121
(66.9%)

congenital dyserythropoietic anemia type 3

Hemosiderinuria Jaundice Macrocytic anemia

Autosomal dominant inheritance

Congenital dyserythropoietic anemia type III (CDA III) is a rare form of CDA characterized by dyserythropoiesis, with big multinucleated erythroblasts in the bone marrow, and manifesting with mild to moderate anemia.

121
(66.9%)

glycogen storage disease VII

Hemolytic anemia Hyperuricemia Jaundice

Autosomal recessive inheritance

Muscle phosphofructokinase (PFK) deficiency (Tarui's disease), or glycogen storage disease type 7 (GSD7), is a rare form of glycogen storage disease characterized by exertional fatigue and muscular exercise intolerance. It occurs in childhood.

123
(66.6%)

acquired polycythemia vera

Cerebral hemorrhage Increased red blood cell mass Splenomegaly

Autosomal dominant inheritance Somatic mutation Sporadic

Polycythemia vera (PV) is an acquired myeloproliferative disorder characterized by an elevated absolute red blood cell mass caused by uncontrolled red blood cell production, frequently associated with uncontrolled white blood cell and platelet production.

124
(66.2%)

STING-associated vasculopathy with onset in infancy

Anemia Cutis marmorata Fever Follicular hyperplasia

Autosomal dominant inheritance

STING-associated vasculopathy with onset in infancy (SAVI) is a rare, genetic autoinflammatory disorder, type I interferonopathy due to constitutive STING (STimulator of INterferon Genes) activation, characterized by neonatal or infantile onset systemic inflammation and small vessel vasculopathy resulting in severe skin, pulmonary and joint lesions. Patients present with intermittent low-grade fever, recurrent cough and failure to thrive, in association with progressive interstitial lung disease, polyarthritis and violaceous scaling lesions on fingers, toes, nose, cheeks, and ears (which are exacerbated by cold exposure) that often progress to chronic acral ulceration, necrosis and autoamputation.

125
(66.0%)

pyridoxine-responsive sideroblastic anemia

Hepatosplenomegaly Pyridoxine-responsive sideroblastic anemia

Autosomal recessive inheritance X-linked inheritance

125
(66.0%)

atypical Gaucher disease due to saposin C deficiency

Anemia Hepatosplenomegaly Osteopenia

Autosomal recessive inheritance

Any Gaucher disease in which the cause of the disease is a mutation in the PSAP gene.

125
(66.0%)

lethal hemolytic anemia-genital anomalies syndrome

Hemolytic anemia Hepatosplenomegaly Hypospadias

Autosomal dominant inheritance

Waters-West syndrome is characterized by the association of lethal non-spherocytic, non-immune hemolytic anemia with abnormalities of the external genitalia (micropenis and hypospadias), flat occiput, dimpled earlobes, deep plantar creases, and increased space between the first and second toes. It has been described only once in two brothers who died a few hours after birth. The second-born infant had massive ascites and hepatosplenomegaly. The mother had two spontaneous abortions (at 6 and 12 weeks gestation) but gave birth to a normal girl, suggesting an autosomal or X-linked recessive mode of inheritance. Although the parents were not known to be consanguineous, they shared a French-Canadian and American Indian ethnic origin.

125
(66.0%)

autosomal recessive osteopetrosis 2

Anemia Hepatosplenomegaly Mandibular prognathia

Autosomal recessive inheritance

Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the TNFSF11 gene.

125
(66.0%)

Shwachman-Diamond syndrome 2

Hepatomegaly High palate Normocytic anemia

Autosomal recessive inheritance

Shwachman-Diamond syndrome-2 (SDS2) is characterized by exocrine pancreatic dysfunction, hematopoietic abnormalities, short stature, and metaphyseal dysplasia ({1:Stepensky et al., 2017}).nnFor a discussion of genetic heterogeneity of Shwachman-Diamond syndrome, see SDS1 (OMIM:260400).

