-
Molecular Genetics and Metabolism 2017The eponym Niemann-Pick disease (NPD) refers to a group of patients who present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as... (Review)
Review
The eponym Niemann-Pick disease (NPD) refers to a group of patients who present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features including hepatosplenomegaly, pulmonary insufficiency and/or central nervous system (CNS) involvement. Due to the pioneering work of Roscoe Brady and co-workers, we now know that there are two distinct metabolic abnormalities that account for NPD. The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM; "types A & B" NPD), and the second is due to defective function in cholesterol transport ("type C" NPD). Herein only types A and B NPD will be discussed. Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement. They rarely survive beyond 2-3years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Intermediate patients also have been reported with mild to moderate neurological findings. All patients with types A and B NPD have mutations in the gene encoding ASM (SMPD1), and thus the disease is more accurately referred to as ASM deficiency (ASMD). Herein we will review the clinical, pathological, biochemical, and genetic findings in types A and B NPD, and emphasize the seminal contributions of Dr. Brady to this disease. We will also discuss the current status of therapy for this disorder.
Topics: Age of Onset; Animals; Cholesterol; Disease Progression; Female; History, 20th Century; History, 21st Century; Humans; Male; Mutation; Niemann-Pick Diseases; Sphingomyelin Phosphodiesterase
PubMed: 28164782
DOI: 10.1016/j.ymgme.2016.12.008 -
Pathobiology : Journal of... 2016We present a brief review of Gaucher disease (GD), the most common lysosomal storage disease. GD is a rare autosomal recessive disorder characterized by the defective... (Review)
Review
We present a brief review of Gaucher disease (GD), the most common lysosomal storage disease. GD is a rare autosomal recessive disorder characterized by the defective function of the catabolic enzyme β-glucocerebrosidase (GBA), leading to an accumulation of its substrate, glucocerebroside. Clinical signs and symptoms include neurological dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia and thrombocytopenia. Enzyme replacement therapy with recombinant GBA is the mainstay of treatment for GD, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.
Topics: Enzyme Replacement Therapy; Gaucher Disease; Genetic Therapy; Glucosylceramidase; Humans; Hypersplenism; Splenomegaly
PubMed: 26588331
DOI: 10.1159/000440865 -
The Veterinary Clinics of North... May 2022Cardiac disease is relatively common in middle-aged to older ferrets and may comprise acquired or congenital disorders leading to problems with conduction,... (Review)
Review
Cardiac disease is relatively common in middle-aged to older ferrets and may comprise acquired or congenital disorders leading to problems with conduction, contractility, or outflow. Clinical signs are often seen in advanced stages of the disease, with lethargy, hind limb weakness, ascites, hepatosplenomegaly, and respiratory distress owing to pleural effusion or lung edema being prominent features. Diagnostic workup and therapeutic intervention largely follow guidelines such as those established for dogs and cats, with feline doses often serving as a starting point for therapy.
Topics: Animals; Cardiology; Cat Diseases; Cats; Dog Diseases; Dogs; Ferrets; Heart Diseases
PubMed: 35422266
DOI: 10.1016/j.cvex.2022.01.007 -
Proceedings (Baylor University. Medical... 2022Murine typhus is a rare condition caused by the gram-negative bacterium which classically presents with the triad of fever, rash, and headache. Herein we report a rare...
Murine typhus is a rare condition caused by the gram-negative bacterium which classically presents with the triad of fever, rash, and headache. Herein we report a rare presentation of murine typhus in an adult who presented predominantly with fever and gastrointestinal symptoms. Initial imaging showed cardiomegaly and hepatosplenomegaly, which led to further workup revealing rickettsial disease. Although this illness is considered a rare diagnosis in the emergency department, every person with a pet that might have fleas is susceptible to it.
PubMed: 35991722
DOI: 10.1080/08998280.2022.2078640 -
Cureus Jun 2021Hemophagocytic lymphohistiocytosis (HLH) is a fatal syndrome, which can be primary or triggered by a systemic disease or an infection. The commonly reported infectious...
Hemophagocytic lymphohistiocytosis (HLH) is a fatal syndrome, which can be primary or triggered by a systemic disease or an infection. The commonly reported infectious causes of secondary HLH include Epstein-Barr virus (EBV), cytomegalovirus (CMV), mycobacterium, and leishmaniasis among other infections. In this case report, we report a 50-year-old woman with brucellosis-related HLH after presenting with prolonged fever, hepatosplenomegaly, and cytopenia.
PubMed: 34277268
DOI: 10.7759/cureus.15677 -
Archives of Disease in Childhood Nov 1980Two siblings developed a fulminant fatal myeloproliferative disease at 7 and 8 weeks of age. The illness presented with pallor, haemorrhagic symptoms, and...
Two siblings developed a fulminant fatal myeloproliferative disease at 7 and 8 weeks of age. The illness presented with pallor, haemorrhagic symptoms, and hepatosplenomegaly, and the blood picture was that of pancytopenia and leucoerythroblastosis. Bone marrow histology showed reduced haemopoiesis with generalised fibrosis. Histiocytes were present, but haemophagocytosis was not prominent. There was evidence of extramedullary haemopoiesis in the spleen, with a chronic inflammatory infiltrate of other organs. The condition closely resembles acute idiopathic myelofibrosis of infancy, but the early onset with severe pancytopenia and the histological appearances may arouse suspicion of the possible familial nature of the condition. Although clinically resembling familial haemophagocytic reticulosis, the uncharacteristic bone marrow, liver, and spleen histology serve to exclude this diagnosis.
Topics: Bone Marrow; Female; Humans; Infant; Male; Primary Myelofibrosis
PubMed: 7436463
DOI: 10.1136/adc.55.11.888 -
Archives of Disease in Childhood Oct 1991The importance of accurate pathological diagnosis is emphasised in the case of a newborn infant who presented with alopecia, a generalised erythrodermatous skin...
The importance of accurate pathological diagnosis is emphasised in the case of a newborn infant who presented with alopecia, a generalised erythrodermatous skin eruption, and hepatosplenomegaly. She subsequently developed generalised lymphadenopathy and recurrent septicaemia and died aged 2 months. The histological findings of widespread lymphocytic, histiocytic, and eosinophilic tissue infiltration, associated with thymic hypoplasia, were consistent with autosomal recessive Omenn's disease.
Topics: Alopecia; Bone Marrow; Dermatitis, Exfoliative; Female; Genes, Recessive; Hepatomegaly; Humans; Infant, Newborn; Lymph Nodes; Lymphatic Diseases; Skin; Splenomegaly; Syndrome
PubMed: 1835343
DOI: 10.1136/adc.66.10.1247