589
(44.8%)

low phospholipid associated cholelithiasis

Elevated alkaline phosphatase Jaundice

Autosomal dominant inheritance Autosomal recessive inheritance

Low phospholipid associated cholelithiasis is a rare genetic hepatic disease characterized by cholesterol gallstones and intrahepatic stones developing before the age of 40 years.

589
(44.8%)

Edinburgh malformation syndrome

Hydrocephalus Jaundice Neonatal hyperbilirubinemia

Autosomal dominant inheritance

Edinburgh malformation syndrome is a rare, genetic, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by consistently abnormal facial appearance, true or apparent hydrocephalus, motor and cognitive developmental delay, failure to thrive (feeding difficulties, vomiting, chest infections) and death within a few months of birth. Carp mouth, hairiness of the forehead, neonatal hyperbilirubinemia and advanced bone age may also be associated. There have been no further descriptions in the literature since 1991.

589
(44.8%)

arteritis, familial granulomatous, with juvenile polyarthritis

Fever Hypertension Jaundice

Autosomal dominant inheritance

589
(44.8%)

biliary malformation with renal tubular insufficiency

Jaundice Proteinuria

Autosomal dominant inheritance X-linked recessive inheritance

589
(44.8%)

arthrogryposis, renal dysfunction, and cholestasis 2

Jaundice Metabolic acidosis Nephropathy

Autosomal recessive inheritance

Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VIPAS39 gene.

589
(44.8%)

microcephaly, epilepsy, and diabetes syndrome 1

Cryptorchidism Diabetes mellitus Jaundice

Autosomal recessive inheritance

589
(44.8%)

asphyxiating thoracic dystrophy 1

Jaundice Proteinuria Renal insufficiency

Autosomal recessive inheritance

An asphyxiating thoracic dystrophy associated with variation in the region 15q13.

589
(44.8%)

Alagille syndrome due to a JAG1 point mutation

Cirrhosis Prolonged neonatal jaundice Renal tubular acidosis Vesicoureteral reflux

Autosomal dominant inheritance

609
(44.8%)

Perlman syndrome

Cryptorchidism Edema Pancreatic islet-cell hyperplasia Visceromegaly

Autosomal recessive inheritance

Perlman syndrome is characterized principally by polyhydramnios, neonatal macrosomia, bilateral renal tumours (hamartomas with or without nephroblastomatosis), hypertrophy of the islets of Langerhans and facial dysmorphism.

610
(44.8%)

telangiectasia, hereditary hemorrhagic, type 5

Portal hypertension Spontaneous, recurrent epistaxis Telangiectasia

Autosomal dominant inheritance

Any hereditary hemorrhagic telangiectasia in which the cause of the disease is a mutation in the GDF2 gene.

610
(44.8%)

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2

Cirrhosis Leukemia Premature graying of hair

Autosomal dominant inheritance

610
(44.8%)

cerebroretinal microangiopathy with calcifications and cysts 2

Osteopenia Pancytopenia Portal hypertension Premature graying of hair

Autosomal recessive inheritance

Any Coats plus syndrome in which the cause of the disease is a mutation in the STN1 gene.

610
(44.8%)

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1

Cirrhosis Leukemia Premature graying of hair

Autosomal dominant inheritance

Any pulmonary fibrosis and/or bone marrow failure, Telomere-related in which the cause of the disease is a mutation in the TERT gene.

610
(44.8%)

spondyloepimetaphyseal dysplasia, Krakow type

Annular pancreas Bruising susceptibility High palate

Autosomal recessive inheritance

615
(44.7%)

Woronets trait

Red blood cell keratocytosis

Autosomal dominant inheritance

615
(44.7%)

red cell permeability defect

Elliptocytosis

Autosomal dominant inheritance

615
(44.7%)

Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome

Elliptocytosis Intellectual disability

Contiguous gene syndrome

615
(44.7%)

elliptocytosis 2

Elliptocytosis

Autosomal dominant inheritance Heterogeneous

Any hereditary elliptocytosis in which the cause of the disease is a mutation in the SPTA1 gene.

