster/complicações , HDL-Colesterol/sangue , Eletroforese em Gel Bidimensional , Feminino , Fluorometria , Células Espumosas/citologia , Humanos , Lipoproteínas HDL/sangue , Masculino , Fatores de RiscoRESUMO
Cholesterol ester storage disease is an exceptionally rare dyslipidemia with less than 150 cases reported in the medical literature. The diagnosis of Cholesterol Ester Storage Disease is often missed by virtue of the fact that the symptoms mimic both inborn metabolic defects and hepatic steatosis. Patients with Cholesterol Ester Storage Disease usually present with atypical complaints including abdominal pain from altered gut motility. Blood analysis typically reveals abnormal liver function tests with coincident dyslipidemia. We present a case of a young woman with Cholesterol Ester Storage Disease who was followed over two decades. We discuss issues common to her initial protracted diagnosis with management options over time.
Assuntos
Dor Abdominal/complicações , Dor Abdominal/diagnóstico , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/diagnóstico , Dislipidemias/complicações , Dislipidemias/diagnóstico , Dor Abdominal/tratamento farmacológico , Adulto , Doença do Armazenamento de Colesterol Éster/tratamento farmacológico , Diagnóstico Diferencial , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêuticoRESUMO
Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early.
Assuntos
Doença do Armazenamento de Colesterol Éster/tratamento farmacológico , Terapia de Reposição de Enzimas , Doença de Wolman/tratamento farmacológico , Criança , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/diagnóstico , Humanos , Lactente , Doença de Wolman/complicações , Doença de Wolman/diagnóstico , Doença de WolmanRESUMO
Cholesteryl ester storage disease (CESD) is caused by deficient lysosomal acid lipase (LAL) activity, predominantly resulting in cholesteryl ester (CE) accumulation, particularly in the liver, spleen, and macrophages throughout the body. The disease is characterized by microvesicular steatosis leading to liver failure, accelerated atherosclerosis and premature demise. Although CESD is rare, it is likely that many patients are unrecognized or misdiagnosed. Here, the findings in 135 CESD patients described in the literature are reviewed. Diagnoses were based on liver biopsies, LAL deficiency and/or LAL gene (LIPA) mutations. Hepatomegaly was present in 99.3% of patients; 74% also had splenomegaly. When reported, most patients had elevated serum total cholesterol, LDL-cholesterol, triglycerides, and transaminases (AST, ALT, or both), while HDL-cholesterol was decreased. All 112 liver biopsied patients had the characteristic pathology, which is progressive, and includes microvesicular steatosis, which leads to fibrosis, micronodular cirrhosis, and ultimately to liver failure. Pathognomonic birefringent CE crystals or their remnant clefts were observed in hepatic cells. Extrahepatic manifestations included portal hypertension, esophageal varices, and accelerated atherosclerosis. Liver failure in 17 reported patients resulted in liver transplantation and/or death. Genotyping identified 31 LIPA mutations in 55 patients; 61% of mutations were the common exon 8 splice-junction mutation (E8SJM(-1G>A)), for which 18 patients were homozygous. Genotype/phenotype correlations were limited; however, E8SJM(-1G>A) homozygotes typically had early-onset, slowly progressive disease. Supportive treatment included cholestyramine, statins, and, ultimately, liver transplantation. Recombinant LAL replacement was shown to be effective in animal models, and recently, a phase I/II clinical trial demonstrated its safety and indicated its potential metabolic efficacy.
Assuntos
Doença do Armazenamento de Colesterol Éster/terapia , Colesterol/sangue , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/diagnóstico , Doença do Armazenamento de Colesterol Éster/genética , Doença do Armazenamento de Colesterol Éster/patologia , Terapia de Reposição de Enzimas , Humanos , Fígado/patologia , Transplante de Fígado , Triglicerídeos/sangue , Doença de Wolman/complicações , Doença de WolmanRESUMO
We report the case of a 13-year-old boy with a longstanding history of unspecific hepatomegaly. The morphological investigations were diagnostic of a cholesterol ester storage disease (CESD), a rare autosomal recessive inherited disease with deficient activity of lysosomal acid lipase (LAL). The combination of hepatomegaly with accumulation of macrophages and ultrastructural evidence of lysosomal lipid storage are groundbreaking for the diagnosis. The probability of a underdiagnosis or false disease classification, for example as nonalcoholic steatohepatitis (NASH), is high, particularly with regard to genetic data which indicate a higher incidence of the disease.
