MCID: MCR257
MIFTS: 28

Microcephaly, Amish Type

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

Aliases & Classifications for Microcephaly, Amish Type

MalaCards integrated aliases for Microcephaly, Amish Type:

Name: Microcephaly, Amish Type 53 49 24 71 36 13 69
Amish Lethal Microcephaly 53 23 49 24 55 71 28
Mcpha 53 23 49 24 71
Amish Microcephaly 23 24
Thiamine Metabolism Dysfunction Syndrome 3 ; Thmd3 53
Thiamine Metabolism Dysfunction Syndrome 3 53
Thmd3 53

Characteristics:

Orphanet epidemiological data:

55
amish lethal microcephaly
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: late childhood;

OMIM:

53
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:

31
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 : 49 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 agenesis of corpus callosum, muscular hypotonia 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 : 24 Amish lethal microcephaly is a disorder in which infants are born with a very small head and underdeveloped brain.

OMIM : 53 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:

# Related Disease Score Top Affiliating Genes
1 microcephaly 10.1

Symptoms & Phenotypes for Microcephaly, Amish Type

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Face:
micrognathia

Neurologic Central Nervous System:
partial agenesis of the corpus callosum
limb hypertonia
hypoplastic cerebellum
truncal hypotonia
no psychomotor development
more
Laboratory Abnormalities:
increased urinary lactate
increased urinary 2-ketoglutarate (variable)

Abdomen Liver:
hepatomegaly associated with infection

Metabolic Features:
lactic acidosis during infection

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


Clinical features from OMIM:

607196

Human phenotypes related to Microcephaly, Amish Type:

55 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 55 31 frequent (33%) Frequent (79-30%) HP:0001274
2 muscular hypotonia 55 31 frequent (33%) Frequent (79-30%) HP:0001252
3 hepatomegaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0002240
4 microcephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000252
5 optic atrophy 55 31 hallmark (90%) Very frequent (99-80%) HP:0000648
6 osteoporosis 55 31 frequent (33%) Frequent (79-30%) HP:0000939
7 micrognathia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000347
8 irritability 55 31 hallmark (90%) Very frequent (99-80%) HP:0000737
9 feeding difficulties 55 31 hallmark (90%) Very frequent (99-80%) HP:0011968
10 severe global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0011344
11 limitation of joint mobility 55 31 occasional (7.5%) Occasional (29-5%) HP:0001376
12 generalized tonic-clonic seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0002069
13 ventriculomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0002119
14 spina bifida 55 31 frequent (33%) Frequent (79-30%) HP:0002414
15 decreased fetal movement 55 31 occasional (7.5%) Occasional (29-5%) HP:0001558
16 metabolic acidosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001942
17 sloping forehead 55 31 hallmark (90%) Very frequent (99-80%) HP:0000340
18 lissencephaly 55 31 frequent (33%) Frequent (79-30%) HP:0001339
19 decreased skull ossification 55 31 occasional (7.5%) Occasional (29-5%) HP:0004331
20 cerebellar vermis hypoplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001320
21 limb hypertonia 55 31 frequent (33%) Frequent (79-30%) HP:0002509
22 organic aciduria 55 31 hallmark (90%) Very frequent (99-80%) HP:0001992
23 temperature instability 55 31 frequent (33%) Frequent (79-30%) HP:0005968
24 cleft soft palate 55 31 occasional (7.5%) Occasional (29-5%) HP:0000185
25 flexion contracture 31 HP:0001371
26 death in infancy 55 Very frequent (99-80%)
27 lactic acidosis 31 HP:0003128
28 cerebellar hypoplasia 31 HP:0001321
29 partial agenesis of the corpus callosum 31 HP:0001338
30 muscular hypotonia of the trunk 31 HP:0008936
31 progressive microcephaly 31 HP:0000253

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:

# Genetic test Affiliating Genes
1 Amish Lethal Microcephaly 28 SLC25A19

Anatomical Context for Microcephaly, Amish Type

MalaCards organs/tissues related to Microcephaly, Amish Type:

38
Brain, Cerebellum, Pons

Publications for Microcephaly, Amish Type

Articles related to Microcephaly, Amish Type:

# Title Authors Year
1
Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria. ( 12376931 )
2002
2
Amish Lethal Microcephaly ( 20301539 )
1993

Variations for Microcephaly, Amish Type

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

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

ClinVar genetic disease variations for Microcephaly, Amish Type:

6
# 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
27 GO
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29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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42 MESH via Orphanet
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50 NINDS
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54 OMIM via Orphanet
58 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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