619
(44.7%)

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

Elevated erythrocyte sedimentation rate Inflammation of the large intestine Lymphadenopathy Thrombocytopenia

Autosomal recessive inheritance

619
(44.7%)

infantile-onset periodic fever-panniculitis-dermatosis syndrome

Diarrhea Joint swelling Leukocytosis Lymphadenopathy

Autosomal recessive inheritance

621
(44.6%)

STT3B-CDG

Abnormal glycosylation Decreased liver function Thrombocytopenia

Autosomal recessive inheritance

STT3B-CDG is a form of congenital disorders of N-linked glycosylation characterized by intrauterine growth retardation, microcephaly, failure to thrive, developmental delay, intellectual disability, hypotonia, seizures, optic nerve atrophy and respiratory difficulties. Genital abnormalities (micropenis, hypoplastic scrotum, undescended testes) have also been reported. STT3B-CDG is caused by mutations in the gene STT3B (3p24.1).

621
(44.6%)

SSR4-CDG

Abnormality of coagulation Feeding difficulties Type I transferrin isoform profile

X-linked recessive inheritance

(Xq28).

623
(44.4%)

HELLP syndrome

Elevated hepatic transaminase Proteinuria Thrombocytopenia

Autosomal dominant inheritance

HELLP syndrome is a life-threatening condition that can potentially complicate pregnancy. It is named for 3 features of the condition: H emolysis, E levated L iver enzyme levels, and L ow P latelet levels. It typically occurs in the last 3 months of pregnancy (the third trimester) but can also start soon after delivery. A wide range of non-specific symptoms may be present in women with HELLP syndrome. Symptoms may include fatigue; malaise; fluid retention and excess weight gain; headache; nausea and vomiting; pain in the upper right or middle of the abdomen; blurry vision; and rarely, nosebleed or seizures. The cause of HELLP syndrome is not known, but certain risk factors have been associated with the condition. It is most common in women with preeclampsia or eclampsia. If not diagnosed and treated quickly, HELLP syndrome can lead to serious complications for the mother and baby.The main treatment is to deliver the baby as soon as possible, even if premature. Treatment may also includemedications needed for the mother or baby, and blood transfusion for severe bleeding problems.

623
(44.4%)

chondroitin-6-sulfaturia, defective cellular immunity, nephrotic syndrome

Abnormal T cell morphology Macronodular cirrhosis Proteinuria

Autosomal recessive inheritance

623
(44.4%)

acyl-CoA dehydrogenase 9 deficiency

Hypoglycemia Microvesicular hepatic steatosis Thrombocytopenia

Autosomal recessive inheritance

Acyl-CoA dehydrogenase 9 (ACAD9) deficiency is a rare disorder leading to a deficiency of complex I of the respiratory chain and is characterized by neurological dysfunction, hepatic failure and cardiomyopathy.

623
(44.4%)

immunoskeletal dysplasia with neurodevelopmental abnormalities

Decreased circulating antibody level Eosinophilia Hepatic cysts

Autosomal recessive inheritance

623
(44.4%)

mitochondrial DNA depletion syndrome 13

Elevated hepatic transaminase Neutropenia Renal tubular acidosis

Autosomal recessive inheritance

Any mitochondrial DNA depletion syndrome in which the cause of the disease is a mutation in the FBXL4 gene.

628
(44.3%)

congenital disorder of glycosylation, type IIq

Abnormal glycosylation Elevated hepatic transaminase Seizure

Autosomal recessive inheritance

628
(44.3%)

TMEM199-CDG

Abnormal protein N-linked glycosylation Global developmental delay Hepatic steatosis

Autosomal recessive inheritance

628
(44.3%)

DPM3-CDG

Elevated hepatic transaminase Muscle weakness Type I transferrin isoform profile

Autosomal recessive inheritance

DPM3-CDG is an extremely rare form of CDG syndrome characterized clinically in the single reported case by muscle weakness, waddling gait and dilated cardiomyopathy.

628
(44.3%)

congenital muscular dystrophy with intellectual disability and severe epilepsy

Abnormal isoelectric focusing of serum transferrin Elevated hepatic transaminase High palate

Autosomal recessive inheritance

632
(44.2%)

pancytopenia and occlusive vascular disease

Anemia Peripheral arterial stenosis Thrombocytopenia

Autosomal dominant inheritance

632
(44.2%)

Diamond-Blackfan anemia 6

Cleft palate Macrocytic anemia Tetralogy of Fallot

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL5 gene.

