355
(52.5%)

Lesch-Nyhan syndrome

Hyperuricemia Megaloblastic anemia Vomiting

X-linked recessive inheritance

Lesch-Nyhan syndrome (LNS) is the most severe form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, a hereditary disorder of purine metabolism, and is associated with uric acid overproduction (UAO), neurological troubles, and behavioral problems.

355
(52.5%)

combined oxidative phosphorylation defect type 14

Anemia Feeding difficulties Increased serum lactate

Autosomal recessive inheritance

Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the FARS2 gene.

355
(52.5%)

coenzyme Q10 deficiency, primary, 1

Anemia Hepatic failure Lactic acidosis

Autosomal recessive inheritance

Any coenzyme Q10 deficiency in which the cause of the disease is a mutation in the COQ2 gene.

355
(52.5%)

alpha thalassemia-X-linked intellectual disability syndrome

Abnormality of metabolism/homeostasis Hypochromic microcytic anemia Umbilical hernia

X-linked dominant inheritance

X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal.

365
(52.5%)

Felty syndrome

Neutropenia Rheumatoid arthritis Splenomegaly

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.

366
(52.3%)

Cornelia de Lange syndrome 1

Cutis marmorata Duplication of internal organs Proteinuria Thrombocytopenia

Autosomal dominant inheritance Sporadic

Any Cornelia de Lange syndrome in which the cause of the disease is a mutation in the NIPBL gene.

367
(52.2%)

nephrotic syndrome - deafness - pretibial epidermolysis bullosa syndrome

Nephritis Nephropathy Pretibial blistering Reduced beta/alpha synthesis ratio

Autosomal recessive inheritance

368
(52.2%)

GM1 gangliosidosis type 2

Abnormality of the liver Abnormality of the spleen Decreased beta-galactosidase activity Sea-blue histiocytosis

Autosomal recessive inheritance

GM1 gangliosidosis type 2 is a clinically variable, infancy or childhood-onset form of GM1 gangliosidosis characterized by normal early development and psychomotor regression between seven months and three years of age.

369
(52.0%)

developmental and epileptic encephalopathy, 50

Abnormal glycosylation Acanthocytosis Anemia Global developmental delay

Autosomal recessive inheritance

370
(51.9%)

Halothane hepatitis

Eosinophilia Fever Jaundice

Autosomal recessive inheritance Multifactorial inheritance

370
(51.9%)

cholestasis, progressive familial intrahepatic, 5

Edema Jaundice Prolonged prothrombin time

Autosomal recessive inheritance

Any progressive familial intrahepatic cholestasis in which the cause of the disease is a mutation in the NR1H4 gene.

370
(51.9%)

infantile liver failure syndrome 2

Abnormality of the coagulation cascade Hypoglycemia Jaundice

Autosomal recessive inheritance

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

370
(51.9%)

visceral steatosis, congenital

Abnormal bleeding Hypoglycemia Jaundice

Autosomal recessive inheritance

370
(51.9%)

neonatal hemochromatosis

Abnormal bleeding Cirrhosis Nonimmune hydrops fetalis Prolonged neonatal jaundice

Autosomal recessive inheritance

Neonatal hemochromatosis is a disease in which too much iron builds up inthe body. In this form of hemochromatosis the iron overload begins before birth. This disease tends to progress rapidly and is characterized by liver damage that is apparent at birth or in the first day of life. There are a number of other forms of hemochromatosis. To learn more about these other forms click on the disease names listed below: Hemochromatosis type 1 Hemochromatosis type 2 Hemochromatosis type 3 Hemochromatosis type 4

370
(51.9%)

arthrogryposis, renal dysfunction, and cholestasis 1

Abnormal bleeding Jaundice Metabolic acidosis

Autosomal recessive inheritance

Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VPS33B gene.

