1
(90.1%)

hereditary spherocytosis type 4

Hemolytic anemia Hyperbilirubinemia Jaundice Spherocytosis Splenomegaly

Autosomal dominant inheritance

Any hereditary spherocytosis in which the cause of the disease is a mutation in the SLC4A1 gene.

1
(90.1%)

hereditary spherocytosis type 2

Hemolytic anemia Hyperbilirubinemia Jaundice Spherocytosis Splenomegaly

Autosomal dominant inheritance

Any hereditary spherocytosis in which the cause of the disease is a mutation in the SPTB gene.

1
(90.1%)

hereditary spherocytosis type 1

Hemolytic anemia Hyperbilirubinemia Jaundice Spherocytosis Splenomegaly

Autosomal dominant inheritance Autosomal recessive inheritance

Any hereditary spherocytosis in which the cause of the disease is a mutation in the ANK1 gene.

4
(87.7%)

overhydrated hereditary stomatocytosis

Hemolytic anemia Hyperbilirubinemia Jaundice Splenomegaly Stomatocytosis

Autosomal dominant inheritance

Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia.

4
(87.7%)

dehydrated hereditary stomatocytosis 2

Acanthocytosis Hemolytic anemia Hyperbilirubinemia Jaundice Splenomegaly

Autosomal dominant inheritance

Any dehydrated hereditary stomatocytosis in which the cause of the disease is a mutation in the KCNN4 gene.

4
(87.7%)

anemia, congenital dyserythropoietic, type 1a

Hydrops fetalis Macrocytic dyserythropoietic anemia Poikilocytosis Prolonged neonatal jaundice Splenomegaly

Autosomal recessive inheritance

4
(87.7%)

anemia, nonspherocytic hemolytic, due to G6PD deficiency

Fava bean-induced hemolytic anemia Fever Poikilocytosis Prolonged neonatal jaundice Splenomegaly

X-linked recessive inheritance X-linked dominant inheritance

8
(85.6%)

elliptocytosis 1

Elliptocytosis Hemolytic anemia Jaundice Splenomegaly

Autosomal dominant inheritance Autosomal recessive inheritance

Any hereditary elliptocytosis in which the cause of the disease is a mutation in the EPB41 gene.

8
(85.6%)

congenital dyserythropoietic anemia type type 1B

Anemia of inadequate production Jaundice Poikilocytosis Splenomegaly

Autosomal recessive inheritance

10
(82.9%)

lathosterolosis

Acanthocytosis Hepatosplenomegaly Hyperbilirubinemia Intrahepatic cholestasis

Autosomal recessive inheritance

Lathosterolosis is an extremely rare inborn error of sterol biosynthesis characterized by facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease.

11
(80.6%)

Bernard-Soulier syndrome, type A2, autosomal dominant

Hemolytic anemia Menorrhagia Petechiae Splenomegaly Stomatocytosis

Autosomal dominant inheritance

A Bernard-Soulier syndrome characterized by autosomal dominant inheritance of mild to moderate bleeding tendency, thrombocytopenia, and an increased mean platelet size that has material basis in heterozygous mutations in the GP1BA gene on chromosome 17p.

12
(80.2%)

cystic fibrosis-gastritis-megaloblastic anemia syndrome

Biliary cirrhosis Exocrine pancreatic insufficiency Megaloblastic anemia Reduced blood folate concentration

Autosomal recessive inheritance

A rare genetic disease reported in two siblings of consanguineous Arab parents and is characterized by cystic fibrosis, gastritis associated with Helicobacter pylori, folate deficiency megaloblastic anemia, and intellectual disability. There have been no further descriptions in the literature since 1991.

13
(80.2%)

severe congenital hypochromic anemia with ringed sideroblasts

Anemia Hepatomegaly Increased circulating ferritin concentration Poikilocytosis Splenomegaly

Autosomal dominant inheritance

STEAP3/TSAP6-related sideroblastic anemia is a very rare severe non-syndromic hypochromic anemia, which is characterized by transfusion-dependent hypochromic, poorly regenerative anemia, iron overload, resembling non-syndromic sideroblastic anemia except for increased erythrocyte protoporphyrin levels.

