Delayed speech and language development, and Choreoathetosis

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 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 58; MRT58

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: MONDO GARD OMIM UMLS

Medium match EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 37; EIEE37

Early infantile epileptic encephalopathy-37 is an autosomal recessive severe epileptic-dyskinetic disorder characterized by onset of intractable seizures or abnormal movements in the first years of life. Affected individuals show global developmental delay and/or developmental regression after onset of seizures. Patients also show a hyperkinetic movement disorder with choreoathetosis, spasticity, and rigidity. The individuals are severely affected, with mental retardation, absent speech, and impaired volitional movements (summary by Madeo et al., 2016).For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (OMIM ).

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

SOURCES: UMLS MONDO OMIM

Medium match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 13; COXPD13

Combined oxidative phosphorylation defect type 13 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by normal early development followed by the sudden onset in infancy of poor feeding, dysphagia, truncal (followed by global) hypotonia, motor regression, abnormal movements (i.e. severe dystonia of limbs, choreoathetosis, facial dyskinesias) and reduced tendon reflexes. The disease course is severe but nonprogressive.

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 13; COXPD13 Is also known as ;coxpd13

• Autosomal recessive inheritance
• Generalized hypotonia
• Growth delay
• Muscle weakness
• Myopathy

SOURCES: OMIM ORPHANET MONDO UMLS

Medium match WAISMAN SYNDROME; WSMN

Early-onset parkinsonism with intellectual deficit is a basal ganglia disorder characterised by parkinsonian-type symptoms (postural changes, tremor, rigidity), megalencephaly and variable intellectual deficit. Other signs are frontal bossing, persistent frontal lobe reflexes, strabismus and seizures. It has been described in three generations of one family. Transmission is X-linked, and the gene is located on chromosomal region Xq27.3-qter.

WAISMAN SYNDROME; WSMN Is also known as parkinsonism, early-onset, with mental retardation, basal ganglion disorder with mental retardation;bgmr, wsn;laxova-opitz syndrome; waisman syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Strabismus
• Cognitive impairment

SOURCES: OMIM MONDO MESH UMLS SCTID GARD ORPHANET

Medium match EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 25; EIEE25

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

SOURCES: OMIM MONDO GARD UMLS

Medium match STRIATONIGRAL DEGENERATION, INFANTILE; SNDI

Bilateral striatal necrosis (BSN) encompasses a heterogeneous group of neurologic disorders with different causation. Familial infantile striatal degeneration is rare and can be inherited as an autosomal recessive or mitochondrial (see {500003}) disorder. The familial form has an insidious onset and a slowly progressive course; the sporadic form is associated with acute systemic illness. Many features of BSN overlap with Leigh syndrome (OMIM ) and certain metabolic disorders, including glutaric acidemia I (OMIM ) and methylmalonic aciduria (OMIM ). See also Aicardi-Goutieres syndrome (OMIM ) (Mito et al., 1986; De Meirleir et al., 1995). Genetic Heterogeneity of Stiatonigral DegenerationChildhood-onset striatonigral degeneration (OMIM ) is caused by mutation in the VAC14 gene (OMIM ) on chromosome 16q22.See also adult-onset autosomal dominant striatal degeneration (ADSD ), caused by mutation in the PDE8B gene (OMIM ) on chromosome 5q13.

STRIATONIGRAL DEGENERATION, INFANTILE; SNDI Is also known as infantile bilateral striatal necrosis;ibsn, bilateral striatal necrosis, infantile, striatal degeneration, familial

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Ataxia
• Nystagmus

SOURCES: OMIM ORPHANET

Medium match EPISODIC ATAXIA TYPE 1

Episodic ataxia type 1 (EA1) is a frequent form of Hereditary episodic ataxia (EA; see this term) characterized by brief episodes of ataxia, neuromyotonia, and continuous interictal myokymia.

EPISODIC ATAXIA TYPE 1 Is also known as episodic ataxia with myokymia

• Scoliosis
• Motor delay
• Delayed speech and language development
• Dysarthria
• Cerebellar atrophy

SOURCES: ORPHANET

Medium match GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1

GLUT1 deficiency syndrome-1 is a neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. Onset of seizures, usually characterized by apneic episodes, staring spells, and episodic eye movements, occurs within the first 4 months of life. Other paroxysmal findings include intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe mental retardation. Hypoglycorrhachia (low CSF glucose, less than 40 mg/dl) and low CSF lactate are essentially diagnostic for the disorder. As more cases with GLUT1 deficiency syndrome were described, the phenotype was broadened to include individuals with ataxia and mental retardation but without seizures, individuals with dystonia and choreoathetosis, and rare individuals with absence seizures and no movement disorder. The disorder, which results from a defect in the GLUT1 glucose transporter causing decreased glucose concentration in the central nervous system, is part of a spectrum of neurologic phenotypes resulting from GLUT1 deficiency. GLUT deficiency syndrome-2 (OMIM ) represents the less severe end of the phenotypic spectrum and is associated with paroxysmal exercise-induced dystonia with or without seizures. Correct diagnosis of GLUT1 deficiency is important because a ketogenic diet often results in marked clinical improvement of the motor and seizure symptoms (reviews by Pascual et al., 2004 and Brockmann, 2009).

GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1 Is also known as glucose transport defect, blood-brain barrier;de vivo disease; glucose transporter type 1 deficiency; glut-1 deficiency syndrome; glut1-ds

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay

SOURCES: MESH ORPHANET OMIM GARD MONDO UMLS

Medium match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 32; COXPD32

Combined oxidative phosphorylation deficiency-32 is an autosomal recessive neurodegenerative disorder characterized by onset of delayed psychomotor development and developmental regression in infancy. Affected individuals have multiple variable symptoms, including poor or absent speech, inability to walk, and abnormal movements. Brain imaging shows T2-weighted abnormalities in the basal ganglia and brainstem consistent with Leigh syndrome (OMIM ). Patient cells showed decreased activities of mitochondrial respiratory chain complexes, I, III, and IV, as well as impaired mitochondrial translation (summary by Lake et al., 2017).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Scoliosis
• Nystagmus

SOURCES: OMIM