121
(74.2%)

Abetalipoproteinemia

Acanthocytosis Cholestasis Cirrhosis Hypocholesterolemia

Autosomal recessive inheritance

A severe, familial hypobetalipoproteinemia characterized by permanently low levels (below the 5th percentile) of apolipoprotein B and LDL cholesterol, and by growth delay, malabsorption, hepatomegaly, and neurological and neuromuscular manifestations.

122
(74.2%)

Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome

Jaundice Low levels of vitamin E Polycythemia Splenomegaly

Autosomal recessive inheritance

123
(74.1%)

Congenital dyserythropoietic anemia type I

Anemia Anisopoikilocytosis Hypertension Jaundice

Congenital dyserythropoietic anemiatype I (CDA I) is a hematologic disorder of erythropoiesis characterized by moderate to severe macrocytic anemia occasionally associated with limb or nail deformities and scoliosis.

124
(73.9%)

AGel amyloidosis

Abnormal spleen morphology Anemia Dermatological manifestations of systemic disorders Proteinuria

Autosomal dominant inheritance

A rare, systemic amyloidosis characterized by a triad of ophthalmologic, neurologic and dermatologic findings due to the deposition of gelsolin amyloid fibrils in these tissues. Clinical manifestations include corneal lattice dystrophy, cranial neuropathy, especially affecting the facial nerve, bulbar signs, cutis laxa, increased skin fragility, and less commonly peripheral neuropathy and renal failure.

124
(73.9%)

Pulmonary arteriovenous malformation

Anemia Cyanosis Hyperammonemia Polysplenia

Autosomal recessive inheritance

Pulmonary arteriovenous malformation (PAVM) describes an anatomic communication between a pulmonary artery and a pulmonary vein leading to a right to left extracardiac shunt that can be asymptomatic or can lead to varying manifestations such as dyspnea, hemoptysis, and neurological symptoms.

124
(73.9%)

Truncus arteriosus

Asplenia Cyanosis Diabetes mellitus Hemolytic anemia

Truncus arteriosus (TA) is a rare congenital cardiovascular anomaly characterized by a single arterial trunk arising from the heart by means of a single semilunar valve (i.e. truncal valve). Pulmonary arteries originate from the common arterial trunk distal to the coronary arteries and proximal to the first brachiocephalic branch of the aortic arch. TA typically overrides a large outlet ventricular septal defect (VSD). The intracardiac anatomy usually displays situs solitus and atrioventricular (AV) concordance.

124
(73.9%)

Choanal atresia

Accessory spleen Anemia Cyanosis Edema

Choanal atresia (CA) is a congenital anomaly of the posterior nasal airway characterized by the obstruction of one (unilateral) or both (bilateral) choanal aperture(s), with clinical manifestations ranging from acute respiratory distress to chronic nasal obstruction.

128
(73.6%)

Gastrointestinal stromal tumor

Accessory spleen Anemia Extrahepatic cholestasis Proteinuria

Autosomal dominant inheritance Sporadic

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal (GI) tract, typically presenting in adults over the age of 40 (mean age 63), and only rarely in children, in various regions of the GI tract, most commonly the stomach or small intestine but also less commonly in the esophagus, appendix, rectum and colon. GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass, blood in stool, and intestinal obstruction. GISTs can also be seen in familial syndromes such as Carney triad and neurofibromatosis type 1.

129
(73.5%)

Congenital dyserythropoietic anemia type IV

Anemia Hepatosplenomegaly Jaundice

Autosomal dominant inheritance

Congenital dyserythropoietic anemia type IV (CDA IV) is a newly discovered form of CDA (see this term) characterized by ineffective erythropoiesis and hemolysis that leads to severe anemia at birth.

130
(73.3%)

Schnitzler syndrome

Anemia Fever Splenomegaly Urticaria

Schnitzler syndrome is a rare, underdiagnosed disorder in adults characterized by recurrent febrile rash, bone and/or joint pain, enlarged lymph nodes, fatigue, a monoclonal IgM component, leukocytosis and systemic inflammatory response.