13
(80.2%)

sitosterolemia 1

Abnormality of the liver Episodic hemolytic anemia Hypercholesterolemia Splenomegaly Stomatocytosis

Autosomal recessive inheritance

15
(78.9%)

cryohydrocytosis

Abnormality of metabolism/homeostasis Hemolytic anemia Splenomegaly Stomatocytosis

Autosomal dominant inheritance

A rare, hereditary, hemolytic anemia due to a red cell membrane anomaly characterized by fatigue, mild anemia and pseudohyperkalemia due to a potassium leak from the red blood cells. A hallmark of this condition is that red blood cells lyse on storage at 4 degrees centigrade.

16
(78.4%)

anemia, nonspherocytic hemolytic, possibly due to defect in porphyrin metabolism

Elevated urinary delta-aminolevulinic acid Jaundice Nonspherocytic hemolytic anemia Splenomegaly

Autosomal recessive inheritance

16
(78.4%)

congenital dyserythropoietic anemia type 2

Anemia of inadequate production Endopolyploidy on chromosome studies of bone marrow Jaundice Reticulocytosis Splenomegaly

Autosomal recessive inheritance

Congenital dyserythropoietic anemia type II (CDA II) is the most common form of CDA characterized by anemia, jaundice and splenomegaly and often leading to liver iron overload and gallstones.

16
(78.4%)

hyperbilirubinemia, shunt, primary

Anemia of inadequate production Hyperbilirubinemia Jaundice Reticulocytosis Splenomegaly

Autosomal dominant inheritance

16
(78.4%)

hemolytic anemia due to diphosphoglycerate mutase deficiency

Abnormality of metabolism/homeostasis Jaundice Normochromic anemia Splenomegaly

Autosomal recessive inheritance

A rare, autosomal recessive, inherited disorder caused by mutation of the BPGM gene. It is characterized by hemolytic anemia and splenomegaly.

16
(78.4%)

dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

Exercise-induced hemolysis Increased circulating ferritin concentration Jaundice Reticulocytosis Splenomegaly

Autosomal dominant inheritance

16
(78.4%)

pyruvate kinase deficiency of red cells

Chronic hemolytic anemia Jaundice Nonimmune hydrops fetalis Reticulocytosis Splenomegaly

Autosomal recessive inheritance

Hemolytic anemia due to red cell pyruvate kinase (PK) deficiency is a metabolic disorder characterized by a variable degree of chronic nonspherocytic hemolytic anemia.

16
(78.4%)

non-spherocytic hemolytic anemia due to hexokinase deficiency

Abnormality of metabolism/homeostasis Jaundice Normochromic anemia Splenomegaly

Autosomal recessive inheritance

Nonspherocytic hemolytic anemia due to hexokinase deficiency (NSHA due to HK1 deficiency) is a very rare conditionmainly characterized by severe, chronic hemolysis, beginning in infancy. Approximately 20 cases of this condition have been described to date. Signs and symptoms of hexokinase deficiency are very similar to those of pyruvate kinase deficiency but anemia is generally more severe. Some affected individuals reportedly have had various abnormalities in addition to NSHA including multiple malformations, panmyelopathy, and latent diabetes.Itcan be caused by mutations in the HK1 gene and is inherited in an autosomal recessive manner. Treatment may include red cell transfusions for those with severe anemia.

16
(78.4%)

sideroblastic anemia 3

Anemia Conjugated hyperbilirubinemia Jaundice Splenomegaly

Autosomal recessive inheritance

16
(78.4%)

hemolytic anemia due to glucophosphate isomerase deficiency

Decreased glucosephosphate isomerase level Jaundice Nonspherocytic hemolytic anemia Splenomegaly

Autosomal recessive inheritance

Glucosephosphate isomerase (GPI) deficiency is an erythroenzymopathy characterized by chronic nonspherocytic hemolytic anemia.