632
(44.2%)

Diamond-Blackfan anemia 10

Anemia Ectopic kidney Patent ductus arteriosus Reticulocytopenia

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS26 gene.

632
(44.2%)

alpha thalassemia-intellectual disability syndrome type 1

Cryptorchidism Hypochromic microcytic anemia Patent ductus arteriosus

Autosomal dominant inheritance Contiguous gene syndrome

Alpha-thalassemia-intellectual deficit syndrome linked to chromosome 16 (ATR-16), a contiguous gene deletion syndrome, is a form of alpha-thalassemia characterized by microcytosis, hypochromia, normal hemoglobin (Hb) level or mild anemia, associated with developmental abnormalities.

636
(44.1%)

autoimmune hemolytic anemia

Abnormality of metabolism/homeostasis Autoimmune hemolytic anemia

Autosomal recessive inheritance

Autoimmune hemolytic anemia (AIHA) is an autoimmune disorder in which various types of auto-antibodies are directed against red blood cells causing their survival to be shortened and resulting in hemolytic anemia.

636
(44.1%)

Dohle bodies and leukemia

Acute myeloid leukemia Anemia Lymphedema

Autosomal recessive inheritance

636
(44.1%)

lymphopenic hypergammaglobulinemia, antibody deficiency, autoimmune hemolytic anemia, and glomerulonephritis

Autoimmune hemolytic anemia Glomerulonephritis Increased circulating antibody level

Autosomal recessive inheritance

636
(44.1%)

formiminoglutamic aciduria

Aminoaciduria Hypersegmentation of neutrophil nuclei Intellectual disability Megaloblastic anemia

Autosomal recessive inheritance

Formiminoglutamic aciduria, in its moderate form and in the absence of histidine administration, is characterized by mild developmental delay and elevated concentrations of formiminoglutamate (FIGLU) in the urine. A more severe phenotype has been described in five members of a Japanese family and included severe intellectual deficit, psychomotor retardation and megaloblastic anemia.

636
(44.1%)

Fanconi anemia complementation group V

Anemia Elevated alpha-fetoprotein Microcephaly Neutropenia

Autosomal recessive inheritance

Any Fanconi anemia in which the cause of the disease is a mutation in the MAD2L2 gene.

636
(44.1%)

immunoglobulin-mediated membranoproliferative glomerulonephritis

Glomerulonephritis Hemolytic anemia Proteinuria

Autosomal recessive inheritance

Glomerulonephritis characterized by mesangial proliferation, endocapillary proliferation, and glomerular capillary wall remodeling with immune complex deposits from classical complement pathway activation.

636
(44.1%)

bone marrow failure syndrome 5

Anemia Decreased circulating antibody level Testicular atrophy

Autosomal dominant inheritance

636
(44.1%)

neutropenia, severe congenital, 1, autosomal dominant

Anemia Growth abnormality Increased circulating antibody level Neutropenia

Autosomal dominant inheritance

636
(44.1%)

glutathione synthetase deficiency with 5-oxoprolinuria

Chronic metabolic acidosis Hemolytic anemia Neutropenia Pigmentary retinopathy

Autosomal recessive inheritance

636
(44.1%)

Wolfram syndrome, mitochondrial form

Diabetes mellitus Hydroureter Megaloblastic anemia Neutropenia

Autosomal recessive inheritance Mitochondrial inheritance

636
(44.1%)

autosomal recessive Kenny-Caffey syndrome

Anemia Hypertelorism Hypocalcemia Recurrent bacterial infections

Autosomal recessive inheritance

An autosomal recessive form of Kenny-Caffey syndrome due to mutation(s) in the TBCE gene, encoding tubulin-specific chaperone E. This condition is characterized by hypoparathyroidism with hypocalcemia, marked growth retardation, craniofacial anomalies, absent diploic space in the skull, cortical thickening of long bones with medullary stenosis, and small hands and feet.

