Delayed speech and language development, and Memory impairment

Medium match CRIGLER-NAJJAR SYNDROME TYPE 1

Crigler-Najjar syndrome type 1 (CNS1) is the most severe form of CNS (see this term), a hereditary disorder of hepatic bilirubin conjugation, characterized by severe neonatal unconjugated hyperbilirubinemia due to a complete absence of hepatic bilirubin glucuronosyltransferase (BGT).

CRIGLER-NAJJAR SYNDROME TYPE 1 Is also known as bilirubin uridinediphosphate glucuronosyltransferase deficiency type 1; bilirubin-ugt deficiency type 1; hereditary unconjugated hyperbilirubinemia type 1; ugt deficiency type 1

• Intellectual disability
• Seizures
• Hearing impairment
• Delayed speech and language development
• Tremor

SOURCES: ORPHANET SCTID

Medium match HUNTINGTON DISEASE-LIKE 1; HDL1

HUNTINGTON DISEASE-LIKE 1; HDL1 Is also known as huntington-like neurodegenerative disorder 1;hln1, huntington-like neurodegenerative disorder, autosomal dominant, prion disease, early-onset, with prominent psychiatric features;early-onset prion disease with prominent psychiatric features; hdl1

• Autosomal dominant inheritance
• Seizures
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: UMLS OMIM MONDO ORPHANET DOID MESH

Medium match CEROID LIPOFUSCINOSIS, NEURONAL, 7; CLN7

The neuronal ceroid lipofuscinoses (NCL, or CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally (summary by Mole et al., 2005).For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (OMIM ).

CEROID LIPOFUSCINOSIS, NEURONAL, 7; CLN7 Is also known as ;

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Ataxia
• Visual impairment

SOURCES: OMIM MONDO MESH GARD DOID UMLS ORPHANET

Medium match ACERULOPLASMINEMIA

Aceruloplasminemia is an adult-onset disorder of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.

ACERULOPLASMINEMIA Is also known as ;hereditary ceruloplasmin deficiency

• Autosomal recessive inheritance
• Ataxia
• Anemia
• Delayed speech and language development
• Dysarthria

SOURCES: GARD SCTID UMLS OMIM MONDO DOID ORPHANET

Medium match CEREBELLAR ATAXIA, NONPROGRESSIVE, WITH MENTAL RETARDATION; CANPMR

Nonprogressive cerebellar ataxia with mental retardation is an autosomal dominant neurodevelopmental disorder characterized by mildly delayed psychomotor development, early onset of cerebellar ataxia, and intellectual disability later in childhood and adult life. Other features may include neonatal hypotonia, dysarthria, and dysmetria. Brain imaging in some patients shows cerebellar atrophy. Dysmorphic facial features are variable (summary by Thevenon et al., 2012).

CEREBELLAR ATAXIA, NONPROGRESSIVE, WITH MENTAL RETARDATION; CANPMR Is also known as ;

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

SOURCES: MONDO DOID UMLS OMIM ORPHANET

Medium match LIPOID PROTEINOSIS OF URBACH AND WIETHE

Lipoid proteinosis of Urbach and Wiethe is a rare autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. The disorder is clinically heterogeneous, with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurologic abnormalities such as temporal lobe epilepsy. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane (summary by Hamada et al., 2002 and Hamada et al., 2003).

LIPOID PROTEINOSIS OF URBACH AND WIETHE Is also known as lipoid proteinosis, urbach-wiethe disease, hyalinosis cutis et mucosae;hyalinosis cutis et mucosae; urbach-wiethe disease

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Pica
• High palate

SOURCES: SCTID MESH GARD DOID OMIM NCIT UMLS ORPHANET MONDO

Medium match LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM

Vanishing white matter leukodystrophy is an autosomal recessive neurologic disorder characterized by variable neurologic features, including progressive cerebellar ataxia, spasticity, and cognitive impairment associated with white matter lesions on brain imaging. The age at onset can range from early infancy to adulthood. Rapid neurologic deterioration can occur following minor head trauma. Female mutation carriers may develop ovarian failure, manifest as primary amenorrhea or as secondary amenorrhea lasting more than 6 months, associated with elevated gonadotropin levels at age less than 40 years (summary by Van der Knaap et al., 1998 and Schiffmann et al., 1997).

LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM Is also known as childhood ataxia with central nervous system hypomyelinization;cach, vanishing white matter leukodystrophy, cree leukoencephalopathy;cle

• Autosomal recessive inheritance
• Seizures
• Generalized hypotonia
• Pica
• Ataxia

SOURCES: ORPHANET OMIM

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

Medium match NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4; NBIA4

Neurodegeneration with brain iron accumulation-4 (NBIA4) is an autosomal recessive neurodegenerative disorder characterized by progressive spastic paraplegia, parkinsonism unresponsive to L-DOPA treatment, and psychiatric or behavioral symptoms. Other neurologic features, including optic atrophy, eye movement abnormalities, dystonia, dysphagia, dysarthria, and motor axonal neuropathy, may occur. Brain MRI shows T2-weighted hypointensities in the globus pallidus and substantia nigra. Onset is usually in the first 2 decades, but later onset has been reported (summary by Dogu et al., 2013). There is phenotypic variation: some patients may not have extrapyramidal signs and may have muscle weakness and atrophy as well as cognitive impairment or developmental delay (Deschauer et al., 2012)For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (OMIM ).

NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4; NBIA4 Is also known as mitochondrial protein-associated neurodegeneration;mpan;mpan; nbia due to c19orf12 mutation; nbia4; neurodegeneration with brain iron accumulation due to c19orf12 mutation; neurodegeneration with brain iron accumulation type 4

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

SOURCES: OMIM DOID SCTID GARD UMLS ORPHANET MONDO

Medium match SIALURIA

Sialuria is an extremely rare metabolic disorder described in fewer than 10 patients to date and characterized by variable signs and symptoms, mostly in infancy, including transient failure to thrive, slightly prolonged neonatal jaundice, equivocal or mild hepatomegaly, microcytic anemia, frequent upper respiratory infections, gastroenteritis, dehydration and flat and coarse facies. Learning difficulties and seizures may occur in childhood.

SIALURIA Is also known as sialuria, french type;sialuria, french type

• Autosomal dominant inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Scoliosis

SOURCES: OMIM GARD MONDO ORPHANET DOID