16
(78.4%)

sickle cell anemia

Hematuria Hemolytic anemia Jaundice Splenomegaly

Autosomal recessive inheritance

Sickle cell anemias are chronic hemolytic diseases that may induce three types of acute accidents: severe anemia, severe bacterial infections, and ischemic vasoocclusive accidents (VOA) caused by sickle-shaped red blood cells obstructing small blood vessels and capillaries. Many diverse complications can occur.

16
(78.4%)

hereditary cryohydrocytosis with reduced stomatin

Hemolytic anemia Hyperkalemia Jaundice Splenomegaly

Autosomal dominant inheritance

16
(78.4%)

hereditary coproporphyria

Abnormality of metabolism/homeostasis Congenital hemolytic anemia Jaundice Splenomegaly

Autosomal dominant inheritance Autosomal recessive inheritance

Hereditary coproporphyria is a form of acute hepatic porphyria characterized by the occurrence of neuro-visceral attacks and, more rarely, by the presence of cutaneous lesions.

16
(78.4%)

prolidase deficiency

Abnormality of metabolism/homeostasis Anemia Prolonged neonatal jaundice Splenomegaly

Autosomal recessive inheritance

Prolidase deficiency is an inherited disorder of peptide metabolism characterized by severe skin lesions, recurrent infections (involving mainly the skin and respiratory system), dysmorphic facial features, variable cognitive impairment, and splenomegaly.

16
(78.4%)

familial hemophagocytic lymphohistiocytosis type 1

Anemia Hypertriglyceridemia Jaundice Splenomegaly

Autosomal recessive inheritance

Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome with an onset usually occurring within a few months or less common several years after birth.

16
(78.4%)

familial hemophagocytic lymphohistiocytosis 2

Anemia Hypertriglyceridemia Jaundice Splenomegaly

Autosomal recessive inheritance

Any genetic hemophagocytic lymphohistiocytosis in which the cause of the disease is a mutation in the PRF1 gene.

31
(77.5%)

celiac disease, susceptibility to, 1

Elevated hepatic transaminase Iron deficiency anemia Reduced blood folate concentration

Autosomal recessive inheritance Heterogeneous Multifactorial inheritance

32
(77.5%)

red cell phospholipid defect with hemolysis

Hyperbilirubinemia Intermittent jaundice Reticulocytosis Splenomegaly

Autosomal dominant inheritance

33
(76.8%)

thrombocytopenia, anemia, and myelofibrosis

Anemia Anisopoikilocytosis Splenomegaly

Autosomal recessive inheritance

34
(76.6%)

McLeod neuroacanthocytosis syndrome

Acanthocytosis Elevated serum creatine kinase Hepatosplenomegaly

X-linked inheritance

McLeod neuroacanthocytosis syndrome (MLS) is a form of neuroacanthocytosis and is characterized clinically by a Huntington's disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, and biochemically by absence of the Kx antigen and by weak expression of the Kell antigens.

35
(76.3%)

congenital bile acid synthesis defect 5

Iron deficiency anemia Jaundice Splenomegaly

Autosomal recessive inheritance

Any congenital bile acid synthesis defect in which the cause of the disease is a mutation in the ABCD3 gene.

35
(76.3%)

glycogen storage disease due to aldolase A deficiency

Epicanthus Jaundice Normochromic anemia Splenomegaly

Autosomal recessive inheritance

Glycogen storage disease due to aldolase A deficiency is an extremely rare glycogen storage disease characterized by hemolytic anemia with or without myopathy or intellectual deficit. Myopathy can be severe enough to result in fatal rhabdomyolysis in some patients. A family with episodic rhabdomyolysis (triggerd by fever) without hemolytic anemia has recently been reported.

35
(76.3%)

pancreatic insufficiency-anemia-hyperostosis syndrome

Anemia Carious teeth Jaundice Splenomegaly

Autosomal recessive inheritance

This syndrome is characterized by exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis.