130
(73.3%)

Relapsing fever

Erythema Fever Hemolytic anemia Splenomegaly

Relapsing fever is an infection caused by bacteria of the genus Borrelia, excluding those responsible for Lyme disease (see this term) belonging to the Borrelia burgdorferi complex.

130
(73.3%)

Congenital erythropoietic porphyria

Cutaneous photosensitivity Hemolytic anemia Nonimmune hydrops fetalis Splenomegaly

Autosomal recessive inheritance

Congenital erythropoietic porphyria, or Günther disease, is a form of erythropoietic porphyria characterized by very severe and mutilating photodermatosis.

130
(73.3%)

Omenn syndrome

Anemia Edema Purpura Splenomegaly

Autosomal recessive inheritance

Omenn syndrome (OS) is an inflammatory condition characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency (SCID; see this term).

130
(73.3%)

Chédiak-Higashi syndrome

Anemia Bruising susceptibility Edema Splenomegaly

Autosomal recessive inheritance

Chédiak-Higashi syndrome (CHS) is a rare severe genetic disorder generally characterized by partial oculocutaneous albinism (OCA, see this term), severe immunodeficiency, mild bleeding, neurological dysfunction and lymphoproliferative disorder. A classic, early-onset form and an attenuated, later-onset form (Atypical CHS; see this term) have been described.

130
(73.3%)

Waldenström macroglobulinemia

Cutis marmorata Fever Normocytic anemia Splenomegaly

Autosomal dominant inheritance

Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoproliferative disorder characterized by the accumulation of monoclonal cells in the bone marrow and peripheral lymphoid tissues, and associated with the production of serum immunoglobulin M (IgM) monoclonal protein.

130
(73.3%)

Autosomal recessive malignant osteopetrosis

Abnormality of metabolism/homeostasis Anemia Bruising susceptibility Splenomegaly

Infantile malignant osteopetrosis is a rare congenital disorder of bone resorption characterised by generalised skeletal densification.

130
(73.3%)

Muckle-Wells syndrome

Anemia Proteinuria Splenomegaly Urticaria

Autosomal dominant inheritance

Muckle-Wells syndrome (MWS) is an intermediate form of cryopyrin-associated periodic syndrome (CAPS; see this term) and is characterized by recurrent fever (with malaise and chills), recurrent urticaria-like skin rash, sensorineural deafness, general signs of inflammation (eye redness, headaches, arthralgia/myalgia) and potentially life-threatening secondary amyloidosis (AA type).

130
(73.3%)

Systemic-onset juvenile idiopathic arthritis

Anemia Proteinuria Purpura Splenomegaly

Systemic-onset juvenile idiopathic arthritis is marked by the severity of the extra-articular manifestations (fever, cutaneous eruptions) and by an equal sex ratio.

130
(73.3%)

Felty syndrome

Anemia Proteinuria Splenomegaly Telangiectasia

Autosomal dominant inheritance

Felty syndrome (FS), also known as ''super rheumatoid'' disease, is a severe form of rheumatoid arthritis (RA), characterized by a triad of RA, splenomegaly and neutropenia, resulting in susceptibility to bacterial infections.

130
(73.3%)

Blau syndrome

Anemia Erythema Joint swelling Splenomegaly

Autosomal dominant inheritance

Blau syndrome (BS) is a rare systemic inflammatory disease characterized by early onset granulomatous arthritis, uveitis and skin rash. BS now refers to both the familial and sporadic (formerly early-onset sarcoidosis) form of the same disease. The proposed term pediatric granulomatous arthritis is currently questioned since it fails to represent the systemic nature of the disease.

130
(73.3%)

CINCA syndrome

Anemia Edema Purpura Splenomegaly

Autosomal dominant inheritance

Chronic Infantile Neurological, Cutaneous, and Articular (CINCA) syndrome is characterised by skin rash, joint involvement, chronic meningitis with granulocytes and, in some cases, sensorineural hearing loss and ocular signs.