125
(66.0%)

Shwachman-Diamond syndrome 1

Anemia Hepatomegaly Nephrocalcinosis

Autosomal recessive inheritance

131
(64.8%)

fumaric aciduria

Cholestasis Metabolic acidosis Polycythemia

Autosomal recessive inheritance

Fumaric aciduria (FA), an autosomal recessive metabolic disorder, is most often characterized by early onset but non-specific clinical signs: hypotonia, severe psychomotor impairment, convulsions, respiratory distress, feeding difficulties and frequent cerebral malformations, along with a distinctive facies. Some patients present with only moderate intellectual impairment.

132
(64.8%)

X-linked congenital hemolytic anemia

Hemolytic anemia Jaundice

X-linked recessive inheritance

133
(64.7%)

neuroblastoma, susceptibility to

Abdominal mass Anemia Fever Skin nodule

Autosomal dominant inheritance Heterogeneous Somatic mutation Sporadic

134
(63.8%)

telangiectasia, hereditary hemorrhagic, type 2

Anemia Cirrhosis Cyanosis Lip telangiectasia Polycythemia

Autosomal dominant inheritance Heterogeneous

Any hereditary hemorrhagic telangiectasia in which the cause of the disease is a mutation in the ACVRL1 gene.

134
(63.8%)

telangiectasia, hereditary hemorrhagic, type 1

Anemia Cirrhosis Cyanosis Lip telangiectasia Polycythemia

Autosomal dominant inheritance

136
(63.4%)

congenital bile acid synthesis defect 2

Abnormality of the coagulation cascade Hyperbilirubinemia Jaundice Splenomegaly

Autosomal recessive inheritance

Congenital bile acid synthesis defect type 2 (BAS defect type 2) is an anomaly of bile acid synthesis characterized by severe and rapidly progressive cholestatic liver disease, and malabsorption of fat and fat-soluble vitamins.

136
(63.4%)

immunodeficiency 47

Decreased circulating antibody level Leukopenia Prolonged neonatal jaundice Splenomegaly

X-linked recessive inheritance

Any primary immunodeficiency disease in which the cause of the disease is a mutation in the ATP6AP1 gene.

136
(63.4%)

Reynolds syndrome

Gastrointestinal hemorrhage Hyperbilirubinemia Jaundice Splenomegaly

Autosomal dominant inheritance

Reynolds syndrome (RS) is an autoimmune disorder characterized by the association of primary biliary cirrhosis (PBC) with limited cutaneous systemic sclerosis (lcSSc).

136
(63.4%)

congenital bile acid synthesis defect 3

Abnormality of the coagulation cascade Elevated alkaline phosphatase Jaundice Splenomegaly

Autosomal recessive inheritance

Congenital bile acid synthesis defect type 3 (BAS defect type 3) is a severe anomaly of bile acid synthesis characterized by severe neonatal cholestatic liver disease.

136
(63.4%)

congenital bile acid synthesis defect 1

Abnormality of the coagulation cascade Hyperbilirubinemia Jaundice Splenomegaly

Autosomal recessive inheritance

Congenital bile acid synthesis defect type 1 (BAS defect type 1) is the most common anomaly of bile acid synthesis characterized by variable manifestations of progressive cholestatic liver disease, and fat malabsorption.

136
(63.4%)

Niemann-Pick disease, type C1

Abnormal circulating cholesterol concentration Prolonged neonatal jaundice Sea-blue histiocytosis Splenomegaly

Autosomal recessive inheritance Heterogeneous

Type C Niemann-Pick disease associated with a mutation in the gene NPC1, encoding Niemann-Pick C1 protein.

136
(63.4%)

Niemann-Pick disease, type C2

Abnormal circulating cholesterol concentration Prolonged neonatal jaundice Sea-blue histiocytosis Splenomegaly

Autosomal recessive inheritance Heterogeneous

Niemann-Pick disease type C2 is a rare metabolic condition that affects many different parts of the body. Although signs and symptoms can develop at any age (infancy through adulthood), most affected people develop features of the condition during childhood. Neimann-Pick disease type C2 may be characterized by ataxia (difficulty coordinating movements), vertical supranuclear gaze palsy (inability to move the eyes vertically), poor muscle tone, hepatosplenomegaly (enlarged liver and spleen), interstitial lung disease, intellectual decline, seizures, speech problems, and difficulty swallowing. Niemann-Pick disease type C2 is caused by changes (mutations) in the NPC2 gene and is inherited in an autosomal recessive manner. There is, unfortunately, no cure for Niemann-Pick disease type C2. Treatment is based on the signs and symptoms present in each person.