35
(76.3%)

triosephosphate isomerase deficiency

Jaundice Normochromic anemia Optic disc pallor Splenomegaly

Autosomal recessive inheritance

Triosephosphate isomerase (TPI) deficiency is a severe autosomal recessive inherited multisystem disorder of glycolytic metabolism characterized by hemolytic anemia and neurodegeneration.

35
(76.3%)

Niemann-Pick disease type A

Microcytic anemia Osteoporosis Prolonged neonatal jaundice Splenomegaly

Autosomal recessive inheritance

Niemann-Pick disease type A is a very severe subtype of Niemann-Pick disease, an autosomal recessive lysosomal disease, and is characterized clinically by onset in infancy or early childhood with failure to thrive, hepatosplenomegaly, and rapidly progressive neurodegenerative disorders.

35
(76.3%)

Chediak-Higashi syndrome

Anemia Gingivitis Jaundice Splenomegaly

Autosomal recessive inheritance

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

41
(76.2%)

Rh deficiency syndrome

Hemolytic anemia Jaundice Stomatocytosis Unconjugated hyperbilirubinemia

Autosomal dominant inheritance

The Rh deficiency syndrome, also known as Rh-null syndrome, is a blood disorder where people have red blood cells (RBCs) lacking all Rh antigens. The Rh antigens maintain the integrity of the RBC membrane and therefore, RBCs which lack Rh antigens have an abnormal shape. There are two types of Rh deficiency syndrome: The regulator type is associated with many different changes (mutations) in the RHAG gene. The amorph type is caused by inactive copies of a gene (silent alleles) at the RH locus. As a result, the RBCs do not express any of the Rh antigens. The absence of the Rh complex alters the RBC shape, increases its tendency to break down (osmotic fragility), and shortens its lifespan, resulting in a hemolytic anemia that is usually mild. These patients are at risk of having adverse transfusion reactions because they may produce antibodies against several of the Rh antigens and can only receive blood from people who have the same condition. Rh deficiency syndrome is inherited in an autosomal recessive manner. Management is individualized according to the severity of hemolytic anemia.

41
(76.2%)

congenital thrombotic thrombocytopenic purpura

Jaundice Microangiopathic hemolytic anemia Proteinuria Schistocytosis

Autosomal recessive inheritance

Congenital thrombotic thrombocytopenic purpura is the hereditary form of thrombotic thrombocytopenic purpura (TTP) characterized by profound peripheral thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and single or multiple organ failure of variable severity.

43
(75.6%)

letterer-Siwe disease

Anemia Fever Hepatosplenomegaly Jaundice

Autosomal recessive inheritance

A multifocal, multisystem form of Langerhans-cell histiocytosis. There is involvement of multiple organ systems including the bones, skin, liver, spleen, and lymph nodes. Patients are usually infants presenting with fever, hepatosplenomegaly, lymphadenopathy, bone and skin lesions, and pancytopenia.

44
(75.3%)

fibrosis, neurodegeneration, and cerebral angiomatosis

Chronic hemolytic anemia Hepatomegaly Poikilocytosis Strabismus

Autosomal recessive inheritance

45
(74.6%)

cutaneous porphyria

Cholelithiasis Hemolytic anemia Pink urine Splenomegaly

Autosomal recessive inheritance

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

46
(74.5%)

primary familial polycythemia due to EPO receptor mutation

Hypertension Increased red blood cell mass Plethora Splenomegaly

Autosomal dominant inheritance

Primary familial polycythemia is an inherited hematological disorder resulting from mutations in the erythropoietin (EPO) receptor and is characterized by an elevated absolute red blood cell mass caused by uncontrolled red blood cell production in the presence of low EPO levels.