Assuntos
Doença do Armazenamento de Colesterol Éster/patologia , Adolescente , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/genética , Diagnóstico Diferencial , Hepatomegalia/complicações , Hepatomegalia/patologia , Humanos , Masculino , Esterol Esterase/deficiência , Esterol Esterase/genéticaAssuntos
Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/patologia , Doença do Armazenamento de Colesterol Éster/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Transplante de Fígado/métodos , Biópsia por Agulha , Criança , Doença do Armazenamento de Colesterol Éster/complicações , Progressão da Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Testes de Função Hepática , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/patologia , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Cholesterol ester storage disease is a rare autosomal recessive storage disorder resulting from lysosomal acid lipase deficiency. Two siblings manifested with hepatosplenomegaly, ptosis, and bilateral external ophthalmoplegia. Evaluation revealed hyperlipidemia and bilateral adrenal calcifications. Leukocyte acid lipase levels were significantly low in both the patients, compared with controls, suggesting a diagnosis of cholesterol ester storage disease. Ptosis and external ophthalmoplegia have hitherto not been reported in cholesterol ester storage disease.
Assuntos
Doenças do Sistema Nervoso Central/etiologia , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/diagnóstico , Blefaroptose/etiologia , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/fisiopatologia , Pré-Escolar , Doença do Armazenamento de Colesterol Éster/tratamento farmacológico , Dieta com Restrição de Gorduras , Potencial Evocado Motor , Glucocorticoides/uso terapêutico , Hepatomegalia/etiologia , Humanos , Índia , Lactente , Lipídeos/sangue , Masculino , Oftalmoplegia/etiologia , Prednisolona/uso terapêutico , Radiografia Abdominal , Doenças Raras , Irmãos , Esplenomegalia/etiologia , Esterol Esterase/deficiência , Tomografia Computadorizada por Raios X , Vômito/etiologia , Doença de Wolman/complicações , Doença de Wolman/diagnóstico , Doença de Wolman/tratamento farmacológicoRESUMO
Cholesteryl ester storage disease (CESD) is an autosomal recessive disorder resulting from lysosomal acid lipase deficiency and is usually characterized by hepatomegaly and hyperlipidemia. This paper reports a two-year-old boy who had hepatosplenomegaly, hyperlipidemia and hypertransaminasemia determined incidentally. The liver biopsy sample was orange-yellow in appearance. Microscopically, microvesicular steatosis and birefringent crystals were seen in liver biopsy. The diagnosis of CESD was confirmed by the reduced human acid lipase activity in peripheral leukocytes. Simvastatin therapy was given and tolerated without side effects. Our patient is the youngest reported case in the literature treated with 3-hydroxy 3-methyl glutaryl (HMG) CoA reductase inhibitor.
Assuntos
Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/tratamento farmacológico , Hepatomegalia/etiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Sinvastatina/uso terapêutico , Biópsia , Pré-Escolar , Doença do Armazenamento de Colesterol Éster/patologia , Hepatomegalia/patologia , Humanos , MasculinoRESUMO
The goal of this paper is to present a clinical case of a 4 year old boy, with hepatomegaly, splenomegaly and intestinal lipid infiltration due to a inborn error of lipid metabolism known as cholesterol ester storage disease. The main clinical manifestations were hepatomegaly, splenomegaly, hypertriglyceridemia, hypercholesterolemia. Duodenal endoscopy showed a yellow appearance of the mucous, and the histological study revealed the presence of macrophages with granular material. Liver biopsy showed steatosis infiltration at the hepatocytes, and macrophages with lipids. This disease is due to a lisosomal acid lipase partial deficiency, that is a glicoprotein that metabolize the hydrolysis of ester of cholesterol and triglycerides. The name of this pathology is cholesterol ester storage disease, but when the deficiency is total the name is Wolman's disease. We conclude that in all the children whit a clinical picture of hepatomegaly, splenomegaly, hypertriglyceridemia and hypercholesterolemia it is obligatory to rule out an inborn error of lipid metabolism like Wolman's disease or cholesterol ester storage disease.