376
(51.8%)

developmental and epileptic encephalopathy, 36

Hepatomegaly Hydrocephalus Type I transferrin isoform profile

X-linked inheritance X-linked recessive inheritance X-linked dominant inheritance

377
(51.7%)

renal-hepatic-pancreatic dysplasia 2

Cholestasis Enlarged kidney Hepatomegaly

Autosomal recessive inheritance

Any renal-hepatic-pancreatic dysplasia in which the cause of the disease is a mutation in the NEK8 gene.

377
(51.7%)

NPHP3-related Meckel-like syndrome

Cholestasis Hepatosplenomegaly Multicystic kidney dysplasia

Autosomal recessive inheritance

377
(51.7%)

renal-hepatic-pancreatic dysplasia 1

Cholestasis Hepatomegaly Renal insufficiency

Autosomal recessive inheritance

Any renal-hepatic-pancreatic dysplasia in which the cause of the disease is a mutation in the NPHP3 gene.

377
(51.7%)

d-bifunctional protein deficiency

Cholestasis Hepatomegaly Renal cyst

Autosomal recessive inheritance

D-bifunctional protein deficiency (DBP deficiency)is a genetic disorder that affects the ability of the body to effectively break down fat from our diet. It is typically characterized by hypotonia (low muscle tone) and seizures in the newborn period. Other symptoms include unusual facial features and an enlarged liver (hepatomegaly). Most babies with this condition nevergain anydevelopmental skills and do not survive past the age of 2. DBP deficiency is caused by mutations in the HSD17B4 gene and is inherited in an autosomal recessive manner. Some researchers have suggested classifying DBP deficiency into three subtypes, depending on how severely the mutation in the HSD17B4 gene affects the function of the gene and the protein that it codes for. Almost all individuals with types I, II, and III have similar signs and symptoms. A fourth subtype has additionally been proposed for individuals that have less severe symptoms. While there is no cure for DBP deficiency, treatment is focused on improving nutrition and growth, controlling symptoms, and limiting the progression of liver disease.

381
(51.7%)

DDX41-related hematologic malignancy predisposition syndrome

Eczema Refractory anemia

Autosomal dominant inheritance

Any hereditary neoplastic syndrome in which the cause of the disease is a mutation in the DDX41 gene.

382
(51.4%)

developmental and epileptic encephalopathy, 66

Anemia Cryptorchidism Neutropenia Synophrys

Autosomal dominant inheritance

383
(51.4%)

X-linked dyserythropoetic anemia with abnormal platelets and neutropenia

Elliptocytosis Macrocytic anemia Neutropenia Thrombocytopenia

X-linked recessive inheritance

384
(51.2%)

ataxia-telangiectasia with generalized skin pigmentation and early death

Abnormality of the thymus Conjunctival telangiectasia Glucose intolerance Leukemia

Autosomal recessive inheritance

384
(51.2%)

ataxia telangiectasia

Conjunctival telangiectasia Diabetes mellitus Hypoplasia of the thymus Leukemia

Autosomal recessive inheritance

Ataxia-telangiectasia is the association of severe combined immunodeficiency (affecting mainly the humoral immune response) with progressive cerebellar ataxia. It is characterised by neurological signs, telangiectasias, increased susceptibility to infections and a higher risk of cancer.

386
(51.1%)

Caroli disease

Cholangitis Hepatomegaly Portal hypertension Recurrent fever

Caroli disease (CD) is a rare congenital liver disease characterized by non-obstructive cystic dilatations of the intra-hepatic and rarely extra-hepatic bile ducts.

386
(51.1%)

mitochondrial DNA depletion syndrome 4a

Bile duct proliferation Hepatomegaly Increased serum lactate Visual loss

Autosomal recessive inheritance

Alpers Huttenlocher syndrome (AHS) is a cerebrohepatopathy and a rare and severe form of mitochondrial DNA (mtDNA) depletion syndrome characterized by the triad of progressive developmental regression, intractable seizures, and hepatic failure.