647
(44.1%)

isobutyryl-CoA dehydrogenase deficiency

Anemia Decreased plasma carnitine Dilated cardiomyopathy Hypotonia

Autosomal recessive inheritance

Isobutyryl-CoA dehydrogenase deficiency is an inborn error of valine metabolism. The prevalence is unknown. Only one symptomatic patient (with anaemia, failure to thrive, dilated cardiomyopathy and plasma carnitine deficiency) has been described so far, but several series of patients have been identified through newborn screening programs relying on detection of increased C(4)-carnitine levels by tandem mass spectrometry. The disorder is caused by mutations in the ACAD8 gene (11q25).

647
(44.1%)

non-immune hydrops fetalis

Anemia Congestive heart failure Nonimmune hydrops fetalis

Non-immune hydrops fetalis (NIHF), a form of HF, is a severe fetal condition defined as the excessive accumulation of fetal fluid within the fetal extravascular compartments and body cavities, and is the end-stage of a wide variety of disorders.

647
(44.1%)

Diamond-Blackfan anemia 12

Elevated red cell adenosine deaminase level Normochromic anemia Triphalangeal thumb Ventricular septal defect

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL15 gene.

647
(44.1%)

focal segmental glomerulosclerosis 1

Anemia Hypertension Proteinuria

Autosomal dominant inheritance

Any focal segmental glomerulosclerosis in which the cause of the disease is a mutation in the ACTN4 gene.

647
(44.1%)

atypical hemolytic-uremic syndrome with I factor anomaly

Hypertension Microangiopathic hemolytic anemia Proteinuria

Autosomal dominant inheritance

647
(44.1%)

atypical hemolytic-uremic syndrome with B factor anomaly

Hypertension Microangiopathic hemolytic anemia Proteinuria

Autosomal dominant inheritance

647
(44.1%)

atypical hemolytic-uremic syndrome with C3 anomaly

Hypertension Microangiopathic hemolytic anemia Proteinuria

Autosomal dominant inheritance

647
(44.1%)

atypical hemolytic-uremic syndrome with thrombomodulin anomaly

Hypertension Microangiopathic hemolytic anemia Proteinuria

Autosomal dominant inheritance

647
(44.1%)

nephronophthisis 1

Anemia Hypertension Hyposthenuria Nephronophthisis

Autosomal recessive inheritance

Progressive tubulointerstitial nephritis inherited in an autosomal recessive manner. It is caused by mutations in the NPHP1 gene. Patients present with anemia, polyuria, and polydipsia during childhood. The progressive bilateral kidney damage results in renal failure.

647
(44.1%)

atypical hemolytic-uremic syndrome with MCP/CD46 anomaly

Hypertension Microangiopathic hemolytic anemia Proteinuria

Autosomal dominant inheritance Autosomal recessive inheritance

647
(44.1%)

medullary cystic kidney disease 1

Anemia Hypertension Renal hypoplasia Renal salt wasting

Autosomal dominant inheritance

An inherited disorder that causes a gradual loss of kidney function, caused by a mutation in the MUC1 gene that leads to production of an abnormal mucin 1 protein, which deposits in the kidney and leads to slow loss of kidney function.

647
(44.1%)

hereditary myopathy with lactic acidosis due to ISCU deficiency

Increased serum lactate Muscle weakness Palpitations Sideroblastic anemia

Autosomal recessive inheritance

Aconitase deficiency is characterised by myopathy with severe exercise intolerance and deficiencies of skeletal muscle succinate dehydrogenase and aconitase.

647
(44.1%)

Kearns-Sayre syndrome

Cardiomyopathy Diabetes mellitus Microcephaly Sideroblastic anemia

Mitochondrial inheritance

Kearns-Sayre syndrome (KSS) is a mitochondrial disease characterized by progressive external ophthalmoplegia (PEO), pigmentary retinitis and an onset before the age of 20 years. Common additional features include deafness, cerebellar ataxia and heart block.

660
(44.0%)

glycogen storage disease due to GLUT2 deficiency

Impairment of galactose metabolism Malabsorption Reduced subcutaneous adipose tissue Renal tubular dysfunction

Autosomal recessive inheritance

Fanconi-Bickel glycogenosis (FBG) is a rare glycogen storage disease characterized by hepatorenal glycogen accumulation, severe renal tubular dysfunction and impaired glucose and galactose metabolism.