136
(63.4%)

mitochondrial DNA depletion syndrome 3

Hypoglycemia Jaundice Splenomegaly Thrombocytopenia

Autosomal recessive inheritance

Any mitochondrial DNA depletion syndrome in which the cause of the disease is a mutation in the DGUOK gene.

136
(63.4%)

Aicardi-Goutieres syndrome 1

Fever Petechiae Prolonged neonatal jaundice Splenomegaly

Autosomal dominant inheritance Autosomal recessive inheritance

Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the TREX1 gene.

145
(63.1%)

X-linked erythropoietic protoporphyria

Cholelithiasis Increased erythrocyte protoporphyrin concentration Iron deficiency anemia

X-linked inheritance X-linked dominant inheritance

X-linked form of erythropoietic protoporphyria.

145
(63.1%)

protoporphyria, erythropoietic, 1

Cholelithiasis Edema Hemolytic anemia

Autosomal recessive inheritance

Erythropoietic protoporphyria caused by a compound heterozygous or homozygous mutation in the gene encoding ferrochelatase (FECH) on chromosome 18q21.

147
(62.9%)

pantothenate kinase-associated neurodegeneration

Acanthocytosis Dysphagia Hyperpigmentation of the skin Urinary incontinence

Autosomal recessive inheritance

Pantothenate kinase-associated neurodegeneration (PKAN) is the most common type of neurodegeneration with brain iron accumulation (NBIA), a rare neurodegenerative disorder characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation on the brain and axonal spheroids in the central nervous system.

148
(62.6%)

multiple intestinal atresia

Abnormal abdomen morphology Autoimmune hemolytic anemia Hypertelorism Interface hepatitis

Autosomal recessive inheritance

Multiple intestinal atresia is a rare form of intestinal atresia characterized by the presence of numerous atresic segments in the small bowel (duodenum) or large bowel and leading to symptoms of intestinal obstruction: vomiting, abdominal bloating and inability to pass meconium in newborns.

149
(62.4%)

short stature with microcephaly and distinctive facies

Anemia Anisopoikilocytosis Microcephaly Recurrent infections Spotty hyperpigmentation

Autosomal recessive inheritance

150
(62.2%)

immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome

Autoimmune hemolytic anemia Diabetes mellitus Eczema Lymphadenopathy

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.

151
(62.0%)

combined immunodeficiency due to STIM1 deficiency

Autoimmune hemolytic anemia Hypohidrosis Lymphadenopathy Recurrent fever

Autosomal recessive inheritance

Aform of combined immunodeficiency due to Calcium release activated Ca2+(CRAC) channel dysfunction characterized by recurrent infections, autoimmunity, congenital myopathy and ectodermal dysplasia.

152
(61.8%)

hemochromatosis type 3

Anemia Cirrhosis Increased circulating ferritin concentration Purpura

Autosomal recessive inheritance

Type 3 hemochromatosis is a form of rare hereditary hemochromatosis (HH), a group of diseases characterized by excessive tissue iron deposition of genetic origin.

153
(61.6%)

autosomal recessive congenital ichthyosis 5

Acanthocytosis Erythroderma Palmoplantar keratoderma

Autosomal recessive inheritance

An autosomal recessive congenital ichthyosis characterized by fine white or greyish-white scales, hyperkeratosis, moderate acanthosis, and moderate parakeratosis that has material basis in homozygous mutation in the CYP4F22 gene on chromosome 19p13.