47
(73.5%)

COG6-CGD

Anemia Cholestasis Splenomegaly Type II transferrin isoform profile

Autosomal recessive inheritance

48
(73.5%)

reticuloendotheliosis, X-linked

Anemia Hepatosplenomegaly Jaundice

X-linked inheritance

48
(73.5%)

cyanosis, transient neonatal

Anemia Hepatomegaly Jaundice

Autosomal dominant inheritance

48
(73.5%)

constitutional megaloblastic anemia with severe neurologic disease

Hepatomegaly Jaundice Megaloblastic anemia

Autosomal recessive inheritance

51
(73.3%)

autoimmune lymphoproliferative syndrome type 1

Autoimmune hemolytic anemia Decreased lymphocyte apoptosis Splenomegaly Urticaria

Autosomal dominant inheritance

51
(73.3%)

autoimmune lymphoproliferative syndrome type 2A

Autoimmune hemolytic anemia Decreased lymphocyte apoptosis Splenomegaly Urticaria

Autosomal dominant inheritance

A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but incomplete penetrance. It is caused by a mutation in the CASP10 (caspase-10) gene that leads to defective Fas-induced apoptosis. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.

51
(73.3%)

Gaucher disease perinatal lethal

Anemia Nonimmune hydrops fetalis Petechiae Splenomegaly

Autosomal recessive inheritance

Fetal Gaucher disease is the perinatal lethal form of Gaucher disease (GD).

51
(73.3%)

vasculitis due to ADA2 deficiency

Anemia Cutis marmorata Fever Splenomegaly

Autosomal recessive inheritance

Vasculitis due to ADA2 deficiency is a rare, genetic, systemic and rheumatologic disease due to adenosine deaminase-2 inactivating mutations, combining variable features of autoinflammation, vasculitis, and a mild immunodeficiency. Variable clinical presentation includes chronic or recurrent systemic inflammation with fever, livedo reticularis or racemosa, early-onset ischemic or hemorrhagic strokes, peripheral neuropathy, abdominal pain, hepatosplenomegaly, portal hypertension, cutaneous polyarteritis nodosa, variable cytopenia and immunoglobulin deficiency.

51
(73.3%)

proteasome-associated autoinflammatory syndrome 1

Anemia Erythema Hypertriglyceridemia Splenomegaly

Autosomal recessive inheritance

56
(72.3%)

short-rib thoracic dysplasia 9 with or without polydactyly

Anemia Cholestasis Hepatomegaly Nephronophthisis

Autosomal recessive inheritance

An asphyxiating thoracic dystrophy that has material basis in homozygous or compound heterozygous mutation in the IFT140 gene on chromosome 16p13.

57
(71.5%)

ALG8-CDG

Abnormal isoelectric focusing of serum transferrin Anemia Cholestasis Hepatomegaly

Autosomal recessive inheritance

A form of congenital disorders of N-linked glycosylation that is characterized by gastrointestinal symptoms (diarrhea, vomiting, feeding problems with failure to thrive, protein-losing enteropathy), edema and ascites (including hydrops fetalis), hepatomegaly, renal tubulopathy, coagulation anomalies due to thrombocytopenia, brain involvement (psychomotor delay, seizures, ataxia), facial dysmorphism (low-set ears and retrognathia), pes equinovarus, and muscular hypotonia. Cataracts may also be observed. Prognosis is usually poor. The disease is caused by loss-of-function mutations in the gene ALG8 (11q14.1), resulting in a block in the initial step of protein glycosylation.

58
(71.2%)

beta-thalassemia-X-linked thrombocytopenia syndrome

Epistaxis Hemolytic anemia Petechiae Splenomegaly

X-linked recessive inheritance

Beta-thalassemia - X-linked thrombocytopenia is a form of beta-thalassemia characterized by splenomegaly and petechiae, moderate thrombocytopenia, prolonged bleeding time due to platelet dysfunction, reticulocytosis and mild beta-thalassemia.

58
(71.2%)

leukocyte adhesion deficiency 3

Anemia Epistaxis Petechiae Splenomegaly

Autosomal recessive inheritance

Leukocyte adhesion deficiency type III (LAD-III) is a form of LAD characterized by both severe bacterial infections and a severe bleeding disorder.