660
(44.0%)

wrinkly skin syndrome

Abnormal isoelectric focusing of serum transferrin Inguinal hernia Neonatal wrinkled skin of hands and feet

Autosomal recessive inheritance

Wrinkly skin syndrome (WSS) is characterized by wrinkling of the skin of the dorsum of the hands and feet, an increased number of palmar and plantar creases, wrinkled abdominal skin, multiple skeletal abnormalities (joint laxity and congenital hip dislocation), late closing of the anterior fontanel, microcephaly, pre- and postnatal growth retardation, developmental delay and facial dysmorphism (a broad nasal bridge, downslanting palpebral fissures and hypertelorism).

662
(43.9%)

deafness, autosomal dominant 34, with or without inflammation

Conjunctivitis Lymphadenopathy Periodic fever Urticaria

Autosomal dominant inheritance

662
(43.9%)

lymphedema, hereditary, 1A

Hydrocele testis Hypoplasia of lymphatic vessels Nonimmune hydrops fetalis Prominent superficial veins

Autosomal dominant inheritance

Any hereditary lymphedema in which the cause of the disease is a mutation in the FLT4 gene.

662
(43.9%)

hypotrichosis-lymphedema-telangiectasia-renal defect syndrome

Hydrocele testis Lymphedema Pulmonary lymphangiectasia Reduced subcutaneous adipose tissue

Autosomal dominant inheritance

665
(43.7%)

osteocraniostenosis

Asplenia Hypocalcemia Micropenis

Autosomal dominant inheritance

Osteocraniostenosis is a lethal skeletal dysplasia characterized by a cloverleaf skull anomaly, facial dysmorphism, limb shortness, splenic hypo/aplasia and radiological anomalies including thin tubular bones with flared metaphyses and deficient calvarial mineralization.

666
(43.7%)

polycystic liver disease 2

Hepatic cysts Hepatomegaly

Autosomal dominant inheritance

Any polycystic kidney disease in which the cause of the disease is a mutation in the SEC63 gene.

666
(43.7%)

3-hydroxy-3-methylglutaryl-CoA synthase deficiency

Hepatomegaly Vomiting

Autosomal recessive inheritance

3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMG-CoA synthase deficiency) is a rare autosomal recessively inherited disorder of ketone body metabolism, reported in less than 20 patients to date, characterized clinically by episodes of decompensation (often associated with gastroenteritis or fasting) that present with vomiting, lethargy, hepatomegaly, non ketotic hypoglycemia and, in rare cases, coma. Patients are mostly asymptomatic between acute epidodes. HMG-CoA synthase deficiency requires an early diagnosis in order to avoid hypoglycemic crises that can lead to permanent brain damage or death.

666
(43.7%)

ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome

Ataxia Hepatosplenomegaly

Autosomal recessive inheritance

Ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome is characterised by ichthyosis, hepatosplenomegaly and late-onset cerebellar ataxia. It has been described in two brothers. Transmission is either autosomal recessive or X-linked.

666
(43.7%)

glycogen storage disease IXb

Generalized hypotonia Hepatomegaly

Autosomal recessive inheritance

Glycogen storage disease (GSD) due to liver and muscle phosphorylase kinase (PhK) deficiency is a benign inborn error of glycogen metabolism. It is the mildest form of GSD due to PhK deficiency.

666
(43.7%)

peroxisome biogenesis disorder 3A (Zellweger)

Hepatomegaly Polycystic kidney dysplasia

Autosomal recessive inheritance

666
(43.7%)

peroxisome biogenesis disorder 4A (Zellweger)

Hepatomegaly Renal cyst

Autosomal recessive inheritance

666
(43.7%)

peroxisome biogenesis disorder 6A (Zellweger)

Hepatomegaly Renal cyst

Autosomal recessive inheritance

666
(43.7%)

FGFR2-related bent bone dysplasia

Gingival overgrowth Hepatosplenomegaly

Autosomal dominant inheritance

666
(43.7%)

porencephaly-microcephaly-bilateral congenital cataract syndrome

Cryptorchidism Hepatomegaly

Autosomal recessive inheritance

666
(43.7%)

peroxisome biogenesis disorder 10A (Zellweger)

Hepatomegaly High palate

Autosomal recessive inheritance

666
(43.7%)

Geleophysic dysplasia 2

Hepatomegaly Thin upper lip vermilion

Autosomal dominant inheritance

Any geleophysic dysplasia in which the cause of the disease is a mutation in the FBN1 gene.