154
(61.4%)

hereditary fructose intolerance

Fructose intolerance Gastrointestinal hemorrhage Hepatomegaly Jaundice

Autosomal recessive inheritance

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder of fructose metabolism, resulting from a deficiency of hepatic fructose-1-phosphate aldolase activity and leading to gastrointestinal disorders and postprandial hypoglycemia following fructose ingestion. HFI is a benign condition when treated, but it is life-threatening and potentially fatal if left untreated.

155
(61.3%)

pseudo-TORCH syndrome 1

Jaundice Petechiae Renal insufficiency Splenomegaly

Autosomal recessive inheritance

156
(61.1%)

Chuvash polycythemia

Hemangioma Increased red blood cell mass Plethora

Autosomal recessive inheritance

Chuvash erythrocytosis is a rare, genetic, congenital secondary polycythemia disorder characterized by increased hemoglobin, hematocrit and erythropoietin serum levels and normal oxygen affinity, which usually manifests with headache, dizziness, dyspnea and/or plethora. Patients present an increased risk of hemorrhage, thrombosis and early death.

157
(61.0%)

Wolman disease with hypolipoproteinemia and acanthocytosis

Acanthocytosis Hypolipoproteinemia Vomiting

Autosomal recessive inheritance

157
(61.0%)

abetalipoproteinemia

Abetalipoproteinemia Acanthocytosis Fat malabsorption

Autosomal recessive inheritance

Abetalipoproteinemia/ homozygous familial hypobetalipoproteinemia (ABL/HoFHBL) is a severe form of 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.

157
(61.0%)

hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration

Acanthocytosis Decreased LDL cholesterol concentration Dysphagia

Autosomal recessive inheritance

157
(61.0%)

chorea-acanthocytosis

Acanthocytosis Dysphagia Elevated serum creatine kinase

Autosomal recessive inheritance

Chorea-acanthocytosis (ChAc) is a form of neuroacanthocytosis and is characterized clinically by a Huntington disease-like phenotype with progressive neurological symptoms including movement disorders, psychiatric manifestations and cognitive disturbances.

161
(60.9%)

Peutz-Jeghers syndrome

Abnormality of the ureter Biliary tract abnormality Iron deficiency anemia

Autosomal dominant inheritance

Peutz-Jeghers syndrome (PJS) is an inherited gastrointestinal disorder characterized by development of characteristic hamartomatous polyps throughout the gastrointestinal (GI) tract, and by mucocutaneous pigmentation. PJS carries a considerably increased risk of GI and extra-GI malignancies.

162
(60.7%)

CCDC115-CDG

Abnormal glycosylation Long face Prolonged neonatal jaundice Splenomegaly

Autosomal recessive inheritance

163
(60.7%)

congenital bile acid synthesis defect 4

Abnormality of the coagulation cascade Hepatomegaly Hyperbilirubinemia Prolonged neonatal jaundice

Autosomal recessive inheritance

Congenital bile acid synthesis defect type 4 (BAS defect type 4) is an anomaly of bile acid synthesis characterized by mild cholestatic liver disease, fat malabsorption and/or neurological disease.

163
(60.7%)

acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

Abnormality of the coagulation cascade Hepatomegaly Increased serum lactate Jaundice

Autosomal recessive inheritance

Acute infantile liver failure due to mtDNA-encoded proteins synthesis defect is a very rare mitochondrial respiratory chain deficiency described in fewer than 10 infants, primarily of middle Eastern descent, and characterized clinically by transient but life-threatening liver failure with elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia, and lactic acidemia.

163
(60.7%)

trichohepatoenteric syndrome 1

Hepatomegaly Hypoalbuminemia Jaundice Thrombocytosis

Autosomal recessive inheritance

Any tricho-hepato-enteric syndrome in which the cause of the disease is a mutation in the TTC37 gene.

166
(60.5%)

SRD5A3-CDG

Elevated hepatic transaminase Microcytic anemia Type I transferrin isoform profile

Autosomal recessive inheritance

SRD5A3-CDG is a rare, non X-linked congenital disorder of gyclosylation due to steroid 5 alpha reductase type 3 deficiency characterized by a highly variable phenotype typically presenting with severe visual impairment, variable ocular anomalies (such as optic nerve hypoplasia/atrophy, iris and optic nerve coloboma, congenital cataract, glaucoma), intellectual disability, cerebellar abnormalities, nystagmus, hypotonia, ataxia, and/or ichthyosiform skin lesions. Other reported manifestations include retinitis pigmentosa, kyphosis, congenital heart defects, hypertrichosis and abnormal coagulation.