386
(51.1%)

cranioectodermal dysplasia 1

Hepatomegaly High palate Hypocalcemia Malformation of the hepatic ductal plate

Autosomal recessive inheritance

Any cranioectodermal dysplasia in which the cause of the disease is a mutation in the IFT122 gene.

389
(51.1%)

familial isolated congenital asplenia

Abnormality of metabolism/homeostasis Asplenia Thrombocytosis

Autosomal dominant inheritance

Familial isolated congenital asplenia is a rare, non-syndromic, potentially life-threatening visceral malformation characterized by the absence of normal spleen function, resulting in a primary immunodeficiency. Typically, the condition manifests with severe, recurrent, overwhelming infections (especially pneumococcal sepsis) in otherwise apparently healthy infants. In adults with no history of severe sepsis in infancy, thrombocytosis may be the presenting sign. Howell-Jolly bodies on blood smears and an absent spleen on abdominal ultrasound examination are highly suggestive associated findings.

390
(51.0%)

ALG2-CDG

Abnormality of coagulation Hepatomegaly Visual impairment

Autosomal recessive inheritance

A form of congenital disorders of N-linked glycosylation characterized by iris coloboma, cataract, infantile spasms, developmental delay and abnormal coagulation factors. The disease is caused by loss-of-function mutations in the gene ALG2 (9q31.1). Transmission is autosomal recessive.

390
(51.0%)

Dorfman-Chanarin disease

Abnormality of blood and blood-forming tissues Everted lower lip vermilion Hepatic steatosis Hepatomegaly

Autosomal recessive inheritance

390
(51.0%)

Aicardi-Goutieres syndrome 3

Hepatosplenomegaly Progressive microcephaly Thrombocytopenia

Autosomal recessive inheritance

Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the RNASEH2C gene.

393
(50.8%)

mitochondrial complex III deficiency nuclear type 1

Abnormality of the coagulation cascade Cholestasis Metabolic acidosis

Autosomal recessive inheritance Mitochondrial inheritance

Any mitochondrial complex III deficiency in which the cause of the disease is a mutation in the BCS1L gene.

394
(50.5%)

lethal congenital glycogen storage disease of heart

Ascites Cyanosis Macroglossia Neonatal hypoglycemia

Autosomal dominant inheritance

Any glycogen storage disease in which the cause of the disease is a mutation in the PRKAG2 gene.

395
(50.4%)

hereditary folate malabsorption

Diarrhea Folate-responsive megaloblastic anemia Oral ulcer

Autosomal recessive inheritance

Hereditary folate malabsorption (HFM) is an inherited disorder of folate transport characterized by a systemic and central nervous system (CNS) folate deficiency manifesting as megaloblastic anemia, failure to thrive, diarrhea and/or oral mucositis, immunologic dysfunction and neurological disorders.

395
(50.4%)

chromosome 15q25 deletion syndrome

Inguinal hernia Macrocytic anemia

Autosomal dominant inheritance

397
(50.0%)

Roberts-SC phocomelia syndrome

Accessory spleen Biliary tract abnormality Cryptorchidism Premature separation of centromeric heterochromatin

Autosomal recessive inheritance

A rare genetic syndrome with an autosomal recessive pattern of inheritance. It is caused by a mutation in the ESCO2 gene. Clinical signs at birth include multiple limb and facial abnormalities.

398
(49.9%)

familial apolipoprotein C-II deficiency

Hepatomegaly Hypertriglyceridemia Lipemia retinalis Splenomegaly

Autosomal recessive inheritance

398
(49.9%)

hyperlipoproteinemia, type 1D

Hepatomegaly Hyperlipoproteinemia Lipemia retinalis Splenomegaly

Autosomal recessive inheritance

Any familial hyperlipidemia in which the cause of the disease is a mutation in the GPIHBP1 gene.