58
(71.2%)

transaldolase deficiency

Anemia Splenomegaly Telangiectasia Wide mouth

Autosomal recessive inheritance

Transaldolase deficiency is an inborn error of the pentose phosphate pathway that presents in the neonatal or antenatal period with hydrops fetalis, hepatosplenomegaly, hepatic dysfunction, thrombocytopenia, anemia, and renal and cardiac abnormalities.

61
(71.0%)

autoimmune polyendocrine syndrome type 1

Anemia Asplenia Cholelithiasis Diabetes mellitus

Autosomal dominant inheritance Autosomal recessive inheritance

Autoimmune polyendocrinopathy type 1, or APECED syndrome, is a genetic disease that manifests in childhood or early adolescence with a combination of chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune adrenal failure.

62
(70.9%)

hemochromatosis type 2B

Anemia Cirrhosis Increased circulating ferritin concentration Splenomegaly

Autosomal recessive inheritance

Any hemochromatosis type 2 in which the cause of the disease is a mutation in the HAMP gene.

62
(70.9%)

congenital dyserythropoietic anemia type 4

Anemia of inadequate production Hepatomegaly Hydrops fetalis Reticulocytosis Splenomegaly

Autosomal dominant inheritance

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

62
(70.9%)

congenital neutropenia-myelofibrosis-nephromegaly syndrome

Anemia Hepatomegaly Increased circulating antibody level Splenomegaly

Autosomal recessive inheritance

62
(70.9%)

autoimmune lymphoproliferative syndrome type 4

Decreased lymphocyte apoptosis Hemolytic anemia Hepatomegaly Splenomegaly

Autosomal dominant inheritance Somatic mutation

RAS-associated autoimmune leukoproliferative disease (RALD) is a rare genetic disorder characterized by monocytosis, autoimmune cytopenias, lymphoproliferation, hepatosplenomegaly, and hypergammaglobulinemia.

62
(70.9%)

Omenn syndrome

Anemia Hepatomegaly Hypoproteinemia 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).

62
(70.9%)

familial hemophagocytic lymphohistiocytosis 4

Anemia Fever Hepatomegaly Splenomegaly

Autosomal recessive inheritance

Any genetic hemophagocytic lymphohistiocytosis in which the cause of the disease is a mutation in the STX11 gene.

62
(70.9%)

autosomal recessive osteopetrosis 7

Anemia Hepatomegaly Hypocalcemic seizures Splenomegaly

Autosomal recessive inheritance

Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the TNFRS11A gene.

62
(70.9%)

immunodeficiency 27A

Anemia Fever Hepatosplenomegaly Splenomegaly

Autosomal recessive inheritance

62
(70.9%)

neonatal severe primary hyperparathyroidism

Anemia Hepatomegaly Hypophosphatemia Splenomegaly

Autosomal dominant inheritance Autosomal recessive inheritance

Neonatal severe primary hyperparathyroidism (NSHPT) is characterized by severe hypercalcemia (> 3.5 mM) from birth and associated with major hyperparathyroidism.

62
(70.9%)

autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency

Autoimmune hemolytic anemia Decreased circulating antibody level Hepatomegaly Splenomegaly

Autosomal dominant inheritance

A somatic mutation in the CTLA4 gene resulting in only a single functional gene. Haploinsufficiency for CTLA4 is associated with autoimmune lymphoproliferative syndrome, type V.