167
(60.4%)

thrombocythemia 1

Acrocyanosis Hypertension Splenomegaly Thrombocytosis

Autosomal dominant inheritance

168
(59.9%)

paroxysmal nocturnal hemoglobinuria 2

Hemolytic anemia Paroxysmal nocturnal hemoglobinuria Urticaria

Autosomal dominant inheritance Somatic mutation

Any paroxysmal nocturnal hemoglobinuria in which the cause of the disease is a mutation in the PIGT gene.

168
(59.9%)

Fabry disease

Anemia Angiokeratoma Proteinuria

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.

168
(59.9%)

Wiskott-Aldrich syndrome

Decreased specific anti-polysaccharide antibody level Hemolytic anemia Petechiae

X-linked recessive inheritance

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disease characterized by microthrombocytopenia, eczema, infections and an increased risk for autoimmune manifestations and malignancies.

168
(59.9%)

Fanconi anemia complementation group C

Anemia Bruising susceptibility Deficient excision of UV-induced pyrimidine dimers in DNA Reticulocytopenia

Autosomal recessive inheritance

Fanconi anemia caused by mutations of the FANCC gene. This gene provides instructions for making a protein that delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA.

168
(59.9%)

Fanconi anemia complementation group E

Anemia Bruising susceptibility Deficient excision of UV-induced pyrimidine dimers in DNA Reticulocytopenia

Autosomal recessive inheritance

Fanconi anemia caused by mutations of the FANCE gene. This is a protein coding gene. It is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2.

168
(59.9%)

Fanconi anemia complementation group A

Anemia Bruising susceptibility Deficient excision of UV-induced pyrimidine dimers in DNA Reticulocytopenia

Autosomal recessive inheritance

Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway.

168
(59.9%)

Fanconi anemia complementation group D2

Anemia Bruising susceptibility Deficient excision of UV-induced pyrimidine dimers in DNA Reticulocytopenia

Autosomal recessive inheritance

Fanconi anemia caused by mutations of the FANCD2 gene. This gene is involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing.

175
(59.8%)

congenital disorder of glycosylation type 1E

Reduced antithrombin III activity Splenomegaly Telangiectasia Type I transferrin isoform profile

Autosomal recessive inheritance

The CDG (Congenital Disorders of Glycosylation) syndromes are a group of autosomal recessive disorders affecting glycoprotein synthesis. CDG syndrome type Ie is characterised by psychomotor delay, seizures, hypotonia, facial dysmorphism and microcephaly. Ocular anomalies are also very common.

176
(59.7%)

juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome

Anemia Epistaxis Hepatic arteriovenous malformation Telangiectasia

Autosomal dominant inheritance

176
(59.7%)

dyskeratosis congenita, autosomal dominant 1

Anemia Carious teeth Cirrhosis Premature graying of hair

Autosomal dominant inheritance

A dyskeratosis congenita that has material basis in an autosomal dominant mutation of TERC on chromosome 3q26.2.

176
(59.7%)

dyskeratosis congenita, X-linked

Anemia Cirrhosis Cryptorchidism Premature graying of hair

X-linked recessive inheritance

X-linked form of dyskeratosis congenita.

179
(59.6%)

hyper-IgM syndrome type 4

Absence of lymph node germinal center Autoimmune hemolytic anemia Impaired Ig class switch recombination Recurrent infection of the gastrointestinal tract

Autosomal recessive inheritance

A form of Hyper IgM syndrome which is a defect in class switch recombination downstream of the AICDA gene that does not impair somatic hypermutation.

179
(59.6%)

combined immunodeficiency due to LRBA deficiency

Autoimmune hemolytic anemia Chronic diarrhea Decreased circulating IgA level Lymphadenopathy

Autosomal recessive inheritance