Delayed speech and language development, and Hepatomegaly

Medium match PYRIDOXINE-DEPENDENT EPILEPSY

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

Medium match VITAMIN B12-UNRESPONSIVE METHYLMALONIC ACIDEMIA TYPE MUT0

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: UMLS ORPHANET

Medium match BILE ACID SYNTHESIS DEFECT, CONGENITAL, 6; CBAS6

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Ataxia
• Hepatomegaly

SOURCES: DOID MONDO OMIM UMLS

Medium match GALACTOSE EPIMERASE DEFICIENCY

Epimerase-deficiency galactosemia was originally described as a benign condition in which GALE impairment is restricted to circulating red and white blood cells (Gitzelmann, 1972). Fibroblasts, liver, phytohemagglutinin-stimulated leukocyes, and Epstein Barr virus-transformed lymphoblasts from these patients all demonstrated normal or near-normal levels of GALE, leading to the designation 'peripheral' (or 'isolated') epimerase deficiency. A second form of epimerase deficiency became apparent in which a patient, despite normal GALT activity, presented with symptoms reminiscent of classic galactosemia and demonstrated severely impaired GALE activity in both red blood cells and fibroblasts (Holton et al., 1981). This form was designated 'generalized' epimerase deficiency. Openo et al. (2006) demonstrated that epimerase deficiency is in fact not a binary condition but is, rather, a continuum disorder.GALE encodes the third enzyme in the Leloir pathway of galactose metabolism. Galactosemia I is classic galactosemia (OMIM ), caused by deficiency of the second enzyme in the Leloir pathway, galactose-1-phosphate uridylyl-transferase (GALT ). Galactosemia II (OMIM ) is caused by deficiency of the first enzyme in the Leloir pathway, galactokinase (GALK ).

GALACTOSE EPIMERASE DEFICIENCY Is also known as gale deficiency, galactosemia iii, udp-galactose-4-epimerase deficiency

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET SCTID OMIM UMLS

Medium match JOUBERT SYNDROME 8; JBTS8

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: OMIM MESH MONDO DOID UMLS

Medium match MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2 WITH HYPERGLYCINEMIA; MMDS2

Multiple mitochondrial dysfunctions syndrome-2 (MMDS2) with hyperglycinemia is a severe autosomal recessive disorder characterized by developmental regression in infancy. Affected children have an encephalopathic disease course with seizures, spasticity, loss of head control, and abnormal movement. Additional more variable features include optic atrophy, cardiomyopathy, and leukodystrophy. Laboratory studies show increased serum glycine and lactate. Most patients die in childhood. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; {605899}), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including MMDS2, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014).For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (OMIM ).

MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2 WITH HYPERGLYCINEMIA; MMDS2 Is also known as ;bola3 deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: ORPHANET OMIM UMLS MONDO DOID

Medium match LONG CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY

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
• Myopathy
• Feeding difficulties
• Hepatomegaly
• Vomiting

SOURCES: UMLS ORPHANET

Medium match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 12; COXPD12

COXPD12 is an autosomal recessive mitochondrial neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability (summary by Steenweg et al., 2012).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 12; COXPD12 Is also known as leukoencephalopathy with thalamus and brainstem involvement and high lactate;ltbl;coxpd12; combined oxidative phosphorylation defect type 12; ltbl

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Failure to thrive

SOURCES: MONDO UMLS GARD ORPHANET OMIM

Medium match STOMATIN-DEFICIENT CRYOHYDROCYTOSIS WITH NEUROLOGIC DEFECTS; SDCHCN

Stomatin-deficient cryohydrocytosis with neurologic defects is an autosomal dominant disorder characterized by delayed psychomotor development, seizures, cataracts, and pseudohyperkalemia resulting from defects in the red blood cell membrane. The disorder combines the neurologic features of Glut1 deficiency syndrome-1 (GLUT1DS1 ), resulting from impaired glucose transport at the blood-brain barrier, and hemolytic anemia/pseudohyperkalemia with stomatocytosis, resulting from a cation leak in erythrocytes (summary by Bawazir et al., 2012).For a discussion of clinical and genetic heterogeneity of red cell stomatocyte disorders, see {194380}.

STOMATIN-DEFICIENT CRYOHYDROCYTOSIS WITH NEUROLOGIC DEFECTS; SDCHCN Is also known as glut1 deficiency syndrome with pseudohyperkalemia and hemolysis, cryohydrocytosis, stomatin-deficient, with mental retardation, seizures, cataracts, and massive hepatosplenomegaly;chc type 2; hereditary cryohydrocytosis type 2; stomatin-deficient cryohydrocytosis; sdchc

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: ORPHANET MONDO MESH OMIM UMLS

Medium match 3-METHYLGLUTACONIC ACIDURIA, TYPE I; MGCA1

Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: 1 with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). Genetic Heterogeneity and Classification of Methylglutaconic AciduriaMethylglutaconic aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA (MGCA2), also known as Barth syndrome (BTHS ), is caused by mutation in the tafazzin gene (TAZ ) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy, short stature, skeletal myopathy, and recurrent infections; cognitive development is normal. Type III MGCA (MGCA3 ), caused by mutation in the OPA3 gene (OMIM ) on chromosome 19q13, involves optic atrophy, movement disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate and 3-methylglutarate in urine are modest. Type IV MGCA (MGCA4 ) represents an unclassified group of patients who have severe psychomotor retardation and cerebellar dysgenesis. Type V MGCA (MGCA5 ), caused by mutation in the DNAJC19 gene (OMIM ) on chromosome 3q26, is characterized by early-onset dilated cardiomyopathy with conduction defects, nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Type VI MGCA (MGCA6 ), caused by mutation in the SERAC1 gene (OMIM ) on chromosome 6q25, includes deafness, encephalopathy, and a Leigh-like syndrome. Type VII MGCA (MGCA7 ), caused by mutation in the CLPB gene (OMIM ) on chromosome 11q13, includes cataracts, neurologic involvement, and neutropenia. Type VIII MCGA (MGCA8 ) is caused by mutation in the HTRA2 gene (OMIM ) on chromosome 2p13. Type IX MCGA (MGCA9 ) is caused by mutation in the TIMM50 gene (OMIM ) on chromosome 19q13.Eriguchi et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported in the literature as of 2003.Wortmann et al. (2013) proposed a pathomechanism-based classification for 'inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.'

3-METHYLGLUTACONIC ACIDURIA, TYPE I; MGCA1 Is also known as mga, type i;mga1, 3-methylglutaconyl-coa hydratase deficiency, 3-mg-coa-hydratase deficiency;3-methylglutaconyl-coa hydratase deficiency; 3mg-coa hydratase deficiency; mga1

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Microcephaly
• Ataxia

SOURCES: SCTID ORPHANET MONDO MESH OMIM NCIT UMLS GARD DOID