130
(73.3%)

Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome

Autoimmune hemolytic anemia Hypocalcemia Splenomegaly Urticaria

X-linked recessive inheritance

Immunodysregulation - polyendocrinopathy - enteropathy - X-linked (IPEX) syndrome is a severe congenital systemic autoimmune disease characterized by refractory diarrhea, endocrinopathies, cutaneous involvement, and infections.

130
(73.3%)

Angioimmunoblastic T-cell lymphoma

Anemia Edema Purpura Splenomegaly

130
(73.3%)

Chronic myelomonocytic leukemia

Anemia Hematuria Purpura Splenomegaly

130
(73.3%)

Chikungunya

Anemia Edema Purpura Splenomegaly

A rare infectious disease characterized by acute onset of high fever associated with debilitating polyarthralgia and usually accompanied by an erythematous skin rash (that may progress to vesiculobullous lesions in children) caused by the mosquitoe-borne Chikungunya virus. Myalgia, severe headache, and lymphadenopathy are frequently associated. Chronically the disease may cause recurrent, long-term polyarthralgia, arthritis, fatigue, and depression.

130
(73.3%)

Camurati-Engelmann disease

Abnormal subcutaneous fat tissue distribution Anemia Elevated erythrocyte sedimentation rate Splenomegaly

Autosomal dominant inheritance

Camurati-Englemann disease (CED) is a rare, clinically variable bone dysplasia syndrome characterized by hyperostosis of the long bones, skull, spine and pelvis, associated with severe pain in the extremities, a wide-based waddling gait, joint contractures, muscle weakness and easy fatigability. Camurati-Englemann disease (CED) is a rare, clinically variable bone dysplasia syndrome characterized by hyperostosis of the long bones, skull, spine and pelvis, associated with severe pain in the extremities, a wide-based waddling gait, joint contractures, muscle weakness and easy fatigability.

130
(73.3%)

American trypanosomiasis

Anemia Edema Erythema Splenomegaly

A tropical disease mainly found in latin America and transmitted by triatomine insects (mostly Triatoma infestans and Rhodnius prolixus and Panstrongylus megistus) harboring the hemoflagellate protozoan parasite Trypanosoma cruzi. The disease is characterized by an acute phase which is either asymptomatic or manifest with fever, inflammation at the inoculation site (inoculation chancre or chagoma), unilateral palpebral edema called the Romaña sign (when the triatomine bite occurs near the eye), enlarged lymph nodes, and splenomegaly. The chronic phase is lifelong and development of chagasic cardiomyopathy (30%; complex arrhythmias, heart failure, and thromboembolic events), digestive (10%; megaoesophagus and megacolon), neurological (10%; stroke, peripheral neuropathy and autonomic dysfunction), or mixed alterations (10%) may be observed. These can all lead to high morbidity and mortality rates.

130
(73.3%)

B-cell chronic lymphocytic leukemia

Anemia Proteinuria Purpura Splenomegaly

Autosomal dominant inheritance Multifactorial inheritance Somatic mutation Autosomal dominant somatic cell mutation

B-cell chronic lymphocytic leukemia (B-CLL) is a type of B-cell non-Hodgkin lymphoma (see this term), and the most common form of leukemia in Western countries, affecting elderly adults (mean age of 67 and 72 years) with a slight male predominance (1.7:1), and characterized by a highly variable clinical presentation that can include asymptomatic disease or non-specific B-symptoms such as unintentional weight loss, severe fatigue, fever (without evidence of infection), and night sweats as well as cervical lymphadenopathy, splenomegaly and frequent infections. Some patients can also develop autoimmune complications such as autoimmune hemolytic anemia or immune thrombocytopenia (see these terms). The clinical course is extremely heterogeneous with survival ranging from a few months to several decades.