398
(49.9%)

splenoportal vascular anomalies

Cirrhosis Diabetes mellitus Splenomegaly

Autosomal recessive inheritance

398
(49.9%)

transient infantile hypertriglyceridemia and hepatosteatosis

Hepatic fibrosis Hypertriglyceridemia Splenomegaly

Autosomal recessive inheritance

398
(49.9%)

combined immunodeficiency due to ZAP70 deficiency

Eczematoid dermatitis Hepatomegaly Panhypogammaglobulinemia Splenomegaly

Autosomal recessive inheritance

Combined immunodeficiency due to ZAP70 deficiency is a very rare, severe, genetic, combined immunodeficiency disorder characterized by lymphocytosis, decreased peripheral CD8+ T-cells, and presence of normal circulating CD4+ T-cells, leading to immune dysfunction.

398
(49.9%)

encephalopathy due to prosaposin deficiency

Abnormal glycosphingolipid metabolism Hepatomegaly Optic atrophy Splenomegaly

Autosomal recessive inheritance

Encephalopathy due to prosaposin deficiency is a lysosomal storage disease belonging to the group of sphingolipidoses.

398
(49.9%)

hemochromatosis type 2A

Azoospermia 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 HJV gene.

398
(49.9%)

polycystic kidney disease 4

Dehydration Periportal fibrosis Renal insufficiency Splenomegaly

Autosomal recessive inheritance

A autosomal dominant polycystic kidney disease that has material basis in mutation in the PKD4 gene.

398
(49.9%)

acrodermatitis enteropathica

Hepatomegaly Hypogonadism Low alkaline phosphatase Splenomegaly

Autosomal recessive inheritance

Acrodermatitis enteropathica (AE) is a rare inherited inborn error of metabolism resulting in a severe zinc deficiency and characterized by acral dermatitis, alopecia, diarrhea and growth failure.

398
(49.9%)

Tangier disease

Decreased HDL cholesterol concentration Hepatomegaly Splenomegaly Visual impairment

Autosomal recessive inheritance

Tangier disease (TD) is a rare lipoprotein metabolism disorder characterized biochemically by an almost complete absence of plasma high-density lipoproteins (HDL), and clinically by liver, spleen, lymph node and tonsil enlargement along with peripheral neuropathy in children and adolescents, and, occasionally, cardiovascular disease in adults.

398
(49.9%)

glycogen storage disease II

Fever Hepatomegaly Macroglossia Splenomegaly

Autosomal recessive inheritance

Glycogen storage disease due to acid maltase deficiency (AMD) is an autosomal recessive trait leading to metabolic myopathy that affects cardiac and respiratory muscles in addition to skeletal muscle and other tissues. AMD represents a wide spectrum of clinical presentations caused by an accumulation of glycogen in lysosomes: Glycogen storage disease due to acid maltase deficiency, infantile onset, non-classic infantile onset and adult onset. Early onset forms are more severe and often fatal.

398
(49.9%)

Sanfilippo syndrome type A

Dense calvaria Heparan sulfate excretion in urine Hepatomegaly Splenomegaly

Autosomal recessive inheritance

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme heparan sulfate sulfatase. It is characterized by behavioral changes, sleep disturbances, mental developmental delays and seizures.

398
(49.9%)

sterile multifocal osteomyelitis with periostitis and pustulosis

Hepatomegaly Hyperkeratosis Joint swelling Splenomegaly

Autosomal recessive inheritance

An autoinflammatory disease caused by mutations in the IL1RN gene, which encodes the IL1 receptor antagonist. It presents in infancy, and is characterized by systemic inflammation, pustular rash, bone pain, sterile osteitis, and periostitis.

398
(49.9%)

Sanfilippo syndrome type B

Dense calvaria Heparan sulfate excretion in urine Hepatomegaly Splenomegaly

Autosomal recessive inheritance

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme N-acetyl-alpha-D-glucosaminidase. It is characterized by behavioral changes, sleep disturbances, and mental developmental delays.