666
(43.7%)

geleophysic dysplasia 3

Hepatomegaly Round face

Autosomal dominant inheritance

666
(43.7%)

acrocephalopolydactyly

Enlarged kidney Hepatic fibrosis Hepatomegaly

Autosomal recessive inheritance

Acrocephalopolydactyly, also known as Elejalde syndrome, is an extremely rare lethal autosomal recessive disorder characterized by massive birth weight, swollen globular body, generalized edema, short limbs, postaxial polydactyly, thick skin, facial dysmorphism (slanted palpebral fissures, hypertelorism, epicanthic folds, dysplastic ears), excessive connective tissue, renal dysplasia, and in some patients, organomegaly, craniosynostosis with acrocephaly, omphalocele, cleft palate, and cryptorchidism. Fewer than 10 cases have been reported to date.

666
(43.7%)

mulibrey nanism

Hepatomegaly Microglossia

Autosomal recessive inheritance

MULIBREY nanism (MUL) is a prenatal onset growth disorder with multiorgan manifestations.

666
(43.7%)

peroxisomal acyl-CoA oxidase deficiency

Brachycephaly Hepatomegaly

Autosomal recessive inheritance

Peroxisomal acyl-CoA oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy.

666
(43.7%)

Joubert syndrome with oculorenal defect

Hepatic fibrosis Hepatomegaly Nephronophthisis

Autosomal recessive inheritance

Joubert syndrome with oculorenal defect is a rare subtype of Joubert syndrome and related disorders (JSRD) characterized by the neurological features of JS associated with both renal and ocular disease.

666
(43.7%)

infantile multisystem neurologic-endocrine-pancreatic disease

Hepatic fibrosis Hepatomegaly Shawl scrotum

Autosomal recessive inheritance

666
(43.7%)

geleophysic dysplasia 1

Hepatomegaly Wide mouth

Autosomal recessive inheritance

Any geleophysic dysplasia in which the cause of the disease is a mutation in the ADAMTSL2 gene.

666
(43.7%)

C syndrome

Cryptorchidism Hepatomegaly

Autosomal dominant inheritance

C syndrome is a rare multiple congenital anomaly/intellectual disability syndrome characterized by trigonocephaly and metopic suture synostosis, dysmorphic facial features, short neck, skeletal anomalies, and variable intellectual disability.

685
(43.5%)

cephalin lipidosis

Abnormality of metabolism/homeostasis Abnormality of the spleen Intellectual disability

Autosomal recessive inheritance

686
(43.3%)

hyperbiliverdinemia

Cholelithiasis Cholestasis Green urine

Autosomal dominant inheritance Autosomal recessive inheritance

Hyperbiliverdinemia is a rare, genetic hepatic disease characterized by the presence of green coloration of the skin, urine, plasma and other body fluids (ascites, breastmilk) or parts (sclerae) due to increased serum levels of biliverdin in association with biliary obstruction and/or liver failure. Association with malnutrition, medication, and congenital biliary atresia has also been reported.

686
(43.3%)

gracile syndrome

Cholestasis Increased circulating ferritin concentration Neonatal hypotonia

Autosomal recessive inheritance

GRACILE syndrome is an inherited lethal mitochondrial disorder characterized by fetal growth restriction (GR), aminoaciduria (A), cholestasis (C), iron overload (I), lactacidosis (L), and early death (E).

686
(43.3%)

neonatal intrahepatic cholestasis due to citrin deficiency

Cirrhosis Hypertriglyceridemia Intrahepatic cholestasis

Autosomal recessive inheritance

Neonatal intrahepatic cholestasis due to citrin deficiency is a mild subtype of citrin deficiency characterized clinically by low birth weight, failure to thrive, transient intrahepatic cholestasis, multiple aminoacidemia, galactosemia, hypoproteinemia, hepatomegaly, decreased coagulation factors, hemolytic anemia, variable but mostly mild liver dysfunction, and hypoglycemia.