130
(73.3%)

Wiskott-Aldrich syndrome

Edema Hemolytic anemia Petechiae Splenomegaly

Autosomal dominant inheritance Autosomal recessive inheritance X-linked recessive inheritance

A primary immunodeficiency disease characterized by microthrombocytopenia, eczema, infections and an increased risk for autoimmune manifestations and malignancies.

130
(73.3%)

Kikuchi-Fujimoto disease

Anemia Edema Purpura Splenomegaly

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder, characterized by regional cervical lymphadenopathy with tenderness, usually accompanied with mild fever and night sweats. Less frequent symptoms include weight loss, nausea, vomiting, sore throat.

130
(73.3%)

Cryoglobulinemic vasculitis

Cutis marmorata Hemolytic anemia Proteinuria Splenomegaly

Autosomal dominant inheritance

Mixed cryoglobulinemia (MC) is a rare multisystem disease characterized by the presence of circulating cryoprecipitable immune complexes in the serum, manifested clinically by a classical triad of purpura, weakness and arthralgia.

130
(73.3%)

Mantle cell lymphoma

Anemia Hematuria Purpura Splenomegaly

Mantle cell lymphoma is a rare form of malignant non-Hodgkin lymphoma (see this term) affecting B lymphocytes in the lymph nodes in a region called the ``mantle zone''.

130
(73.3%)

Essential thrombocythemia

Hemolytic anemia Proteinuria Purpura Splenomegaly

Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN, see this term) characterized by a sustained elevation of platelet number (> 450 x 109/L) with a tendency for thrombosis and hemorrhage.

130
(73.3%)

Fabry disease

Anemia Conjunctival telangiectasia Proteinuria Splenomegaly

X-linked inheritance X-linked recessive inheritance

Fabry disease (FD) is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.

130
(73.3%)

Lyme disease

Diabetes mellitus Hemolytic anemia Purpura Splenomegaly

Lyme disease (named after the towns in the USA where the disease was first identified) is a bacterial infection caused by Borrelia burgdorferi.

156
(72.8%)

3-hydroxy-3-methylglutaric aciduria

Anemia Hepatomegaly Jaundice Methylmalonic acidemia

Autosomal recessive inheritance

3-hydroxy-3-methylglutaric aciduria (3HMG) is an organic aciduria, due to deficiency of 3-hydroxy-3-methylglutaryl-CoA-lyase (a key enzyme in ketogenesis and leucine metabolism) usually presenting in infancy with episodes of metabolic decompensation triggered by periods of fasting or infections, which when left untreated are life-threatening and may lead to neurological sequelae.

157
(72.8%)

Primary biliary cholangitis

Hemolytic anemia Hepatomegaly Jaundice Low levels of vitamin D

Primary biliary cholangitis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure.

158
(72.6%)

Neuroendocrine tumor of stomach

Dermatological manifestations of systemic disorders Hepatomegaly Iron deficiency anemia

Gastric neuroendocrine tumor is a rare subtype of neuroendocrine neoplasm, arising from enterochromaffin-like cells in the stomach, with a variable clinical presentation, disease course and prognosis, depending on the disease type and histological grade. Most patients are asymptomatic, with diagnosis usually occurring incidentally during gastroscopy, however, symptoms of dyspepsia, anemia, pain, weight loss and gastrointestinal bleeding can be observed. Association with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I has been reported.

159
(72.4%)

Acromegaly

Diabetes mellitus Erythroid hyperplasia Splenomegaly Subcutaneous lipoma

An acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations.

160
(72.3%)

Pancreatoblastoma

Abdominal mass Anemia Elevated maternal serum alpha-fetoprotein Jaundice

A rare malignant epithelial pancreatic neoplasm, most often found in children, which usually presents with the non-specific symptoms of a palpable mass, vomiting abdominal pain, jaundice, and weight loss/failure to thrive, and is characterized histologically by multiple lines of differentiation (acinar, ductal, mesenchymal, neuroendocrine) and the presence of squamoid nests.