398
(49.9%)

COG4-CDG

Cirrhosis Elevated alkaline phosphatase Microcephaly Splenomegaly

Autosomal recessive inheritance

COG4-CDG is an extremely rare form of CDG syndrome characterized clinically in the single reported case to date by seizures, some dysmorphic features, axial hyponia, slight peripheral hypertonia and hyperreflexia.

398
(49.9%)

biotinidase deficiency

Hepatomegaly Hyperammonemia Sensorineural hearing impairment Splenomegaly

Autosomal recessive inheritance

Biotinidase deficiency is a late-onset form of multiple carboxylase deficiency, an inborn error of biotin metabolism that, if untreated, is characterized by seizures, breathing difficulties, hypotonia, skin rash, alopecia, hearing loss and delayed development.

398
(49.9%)

sialuria

Abnormality of metabolism/homeostasis Hepatomegaly Inguinal hernia Splenomegaly

Autosomal dominant inheritance

Sialuria is an extremely rare metabolic disorder described in fewer than 10 patients to date and characterized by variable signs and symptoms, mostly in infancy, including transient failure to thrive, slightly prolonged neonatal jaundice, equivocal or mild hepatomegaly, microcytic anemia, frequent upper respiratory infections, gastroenteritis, dehydration and flat and coarse facies. Learning difficulties and seizures may occur in childhood.

398
(49.9%)

Sanfilippo syndrome type C

Everted lower lip vermilion Heparan sulfate excretion in urine Hepatomegaly Splenomegaly

Autosomal recessive inheritance

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme acetyl-CoA:alpha-glucosaminide acetyltransferase. It is characterized by behavioral changes, sleep disturbances, and mental developmental delays.

398
(49.9%)

mucosulfatidosis

Hepatomegaly Hydrocephalus Mucopolysacchariduria Splenomegaly

Autosomal recessive inheritance

Multiple sulfatase deficiency (MSD) is a very rare and fatal lysosomal storage disease characterized by a clinical phenotype that combines the features of different sulfatase deficiencies (whether lysosomal or not) that can have neonatal (most severe), infantile (most common) and juvenile (rare) presentations with manifestations including hypotonia, coarse facial features, mild deafness, skeletal anomalies, ichthyosis, hepatomegaly, developmental delay, progressive neurologic deterioration and hydrocephalus.

398
(49.9%)

Sanfilippo syndrome type D

Heparan sulfate excretion in urine Hepatomegaly Splenomegaly Wide mouth

Autosomal recessive inheritance

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme N-acetylglucosamine-6-sulfatase. It is characterized by behavioral changes, sleep disturbances and mental developmental delays.

398
(49.9%)

congenital generalized lipodystrophy type 4

Hepatic steatosis Hyperinsulinemia Splenomegaly

Autosomal recessive inheritance

Any congenital generalized lipodystrophy in which the cause of the disease is a mutation in the CAVIN1 gene.

398
(49.9%)

mucopolysaccharidosis type 6

Dermatan sulfate excretion in urine Hepatomegaly Inguinal hernia Splenomegaly

Autosomal recessive inheritance

Mucopolysaccharidosis type 6 (MPS 6) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B (ASB) leading to the accumulation of dermatan sulfate.

398
(49.9%)

mullerian derivatives-lymphangiectasia-polydactyly syndrome

Hepatomegaly Inguinal hernia Lymphedema Splenomegaly

Autosomal recessive inheritance

Mullerian derivatives-lymphangiectasia-polydactyly syndrome is characterised by prenatal linear growth deficiency, hypertrophied alveolar ridges, redundant nuchal skin, postaxial polydactyly and cryptorchidism. Mullerian duct remnants, lymphangiectasis, and renal anomalies are also present. Three cases have been described. A small penis was observed in two of these cases. The syndrome is likely to be an autosomal recessive or X-linked trait. All the reported patients died neonatally of hepatic failure.