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 57 53 25 75 37 13 40 73
Amish Lethal Microcephaly 57 24 53 25 59 75 29 6
Mcpha 57 24 53 25 75
Amish Microcephaly 24 25
Thiamine Metabolism Dysfunction Syndrome 3 ; Thmd3 57
Thiamine Metabolism Dysfunction Syndrome 3 57
Thmd3 57

Characteristics:

Orphanet epidemiological data:

59
amish lethal microcephaly
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: late childhood;

OMIM:

57
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 : 53 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.

MalaCards based summary : Microcephaly, Amish Type, also known as amish lethal microcephaly, is related to microcephaly. An important gene associated with Microcephaly, Amish Type is SLC25A19 (Solute Carrier Family 25 Member 19). Affiliated tissues include brain, cerebellum and pons, and related phenotypes are agenesis of corpus callosum and muscular hypotonia

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

OMIM : 57 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 : 75 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:

57
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:

59 32 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 59 32 frequent (33%) Frequent (79-30%) HP:0001274
2 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
3 hepatomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0002240
4 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
5 optic atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000648
6 osteoporosis 59 32 frequent (33%) Frequent (79-30%) HP:0000939
7 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
8 irritability 59 32 hallmark (90%) Very frequent (99-80%) HP:0000737
9 feeding difficulties 59 32 hallmark (90%) Very frequent (99-80%) HP:0011968
10 severe global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0011344
11 limitation of joint mobility 59 32 occasional (7.5%) Occasional (29-5%) HP:0001376
12 generalized tonic-clonic seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0002069
13 ventriculomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0002119
14 spina bifida 59 32 frequent (33%) Frequent (79-30%) HP:0002414
15 decreased fetal movement 59 32 occasional (7.5%) Occasional (29-5%) HP:0001558
16 metabolic acidosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001942
17 sloping forehead 59 32 hallmark (90%) Very frequent (99-80%) HP:0000340
18 lissencephaly 59 32 frequent (33%) Frequent (79-30%) HP:0001339
19 decreased skull ossification 59 32 occasional (7.5%) Occasional (29-5%) HP:0004331
20 cerebellar vermis hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001320
21 limb hypertonia 59 32 frequent (33%) Frequent (79-30%) HP:0002509
22 organic aciduria 59 32 hallmark (90%) Very frequent (99-80%) HP:0001992
23 temperature instability 59 32 frequent (33%) Frequent (79-30%) HP:0005968
24 cleft soft palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000185
25 flexion contracture 32 HP:0001371
26 death in infancy 59 Very frequent (99-80%)
27 lactic acidosis 32 HP:0003128
28 cerebellar hypoplasia 32 HP:0001321
29 partial agenesis of the corpus callosum 32 HP:0001338
30 muscular hypotonia of the trunk 32 HP:0008936
31 progressive microcephaly 32 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 29 SLC25A19

Anatomical Context for Microcephaly, Amish Type

MalaCards organs/tissues related to Microcephaly, Amish Type:

41
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:

75
# Symbol AA change Variation ID SNP ID
1 SLC25A19 p.Gly177Ala VAR_014103 rs119473030

ClinVar genetic disease variations for Microcephaly, Amish Type:

6
(show all 30)
# 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
2 SLC25A19 NM_021734.4(SLC25A19): c.530G> C (p.Gly177Ala) single nucleotide variant Pathogenic rs119473030 GRCh38 Chromosome 17, 75278265: 75278265
3 SLC25A19 NM_021734.4(SLC25A19): c.135T> A (p.Leu45=) single nucleotide variant Uncertain significance rs373190423 GRCh37 Chromosome 17, 73282538: 73282538
4 SLC25A19 NM_021734.4(SLC25A19): c.135T> A (p.Leu45=) single nucleotide variant Uncertain significance rs373190423 GRCh38 Chromosome 17, 75286457: 75286457
5 SLC25A19 NM_021734.4(SLC25A19): c.483C> T (p.Ala161=) single nucleotide variant Conflicting interpretations of pathogenicity rs142281464 GRCh37 Chromosome 17, 73274393: 73274393
6 SLC25A19 NM_021734.4(SLC25A19): c.483C> T (p.Ala161=) single nucleotide variant Conflicting interpretations of pathogenicity rs142281464 GRCh38 Chromosome 17, 75278312: 75278312
7 SLC25A19 NM_021734.4(SLC25A19): c.797T> G (p.Met266Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs148372053 GRCh37 Chromosome 17, 73269698: 73269698
8 SLC25A19 NM_021734.4(SLC25A19): c.797T> G (p.Met266Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs148372053 GRCh38 Chromosome 17, 75273617: 75273617
9 SLC25A19 NM_021734.4(SLC25A19): c.*200G> A single nucleotide variant Uncertain significance rs62622012 GRCh38 Chromosome 17, 75273251: 75273251
10 SLC25A19 NM_021734.4(SLC25A19): c.*200G> A single nucleotide variant Uncertain significance rs62622012 GRCh37 Chromosome 17, 73269332: 73269332
11 SLC25A19 NM_021734.4(SLC25A19): c.324C> G (p.His108Gln) single nucleotide variant Uncertain significance rs146573563 GRCh38 Chromosome 17, 75283558: 75283558
12 SLC25A19 NM_021734.4(SLC25A19): c.324C> G (p.His108Gln) single nucleotide variant Uncertain significance rs146573563 GRCh37 Chromosome 17, 73279639: 73279639
13 SLC25A19 NM_021734.4(SLC25A19): c.246C> T (p.His82=) single nucleotide variant Conflicting interpretations of pathogenicity rs535476833 GRCh38 Chromosome 17, 75286346: 75286346
14 SLC25A19 NM_021734.4(SLC25A19): c.246C> T (p.His82=) single nucleotide variant Conflicting interpretations of pathogenicity rs535476833 GRCh37 Chromosome 17, 73282427: 73282427
15 SLC25A19 NM_021734.4(SLC25A19): c.*274C> G single nucleotide variant Likely benign rs7198 GRCh38 Chromosome 17, 75273177: 75273177
16 SLC25A19 NM_021734.4(SLC25A19): c.*274C> G single nucleotide variant Likely benign rs7198 GRCh37 Chromosome 17, 73269258: 73269258
17 SLC25A19 NM_021734.4(SLC25A19): c.*113G> C single nucleotide variant Uncertain significance rs780528476 GRCh38 Chromosome 17, 75273338: 75273338
18 SLC25A19 NM_021734.4(SLC25A19): c.*113G> C single nucleotide variant Uncertain significance rs780528476 GRCh37 Chromosome 17, 73269419: 73269419
19 SLC25A19 NM_021734.4(SLC25A19): c.930C> A (p.Phe310Leu) single nucleotide variant Uncertain significance rs886053391 GRCh38 Chromosome 17, 75273484: 75273484
20 SLC25A19 NM_021734.4(SLC25A19): c.930C> A (p.Phe310Leu) single nucleotide variant Uncertain significance rs886053391 GRCh37 Chromosome 17, 73269565: 73269565
21 SLC25A19 NM_021734.4(SLC25A19): c.-153_-150delAGAG deletion Likely benign rs796850773 GRCh38 Chromosome 17, 75289391: 75289394
22 SLC25A19 NM_021734.4(SLC25A19): c.-153_-150delAGAG deletion Likely benign rs796850773 GRCh37 Chromosome 17, 73285472: 73285475
23 SLC25A19 NM_021734.4(SLC25A19): c.-201T> A single nucleotide variant Uncertain significance rs576181366 GRCh38 Chromosome 17, 75289442: 75289442
24 SLC25A19 NM_021734.4(SLC25A19): c.-201T> A single nucleotide variant Uncertain significance rs576181366 GRCh37 Chromosome 17, 73285523: 73285523
25 SLC25A19 NM_021734.4(SLC25A19): c.*437T> G single nucleotide variant Likely benign rs73356384 GRCh38 Chromosome 17, 75273014: 75273014
26 SLC25A19 NM_021734.4(SLC25A19): c.*437T> G single nucleotide variant Likely benign rs73356384 GRCh37 Chromosome 17, 73269095: 73269095
27 SLC25A19 NM_021734.4(SLC25A19): c.20A> G (p.Lys7Arg) single nucleotide variant Uncertain significance rs762770947 GRCh38 Chromosome 17, 75286745: 75286745
28 SLC25A19 NM_021734.4(SLC25A19): c.20A> G (p.Lys7Arg) single nucleotide variant Uncertain significance rs762770947 GRCh37 Chromosome 17, 73282826: 73282826
29 SLC25A19 NM_021734.4(SLC25A19): c.-139T> G single nucleotide variant Likely benign rs2291033 GRCh38 Chromosome 17, 75289380: 75289380
30 SLC25A19 NM_021734.4(SLC25A19): c.-139T> G single nucleotide variant Likely benign rs2291033 GRCh37 Chromosome 17, 73285461: 73285461

Expression for Microcephaly, Amish Type

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Pathways for Microcephaly, Amish Type

GO Terms for Microcephaly, Amish Type

Sources for Microcephaly, Amish Type

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74 UMLS via Orphanet
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