Assuntos
Doença do Armazenamento de Colesterol Éster/complicações , Hepatomegalia/etiologia , Esplenomegalia/etiologia , Doença do Armazenamento de Colesterol Éster/patologia , Doença do Armazenamento de Colesterol Éster/terapia , Duodeno/patologia , Endoscopia do Sistema Digestório , Hepatomegalia/patologia , Humanos , Lactente , Fígado/patologia , Masculino , Esplenomegalia/patologiaRESUMO
Few cases of asymptomatic cholesteryl ester storage disease (CESD) due to low enzymatic activity of human lysosomal acid lipase/cholesteryl ester hydrolase (hLAL) have been reported thus far in adults Here, we describe a 51-year-old man with a long clinical history of mixed hyperlipoproteinemia and severe premature atherosclerosis, but with no signs of hepatomegaly, liver dysfunction, or splenomegaly. The disease was discovered by chance in a biopsy performed because of suspected liver cancer (proven to be a cholangiocarcinoma). Residual hLAL activity in peripheral leukocytes was determined to be 6% of control values. DNA sequence and restriction fragment length polymorphism analysis demonstrated that the patient was a compound heterozygote for the prevalent CESD exon 8 splice site mutation (G934A) and the deletion of a C (nucleotide 673, 674, or 675) in exon 6 of the hLAL gene, resulting in premature termination of protein translation at residue 195. The patient died of liver failure as a consequence of extensive tumor infiltration at age 52. Lipid analysis revealed moderate cholesteryl ester storage in the liver and in the suprarenal cortex, and massive accumulation in the testicular histiocytes and Leydig cells, resulting in a pronounced secondary atrophy of the seminiferous tubules. Our case study demonstrates that hepatomegaly is an inconstant feature, even in CESD patients compound heterozygous for a Wolman mutation which results in complete loss of hLAL enzymic activity. It also highlights the need to be aware of this condition as it may be underdiagnosed.
Assuntos
Arteriosclerose/complicações , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/fisiopatologia , Hipercolesterolemia/complicações , Neoplasias Hepáticas/complicações , Adulto , Sequência de Bases/genética , Doença do Armazenamento de Colesterol Éster/genética , DNA/genética , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Linhagem , Polimorfismo de Fragmento de RestriçãoRESUMO
A case of long-standing subclinical cholesteryl ester storage disease (CESD) manifesting as hyperlipoproteinaemia type IIb without any hepatomegaly is described. The patient underwent surgical vascular interventions because of accelerated atherosclerosis, which dominated his middle age. CESD was an incidental finding when a liver biopsy specimen was taken because liver malignancy was suspected; the patient's condition proved to be due to a cholangiocarcinoma, which led to his death at the of age 52. The autopsy showed moderate-intensity storage in the set of cells characterized by constitutional high-level receptor-mediated LDL endocytosis (hepatocytes, adrenal cortical cells) and also revealed storage in the Leydig cells. The severity with which histiocytes were affected varied regionally, ranging from minimal detectable storage or none at all (gut, lymph nodes, spleen) to extreme lysosomal expansion by cholesteryl ester liquid crystals (bone marrow) or by ceroid (lung, testicular stroma), or by both (liver). The density of the histiocytic population did not correlate with the degree to which parenchymal cells were affected except in the testicular stroma, where it was prominent. The patient was a mixed heterozygote for the G934A and DeltaC(673-5) mutations.
Assuntos
Arteriosclerose/complicações , Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/complicações , Doença do Armazenamento de Colesterol Éster/patologia , Células Intersticiais do Testículo/patologia , Doenças Testiculares/patologia , Adulto , Doença do Armazenamento de Colesterol Éster/complicações , Doença do Armazenamento de Colesterol Éster/metabolismo , Cromatografia em Camada Delgada , Evolução Fatal , Humanos , Hiperlipoproteinemia Tipo II/etiologia , Células Intersticiais do Testículo/metabolismo , Lipase/deficiência , Lipase/genética , Lisossomos/enzimologia , Masculino , Pessoa de Meia-Idade , Doenças Testiculares/complicações , Doenças Testiculares/metabolismoRESUMO
A 36-year-old woman was admitted for hepatosplenomegaly and anemia. Bone marrow cytology showed "sea-blue histiocytes", vacuolated macrophages and plasma cells. As primary liver disease, malignancy or hematologic disorders were excluded, and plasma chitotriosidase activity was increased 27-fold over control, the presence of a lysosomal storage disease was suspected. Biochemical analysis of skin fibroblasts revealed normal glucocerebrosidase and sphingomyelinase activity, but lipid analysis showed a more than 15-fold accumulation of cholesterol esters within the cells. The activity of lysosomal acid lipase (LAL) in fibroblast homogenates was decreased to 12% of control subjects. Mutational analysis of the patient's blood showed the homozygous G-->A mutation at position -1 of the exon 8 splice donor site (E8SJM-allele) known for adult cholesteryl ester storage disease (CESD); the polymorphic background was that of the complex haplotype -6Thr, 2Gly, 894 G-->A. Based on clinical, laboratory, cytological and and biochemical findings, CESD can clearly be separated from other more frequent inherited lysosomal storage diseases, e.g. atypical forms of Gaucher disease.