MCID: MCR257
MIFTS: 27

Microcephaly, Amish Type

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Fetal diseases

Aliases & Classifications for Microcephaly, Amish Type

MalaCards integrated aliases for Microcephaly, Amish Type:

Name: Microcephaly, Amish Type 54 50 25 71 13 69
Amish Lethal Microcephaly 23 50 24 25 56 71 29
Mcpha 23 50 24 25 71
Amish Microcephaly 23 24 25

Characteristics:

Orphanet epidemiological data:

56
amish lethal microcephaly
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: late childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
progression of the disorder is precipitated by viral symptoms
death usually within first year of life
incidence of 1 in 480 among old order amish
carrier rate of 1 in 11 among old order amish


HPO:

32
microcephaly, amish type:
Mortality/Aging death in infancy
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Microcephaly, Amish Type

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 99742disease definitionamish lethal microcephaly is a very rare syndrome characterized by extreme microcephaly and early death, within the first year.epidemiologyit has been described only in the old order amish of lancaster county pennsylvania. in this population, birth prevalence is about 1/500.clinical descriptionmicrocephaly is a microcephalia vera (mv), evident at birth or through 22-week fetal ultrasound. affected children have high urinary levels of alpha-ketoglutaric acid.etiologyall affected infants are homozygous for the same mutation of the slc25a19 gene on chromosome 17 (17q25.3).genetic counselingthe condition follows an autosomal recessive pattern of inheritance.prognosisprognosis is very poor: the average life span of affected infants is between five and six months.visit the orphanet disease page for more resources. last updated: 12/31/2010

MalaCards based summary : Microcephaly, Amish Type, also known as amish lethal microcephaly, is related to microcephaly, and has symptoms including optic atrophy, ventriculomegaly and hepatomegaly. An important gene associated with Microcephaly, Amish Type is SLC25A19 (Solute Carrier Family 25 Member 19). Affiliated tissues include brain, cerebellum and pons.

Genetics Home Reference : 25 Amish lethal microcephaly is a disorder in which infants are born with a very small head and underdeveloped brain.

OMIM : 54
Amish type microcephaly is a severe autosomal recessive metabolic disorder characterized by severe microcephaly apparent at birth, profoundly delayed psychomotor development, brain malformations, and episodic encephalopathy associated with lactic acidosis and alpha-ketoglutaric aciduria (summary by Kelley et al., 2002). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270). (607196)

UniProtKB/Swiss-Prot : 71 Microcephaly, Amish type: A disorder characterized by severe congenital microcephaly and severe 2-ketoglutaric aciduria leading to death within the first year.

GeneReviews: NBK1365

Related Diseases for Microcephaly, Amish Type

Diseases related to Microcephaly, Amish Type via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 microcephaly 10.1

Symptoms & Phenotypes for Microcephaly, Amish Type

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Behavioral Psychiatric Manifestations:
irritability

Skeletal:
contractures

Head And Neck- Head:
microcephaly, extreme

Skeletal- Skull:
nearly absent cranial vault
absence of anterior and posterior fontanelles

Laboratory- Abnormalities:
increased urinary 2-ketoglutarate (variable)
increased urinary lactate

Head And Neck- Face:
micrognathia

Neurologic- Central Nervous System:
partial agenesis of the corpus callosum
limb hypertonia
truncal hypotonia
no psychomotor development
hypoplastic pons
more
Abdomen- Liver:
hepatomegaly associated with infection

Metabolic Features:
lactic acidosis during infection


Clinical features from OMIM:

607196

Human phenotypes related to Microcephaly, Amish Type:

56 32 (show all 31)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 optic atrophy 56 32 hallmark (90%) Very frequent (99-80%) HP:0000648
2 ventriculomegaly 56 32 frequent (33%) Frequent (79-30%) HP:0002119
3 hepatomegaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0002240
4 microcephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000252
5 metabolic acidosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001942
6 irritability 56 32 hallmark (90%) Very frequent (99-80%) HP:0000737
7 micrognathia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000347
8 sloping forehead 56 32 hallmark (90%) Very frequent (99-80%) HP:0000340
9 osteoporosis 56 32 frequent (33%) Frequent (79-30%) HP:0000939
10 agenesis of corpus callosum 56 32 frequent (33%) Frequent (79-30%) HP:0001274
11 spina bifida 56 32 frequent (33%) Frequent (79-30%) HP:0002414
12 lissencephaly 56 32 frequent (33%) Frequent (79-30%) HP:0001339
13 limb hypertonia 56 32 frequent (33%) Frequent (79-30%) HP:0002509
14 feeding difficulties 56 32 hallmark (90%) Very frequent (99-80%) HP:0011968
15 organic aciduria 56 32 hallmark (90%) Very frequent (99-80%) HP:0001992
16 decreased fetal movement 56 32 occasional (7.5%) Occasional (29-5%) HP:0001558
17 muscular hypotonia 56 32 frequent (33%) Frequent (79-30%) HP:0001252
18 cerebellar vermis hypoplasia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001320
19 generalized tonic-clonic seizures 56 32 occasional (7.5%) Occasional (29-5%) HP:0002069
20 decreased skull ossification 56 32 occasional (7.5%) Occasional (29-5%) HP:0004331
21 temperature instability 56 32 frequent (33%) Frequent (79-30%) HP:0005968
22 cleft soft palate 56 32 occasional (7.5%) Occasional (29-5%) HP:0000185
23 severe global developmental delay 56 32 hallmark (90%) Very frequent (99-80%) HP:0011344
24 limitation of joint mobility 56 32 occasional (7.5%) Occasional (29-5%) HP:0001376
25 cerebellar hypoplasia 32 HP:0001321
26 lactic acidosis 32 HP:0003128
27 partial agenesis of the corpus callosum 32 HP:0001338
28 death in infancy 56 Very frequent (99-80%)
29 progressive microcephaly 32 HP:0000253
30 flexion contracture 32 HP:0001371
31 muscular hypotonia of the trunk 32 HP:0008936

Drugs & Therapeutics for Microcephaly, Amish Type

Search Clinical Trials , NIH Clinical Center for Microcephaly, Amish Type

Genetic Tests for Microcephaly, Amish Type

Genetic tests related to Microcephaly, Amish Type:

id Genetic test Affiliating Genes
1 Amish Lethal Microcephaly 29 24 SLC25A19

Anatomical Context for Microcephaly, Amish Type

MalaCards organs/tissues related to Microcephaly, Amish Type:

39
Brain, Cerebellum, Pons

Publications for Microcephaly, Amish Type

Variations for Microcephaly, Amish Type

UniProtKB/Swiss-Prot genetic disease variations for Microcephaly, Amish Type:

71
id Symbol AA change Variation ID SNP ID
1 SLC25A19 p.Gly177Ala VAR_014103 rs119473030

ClinVar genetic disease variations for Microcephaly, Amish Type:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A19 NM_021734.4(SLC25A19): c.530G> C (p.Gly177Ala) single nucleotide variant Pathogenic rs119473030 GRCh37 Chromosome 17, 73274346: 73274346

Expression for Microcephaly, Amish Type

Search GEO for disease gene expression data for Microcephaly, Amish Type.

Pathways for Microcephaly, Amish Type

GO Terms for Microcephaly, Amish Type

Sources for Microcephaly, Amish Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
37 KEGG
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40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
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48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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