Hepatomegaly, and Autistic behavior

Alpha-N-acetylgalactosaminidase (NAGA) deficiency type 3 is a rare clinically heterogeneous type of NAGA deficiency (see this term) with developmental, neurologic and psychiatric manifestations presenting at an intermediate age.

ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY TYPE 3 Is also known as naga deficiency type 3|schindler disease type 3

• Intellectual disability
• Seizures
• Global developmental delay
• Strabismus
• Cataract

SOURCES: ORPHANET MENDELIAN

Combined D-2- and L-2-hydroxyglutaric aciduria (D-2-HG and L-2-HG) is an autosomal recessive neurometabolic disorder characterized by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Brain imaging shows abnormalities including enlarged ventricles, delayed myelination, and germinal layer cysts (summary by Muntau et al., 2000).See also isolated L-2-hydroxyglutaric aciduria (OMIM ) and isolated D-2-hydroxyglutaric aciduria (see {600721}).

• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Neoplasm

SOURCES: ORPHANET OMIM MENDELIAN

Congenital neutropenia-myelofibrosis-nephromegaly syndrome is rare, genetic, primary immunodeficiency disorder characterized by severe congenital neutropenia, bone marrow fibrosis and neutrophil dysfunction which is refractory to granulocyte colony-stimulating factor, manifesting with life-threatening infections and/or deep-seated abscesses, hepato-/splenomegaly, thrombocytopenia, hypergammaglobulinemia, anemia with reticulocytosis and nephromegaly. Other reported features include osteosclerosis and neurological abnormalities (e.g. developmental delay, cortical blindness, hearing loss, thin corpus callosum or dysrhythima on EEG).

CONGENITAL NEUTROPENIA-MYELOFIBROSIS-NEPHROMEGALY SYNDROME Is also known as vps45 deficiency|congenital neutropenia-bone marrow fibrosis-nephromegaly syndrome

• Global developmental delay
• Hearing impairment
• Failure to thrive
• Anemia
• Hepatomegaly

SOURCES: OMIM ORPHANET MENDELIAN

Alpha-N-acetylgalactosaminidase (NAGA) deficiency type 1 is a very rare and severe type of NAGA deficiency (see this term) characterized by infantile neuroaxonal dystrophy.

ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY TYPE 1 Is also known as schindler disease type 1|naga deficiency type 1

• Seizures
• Global developmental delay
• Hearing impairment
• Nystagmus
• Strabismus

SOURCES: ORPHANET MENDELIAN

A genetic disorder characterized by deficiency of the enzyme long-chain acyl-coenzyme A dehydrogenase that metabolizes long-chain fatty acids. Signs and symptoms appear in infancy or childhood and may be triggered during fasting, illness or exercise. They include hypoglycemia, muscle weakness and lethargy.

LONG CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY Is also known as lcad

• Generalized hypotonia
• Feeding difficulties
• Hepatomegaly
• Myopathy
• Vomiting

SOURCES: ORPHANET MENDELIAN

Inborn errors of mitochondrial fatty acid beta-oxidation include medium-chain acyl-CoA dehydrogenase deficiency (OMIM ), short-chain acyl-CoA dehydrogenase deficiency (OMIM ), and very long-chain acyl-CoA dehydrogenase deficiency.VLCAD deficiency can be classified clinically into 3 forms: a severe early-onset form with high incidence of cardiomyopathy and high mortality; an intermediate form with childhood onset, usually with hypoketotic hypoglycemia and more favorable outcome; and an adult-onset, myopathic form with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria after exercise or fasting (Andresen et al., 1999).Patients reported with long-chain acyl-CoA dehydrogenase (LCAD) deficiency before VLCAD deficiency was defined were later found to have VLCAD deficiency (Strauss et al., 1995; Roe and Ding, 2001).

ACYL-COA DEHYDROGENASE, VERY LONG-CHAIN, DEFICIENCY OF; ACADVLD Is also known as vlcad deficiency

• Generalized hypotonia
• Muscle weakness
• Muscular hypotonia
• Pain
• Hepatomegaly

SOURCES: OMIM MENDELIAN

• Seizures
• Neoplasm
• Muscle weakness
• Cleft palate
• Cryptorchidism

SOURCES: ORPHANET MENDELIAN

Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1 is a rare, inherited mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by intrauterine growth retardation, metabolic decompensation with recurrent vomiting, persistent severe lactic acidosis, encephalopathy, seizures, failure to thrive, severe global developmental delay, poor eye contact, severe muscular hypotonia or axial hypotonia with limb hypertonia, hepatomegaly and/or liver dysfunction and/or liver failure, leading to fatal outcome in severe cases. Neuroimaging abnormalities may include corpus callosum thinning, leukodystrophy, delayed myelination and basal ganglia involvement.

HEPATOENCEPHALOPATHY DUE TO COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 1 Is also known as hepatoencephalopathy, early fatal progressive|hepatoencephalopathy due to coxpd1

• Seizures
• Generalized hypotonia
• Microcephaly
• Growth delay
• Nystagmus

SOURCES: OMIM ORPHANET MESH MENDELIAN

Dihyropyrimidine dehydrogenase deficiency shows large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation in homozygous patients. In addition, homozygous and heterozygous mutation carriers can develop severe toxicity after the administration of the antineoplastic drug 5-fluorouracil (5FU), which is also catabolized by the DPYD enzyme. This is an example of a pharmacogenetic disorder (Van Kuilenburg et al., 1999).Since there is no correlation between genotype and phenotype in DPD deficiency, it appears that the deficiency is a necessary, but not sufficient, prerequisite for the development of clinical abnormalities (Van Kuilenburg et al., 1999; Enns et al., 2004).

DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY Is also known as pyrimidinemia, familial|familial pyrimidinemia|dpyd deficiency|dpd deficiency|thymine-uraciluria, hereditary

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: MESH OMIM ORPHANET MENDELIAN

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting the central nervous system.

• Seizures
• Short stature
• Microcephaly
• Scoliosis
• Ataxia

SOURCES: ORPHANET MENDELIAN