62
(70.9%)

proteasome-associated autoinflammatory syndrome 3

Anemia Hepatomegaly Recurrent fever Splenomegaly

Autosomal recessive inheritance

62
(70.9%)

X-linked lymphoproliferative disease due to SH2D1A deficiency

Anemia Hepatomegaly Increased circulating IgM level Splenomegaly

X-linked recessive inheritance

A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked SH2D1A gene, resulting in B cell lymphoproliferation and manifesting with various phenotypes which include EBV-driven severe or fulminant mononucleosis, hemophagocytic lymphohistiocytosis (presenting with fulminant hepatitis, hepatic necrosis, bone marrow hypoplasia, and neurological involvement), hypogammaglobulinemia, and B-cell lymphoma. Additional variable manifestations include vasculitis, lymphomatoid granulomatosis, aplastic anemia, and chronic gastritis. Occasionally, T-cell lymphoma may be observed. Laboratory findings include normal or increased activated T cells and reduced memory B cells.

62
(70.9%)

lymphoproliferative syndrome 1

Anemia Elevated erythrocyte sedimentation rate Hepatomegaly Splenomegaly

Autosomal recessive inheritance

A condition of decreased or absent presence or activity of IL2-inducible t-cell kinase. Deficiency of this protein is associated with lymphoproliferative syndrome 1, an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia..

62
(70.9%)

autosomal recessive osteopetrosis 1

Anemia Elevated alkaline phosphatase Hepatomegaly Splenomegaly

Autosomal recessive inheritance Heterogeneous

Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the TCIRG1 gene.

62
(70.9%)

hyper-IgM syndrome type 1

Decreased circulating IgA level Hemolytic anemia Hepatomegaly Splenomegaly

X-linked recessive inheritance

Hyper IgM Syndrome Type 1 (HIGM-1) is the X-linked variant of the Hyper-IgM syndrome. The affected individuals are virtually always male, because males only have one X chromosome, received from their mothers. Their mothers are not symptomatic, even though they are carriers of the allele, because the trait is recessive. Male offspring of these women have a 50% chance of inheriting their mother's mutant allele.

62
(70.9%)

adenosine deaminase deficiency

Autoimmune hemolytic anemia Decreased circulating IgA level Hepatomegaly Splenomegaly

Autosomal recessive inheritance Somatic mosaicism

Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is a form of SCID characterized by profound lymphopenia and very low immunoglobulin levels of all isotypes resulting in severe and recurrent opportunistic infections.

62
(70.9%)

immunodeficiency due to CD25 deficiency

Autoimmune hemolytic anemia Diabetes mellitus Hepatosplenomegaly Splenomegaly

Autosomal recessive inheritance

62
(70.9%)

lysinuric protein intolerance

Anemia Hepatomegaly Hyperammonemia Splenomegaly

Autosomal recessive inheritance

Lysinuric protein intolerance (LPI) is a very rare inherited multisystem condition caused by distrubance in amino acid metabolism.

62
(70.9%)

autosomal recessive osteopetrosis 5

Anemia Hepatomegaly Hypocalcemia Splenomegaly

Autosomal recessive inheritance

Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the OSTM1 gene.

62
(70.9%)

mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders

Anemia Macrovesicular hepatic steatosis Proteinuria Splenomegaly

Autosomal recessive inheritance

62
(70.9%)

mevalonic aciduria

Edema Elevated hepatic transaminase Fluctuating splenomegaly Normocytic hypoplastic anemia

Autosomal recessive inheritance

Mevalonic aciduria (MVA) is a rare, very severe form of mevalonate kinase deficiency (MKD) characterized by dysmorphic features, failure to thrive, psychomotor delay, ocular involvement, hypotonia, progressive ataxia, myopathy, and recurrent inflammatory episodes.

83
(70.8%)

autoinflammation with arthritis and dyskeratosis

Autoimmune hemolytic anemia Dry skin Increased circulating IgA level Splenomegaly

Autosomal dominant inheritance Autosomal recessive inheritance

84
(69.7%)

MIRAGE syndrome

Anemia Hypoglycemia Hypoplastic spleen Petechiae

Autosomal dominant inheritance

An autosomal dominant condition caused by mutation(s) in the SAMD9 gene, encoding sterile alpha motif domain-containing protein 9A. It is a syndromic condition comprising myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital abnormalities, and enteropathy.

