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.

97
(68.1%)

autosomal recessive osteopetrosis 3

Anemia Elevated serum acid phosphatase Hepatosplenomegaly

Autosomal recessive inheritance

Osteopetrosis with renal tubular acidosis is a rare disorder characterized by osteopetrosis, renal tubular acidosis (RTA), and neurological disorders related to cerebral calcifications.

97
(68.1%)

classic galactosemia

Cirrhosis Hemolytic anemia Hepatomegaly Metabolic acidosis

Autosomal recessive inheritance

Classic galactosemia is a life-threatening metabolic disease with onset in the neonatal period. Infants usually develop feeding difficulties, lethargy, and severe liver disease.

97
(68.1%)

myopathy, lactic acidosis, and sideroblastic anemia 2

Hepatomegaly Increased serum lactate Sideroblastic anemia

Autosomal recessive inheritance

Any mitochondrial myopathy and sideroblastic anemia in which the cause of the disease is a mutation in the YARS2 gene.

97
(68.1%)

severe early-onset pulmonary alveolar proteinosis due to MARS deficiency

Acidosis Anemia Cirrhosis Hepatomegaly

Autosomal recessive inheritance

97
(68.1%)

infantile liver failure syndrome 1

Anemia Hepatic steatosis Hepatomegaly Lactic acidosis

Autosomal recessive inheritance

Any infantile liver failure in which the cause of the disease is a mutation in the LARS gene.

97
(68.1%)

protein-losing enteropathy (disease)

Hepatomegaly Hypoalbuminemia Iron deficiency anemia

Autosomal recessive inheritance

Pathological conditions in the intestines that are characterized by the gastrointestinal loss of serum proteins, including serum albumin; immunoglobulins; and at times lymphocytes. Severe condition can result in hypogammaglobulinemia or lymphopenia. Protein-losing enteropathies are associated with a number of diseases including intestinal lymphangiectasis; whipple'S disease; and neoplasms of the small intestine.

97
(68.1%)

3-hydroxy-3-methylglutaric aciduria

Anemia Hepatomegaly Metabolic acidosis

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.

97
(68.1%)

mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy

Hepatomegaly Increased serum lactate Microcytic anemia

Autosomal recessive inheritance

97
(68.1%)

Wilson disease

Cirrhosis Hemolytic anemia Hepatomegaly Proteinuria

Autosomal recessive inheritance

Wilson disease is a very rare inherited multisystemic disease presenting non-specific neurological, hepatic, psychiatric or osseo-muscular manifestations due to excessive copper deposition in the body.

97
(68.1%)

propionic acidemia

Anemia Hepatomegaly Metabolic acidosis

Autosomal recessive inheritance

Propionic acidemia (PA) is an organic aciduria caused by the deficient activity of the propionyl Coenzyme A carboxylase and is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and that may be complicated by cardiomyopathy.

97
(68.1%)

cytochrome-c oxidase deficiency disease

Anemia Hepatomegaly Proteinuria

Autosomal recessive inheritance Heterogeneous Mitochondrial inheritance

A very rare inherited metabolic disorder characterized by deficiency of the enzyme cytochrome-C oxidase. It may be manifested as an isolated myopathy or a systemic disorder. Signs and symptoms include myotonia, dysfunction of the heart, kidney, and brain, and lactic acidosis.

97
(68.1%)

autosomal dominant Aarskog syndrome

Cirrhosis Hepatomegaly Lymphedema Macrocytic anemia

X-linked inheritance Sex-limited autosomal dominant

97
(68.1%)

thrombocytopenia-absent radius syndrome

Anemia Decreased circulating antibody level Hepatosplenomegaly

Autosomal recessive inheritance

Thrombocytopenia-absent radius (TAR) syndrome is a very rare congenital malformation syndrome characterized by bilateral radial aplasia and thrombocytopenia.

114
(67.5%)

combined immunodeficiency due to OX40 deficiency

Coombs-positive hemolytic anemia Splenomegaly

Autosomal recessive inheritance

Combined immunodeficiency due to OX40 deficiency is a rare combined T and B cell immunodeficiency characterized by susceptibility to develop an aggressive, childhood-onset, disseminated, cutaneous and systemic Kaposi sarcoma.

115
(67.3%)

vitamin B12-responsive methylmalonic acidemia type cblB

Anemia Hepatomegaly Methylmalonic acidemia

Autosomal recessive inheritance

An autosomal recessive form of methylmalonic aciduria, caused by mutation(s) in the MMAB gene, encoding cob(I)yrinic acid a,c-diamide adenosyltransferase, mitochondrial.

115
(67.3%)

vitamin B12-responsive methylmalonic acidemia type cblA

Anemia Hepatomegaly Methylmalonic acidemia

Autosomal recessive inheritance

An autosomal recessive form of methylmalonic aciduria, caused by mutation(s) in the MMAA gene, encoding MMAA protein.

117
(67.3%)

autoimmune polyendocrinopathy type 2

Asplenia Cirrhosis Iron deficiency anemia Type II diabetes mellitus

Autosomal dominant inheritance Autosomal recessive inheritance Multifactorial inheritance

Autoimmune polyglandular syndrome of likely polygenic etiology characterized by the presence of primary adrenal insufficiency in association with autoimmune thyroiditis and/or type 1 diabetes mellitus; this condition is not associated with mucocutaneous candidiasis.

118
(67.2%)

cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome

Cirrhosis Hepatomegaly Hyperbilirubinemia Polycythemia

Autosomal recessive inheritance

119
(67.2%)

Stormorken syndrome

Anemia Asplenia Elevated serum creatine kinase Ichthyosis

Autosomal dominant inheritance

Stormorken-Sjaastad-Langslet syndrome is characterized by thrombocytopathy, asplenia, miosis, muscle fatigue, migraine, dyslexia, and ichthyosis. It has been described in six members of one family. It is transmitted as an autosomal dominant trait.

120
(67.2%)

thrombocytopenia, X-linked, with or without dyserythropoietic anemia

Acanthocytosis Anemia of inadequate production Epistaxis Petechiae

X-linked recessive inheritance

An X-linked condition caused by mutation(s) in the GATA1 gene, encoding erythroid transcription factor. It is characterized by thrombocytopenia, as well as abnormal platelet function and morphology. Dyserythropoietic anemia of variable severity may also be present.