Global developmental delay, and Abnormality of the liver

Combined oxidative phosphorylation defect type 21 is a rare mitochondrial disease characterized by axial hypotonia with limb hypertonia, developmental delay, hyperlactatemia, central nervous system anomalies visible on magnetic resonance imaging (e.g. corpus callosum hypoplasia, lesions of the globus pallidus) and multiple deficiency of the mitochondrial respiratory chain complexes in muscle tissue, but not in fibroblasts or liver.

COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 21 Is also known as coxpd21

• Global developmental delay
• Generalized hypotonia
• Hypoplasia of the corpus callosum
• Hypertonia
• Muscular hypotonia of the trunk

SOURCES: ORPHANET OMIM MENDELIAN

Pyridoxine-dependent epilepsy (PDE) is a rare neurometabolic disease characterized by recurrent intractable seizures in the prenatal, neonatal and postnatal period that are resistant to anti-epileptic drugs (AEDs) but that are responsive to pharmacological dosages of pyridoxine (vitamin B6).

PYRIDOXINE-DEPENDENT EPILEPSY Is also known as antiquitin deficiency|vitamin b6-dependent seizures

• Intellectual disability
• Seizures
• Global developmental delay
• Strabismus
• Muscular hypotonia

SOURCES: ORPHANET MENDELIAN

Vitamin B12-unresponsive methylmalonic acidemia type mut0 is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.

VITAMIN B12-UNRESPONSIVE METHYLMALONIC ACIDEMIA TYPE MUT0 Is also known as complete deficiency of methylmalonyl-coa mutase|vitamin b12-unresponsive methylmalonic aciduria type mut0

• Intellectual disability
• Global developmental delay
• Growth delay
• Muscular hypotonia
• Anemia

SOURCES: ORPHANET MENDELIAN

Dihydropteridine reductase (DHPR) deficiency is a severe form of hyperphenylalaninemia (HPA) due to impaired regeneration of tetrahydrobiopterin (BH4) (see this term), leading to decreased levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid, and causing neurological symptoms such as psychomotor delay, hypotonia, seizures, abnormal movements, hypersalivation, and swallowing difficulties.

DIHYDROPTERIDINE REDUCTASE DEFICIENCY Is also known as hyperphenylalaninemia due to dihydropteridine reductase deficiency|pku type 2|phenylketonuria type 2

• Intellectual disability
• Global developmental delay
• Microcephaly
• Dysphagia

SOURCES: ORPHANET MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Abnormal facial shape
• Cognitive impairment

SOURCES: OMIM MESH MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Microcephaly

SOURCES: OMIM MENDELIAN

Hemolytic anemia due to adenylate kinase deficiency is a rare hemolytic anemia due to an erythrocyte nucleotide metabolism disorder characterized by moderate to severe chronic nonspherocytic hemolytic anemia that may require regular blood transfusions and/or splenectomy and may be associated with psychomotor impairment.

• Global developmental delay
• Anemia
• Hepatosplenomegaly
• Hemolytic anemia
• Nonspherocytic hemolytic anemia

SOURCES: OMIM ORPHANET MESH MENDELIAN

GLYCOGEN STORAGE DISEASE VI; GSD6 Is also known as phosphorylase deficiency glycogen-storage disease of liver|hers disease|gsd vi

• Intellectual disability
• Global developmental delay
• Short stature
• Growth delay
• Failure to thrive

SOURCES: OMIM MENDELIAN

Glycogen storage disease type IX is a metabolic disorder resulting from a deficiency of hepatic phosphorylase kinase, a hexadecameric enzyme comprising 4 copies each of 4 unique subunits encoded by 4 different genes: alpha (PHKA2), beta (PHKB ), gamma (PHKG2 ), and delta (CALM1 ). Mutations within the PHKA2, PHKB, and PHKG2 genes result in GSD9A, GSD9B (OMIM ), and GSD9C (OMIM ), respectively. GSD IXa is an X-linked recessive disorder, whereas the others are autosomal recessive.GSD IXa has been further divided into types IXa1 (GSD9A1), with no PHK activity in liver or erythrocytes, and IXa2 (GSD9A2), with no PHK in liver, but normal activity in erythrocytes. The clinical presentation of both subtypes is the same, and both are caused by mutations in the PHKA2 gene. However, mutations that result in IXa2 are either missense or small in-frame deletions or insertions enabling residual enzyme expression in erythrocytes (Keating et al., 1985; Hendrickx et al., 1994; Beauchamp et al., 2007).See also X-linked muscle PHK deficiency (GSD9D ), caused by mutation in the gene encoding the muscle-specific alpha PHK subunit (PHKA1 ).

GLYCOGEN STORAGE DISEASE IXA1; GSD9A1 Is also known as glycogen storage disease viii, formerly|gsd8, formerly|gsd viii, formerly|liver glycogenosis, x-linked, type i|xlg1

• Intellectual disability
• Global developmental delay
• Short stature
• Growth delay
• Failure to thrive

SOURCES: OMIM MENDELIAN

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