85
(69.6%)

trimethylaminuria (disease)

Anemia Splenomegaly Trimethylaminuria

Autosomal recessive inheritance

85
(69.6%)

severe combined immunodeficiency due to LAT deficiency

Decreased circulating antibody level Hemolytic anemia Splenomegaly

Autosomal recessive inheritance

85
(69.6%)

purine nucleoside phosphorylase deficiency

Autoimmune hemolytic anemia Hypouricemia Splenomegaly

Autosomal recessive inheritance

Purine nucleoside phosphorylase (PNP) deficiency is a disorder of purine metabolism characterized by progressive immunodeficiency leading to recurrent and opportunistic infections, autoimmunity and malignancy as well as neurologic manifestations.

88
(69.3%)

hemolytic uremic syndrome, atypical, susceptibility to, 1

Fever Microangiopathic hemolytic anemia Purpura Schistocytosis

Autosomal dominant inheritance Autosomal recessive inheritance

89
(68.7%)

hemoglobin H disease

Hemolytic anemia Hepatomegaly Splenomegaly

Hemoglobin H (HbH) disease is a moderate to severe form of alpha-thalassemia characterized by pronounced microcytic hypochromic hemolytic anemia.

89
(68.7%)

osteopetrosis, autosomal dominant 3

Anemia Hepatomegaly Osteopenia Splenomegaly

Autosomal dominant inheritance

89
(68.7%)

autosomal recessive osteopetrosis 8

Anemia Hepatomegaly Macrocephaly Splenomegaly

Autosomal recessive inheritance

Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the SNX10 gene.

89
(68.7%)

autosomal recessive osteopetrosis 4

Anemia Hepatosplenomegaly Splenomegaly Visual impairment

Autosomal recessive inheritance

Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the CLCN7 gene.

89
(68.7%)

Gaucher disease type I

Anemia Epistaxis Hepatomegaly Splenomegaly

Autosomal recessive inheritance

Gaucher disease type 1 is the chronic non-neurological form of Gaucher disease (GD) characterized by organomegaly, bone involvement and cytopenia.

89
(68.7%)

Gaucher disease type II

Anemia Hepatomegaly Splenomegaly Trismus

Autosomal recessive inheritance

Gaucher disease type 2 is the acute neurological form of Gaucher disease (GD). It is characterized by early-onset and severe neurological involvement of the brainstem, associated with an organomegaly and generally leading to death before the age of 2.

89
(68.7%)

autoimmune lymphoproliferative syndrome type 3

Hemolytic anemia Hepatomegaly Nephrotic syndrome Splenomegaly

Autosomal recessive inheritance

A rare, primary immunodeficiency. It is caused by a currently undetermined defect in the Fas-induced apoptosis pathway. No mutations in Fas, FASLG or CASP10 are detectable. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.

89
(68.7%)

autosomal recessive severe congenital neutropenia due to G6PC3 deficiency

Anemia Cryptorchidism Hepatomegaly Splenomegaly

Autosomal recessive inheritance

97
(68.1%)

heme oxygenase 1 deficiency

Hemolytic anemia Hepatomegaly Proteinuria

Autosomal recessive inheritance

97
(68.1%)

thanatophoric dysplasia, Glasgow variant

Abnormality of metabolism/homeostasis Anemia Hepatosplenomegaly

Autosomal recessive inheritance

97
(68.1%)

familial hemophagocytic lymphohistiocytosis 3

Anemia Fever Hepatosplenomegaly

Autosomal recessive inheritance

Any genetic hemophagocytic lymphohistiocytosis in which the cause of the disease is a mutation in the UNC13D gene.

97
(68.1%)

renal tubular acidosis, distal, 4, with hemolytic anemia

Hemolytic anemia Hepatosplenomegaly Metabolic acidosis

Autosomal dominant inheritance Autosomal recessive inheritance

Distal renal tubular acidosis (dRTA) with anemia is a very rare form of distal renal tubular acidosis (dRTA) characterized by a defect in renal acidification and hereditary hemolytic anemia.