686
(43.3%)

obesity due to pro-opiomelanocortin deficiency

Cholestasis Decreased response to growth hormone stimuation test Hypoglycemic seizures

Autosomal recessive inheritance

Pro-opiomelanocortin (POMC) deficiency is a form of monogenic obesity resulting in severe early-onset obesity, adrenal insufficiency, red hair and pale skin.

686
(43.3%)

Mitchell-Riley syndrome

Acholic stools Annular pancreas Hyperbilirubinemia Intrauterine growth retardation

Autosomal recessive inheritance

686
(43.3%)

Alagille syndrome due to a NOTCH2 point mutation

Cholestatic liver disease Proteinuria Renal insufficiency

Autosomal dominant inheritance

686
(43.3%)

adenosine kinase deficiency

Cholestasis Hyperbilirubinemia Macrocephaly

Autosomal recessive inheritance

A rare inborn error of metabolism characterized by persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine which manifests with encephalopathy, severe global developmental delay, mild to severe liver dysfunction, hypotonia and facial dysmorphism (most significant is frontal bossing, macrocephaly, hypertelorism and depressed nasal bridge). Epileptic seizures, hypoglycemia and/or cardiac defects (pulmonary stenosis, atrial and/or ventricular septal defect, coarctation of the aorta) may be associated. Clinical picture may range from neurological symptoms only to multi-organ involvement.

686
(43.3%)

Donohue syndrome

Cholestasis Hepatic fibrosis Hyperinsulinemia Long penis

Autosomal recessive inheritance

Leprechaunism is a congenital form of extreme insulin resistance (a group of syndromes that also includes Rabson-Mensenhall syndrome, type A insulin-resistance syndrome, and acquired type B insulin-resistance syndrome) characterized by intrauterine and mainly postnatal severe growth retardation.

686
(43.3%)

Smith-Lemli-Opitz syndrome

Cholestatic liver disease Cryptorchidism Hypocholesterolemia

Autosomal recessive inheritance

Smith-Lemli-Opitz syndrome (SLOS) is characterized by multiple congenital anomalies, intellectual deficit, and behavioral problems.

695
(43.3%)

Immunoerythromyeloid hypoplasia

Decreased circulating IgG level Erythroid hypoplasia

Autosomal recessive inheritance

696
(43.1%)

hereditary chronic pancreatitis

Abnormal thrombosis Diabetes mellitus Pancreatitis

Autosomal dominant inheritance

Hereditary chronic pancreatitis (HCP), a rare inherited form of pancreatitis is defined as recurrent acute pancreatitis and/or chronic pancreatitis in two first-degree relatives or 3 or more second-degree relatives in 2 or more generations, for which no predisposing factors are identified. HCP is characterized by irreversible damage to both exocrine and endocrine components of the pancreas.

697
(42.9%)

thrombocytopenia 2

Bruising susceptibility

Autosomal dominant inheritance

An autosomal dominant disorder caused by mutation(s) in the ANKRD26 gene, encoding ANKRD26 protein. Additionally, in one family, a mutation(s) has been identified in the MASTL gene, encoding serine/threonine-protein kinase greatwall. The condition is characterized by mild to moderate bruisability.

697
(42.9%)

fibrinolytic defect

Hyperextensible skin Spontaneous hematomas

Autosomal dominant inheritance

697
(42.9%)

complement component 2 deficiency

Purpura

Autosomal recessive inheritance

Complement component 2 deficiency (C2D) is a genetic condition that affects the immune system. Signs and symptoms include recurrent bacterial infections and risk for a variety of autoimmune conditions. Infections can be very serious and are common in early life. They become less frequent during the teen and adult years. The most frequent autoimmune conditions associated with C2D are lupus (10-20%) and vasculitis. C2D is caused by mutations in the C2 gene and is inherited in an autosomal recessive fashion.

697
(42.9%)

epidermolysis bullosa simplex Ogna type

Bruising susceptibility

Autosomal dominant inheritance

Epidermolysis bullosa simplex, Ogna type (EBS-O) is a basal subtype of epidermolysis bullosa simplex (EBS) characterized by sometimes widespread, primarily acral blistering.