Amish, Mennonite, and Hutterite
Genetic Disorder Database

Microcephaly, Amish type

Disorder
OMIM #: #607196  (Click to access OMIM database)
Disorder: Microcephaly, Amish type 
Also known as: Amish lethal microcephaly
thiamine metabolism dysfunction syndrome 3 (THMD3) 
Clinical
Phenotype: extreme microcephaly, facial appearance similar to anencephaly, micrognathia, hepatomegaly, difficulty maintaining body temperature, lethargy, no psychomotor development, no gyral development, increased levels of 2-ketoglutarate and 2-ketoadipate in urine, sudden death 
Seen In: Amish
Old Order Mennonite
Old Colony Mennonite
Unknown/Other Mennonite
Hutterite
Remarks:

Testing is available at LHSC.

Autosomal recessive 

Mutations
1   Amish  
Gene: SLC25A19
Base Change: G>C, at nucleotide 530
Amino Acid Change: gly 177 --> ala
Last updated: 2022-11-07 

References
Kelley RI, Robinson D, Puffenberger EG, Strauss KA, Morton DH. (2002) Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria. Am J Med Genet Nov 1;112(4):318-26.
PubMed ID: 12376931 
Rosenberg M, Agarwala R, Bouffard G, Davis J, Fiermonte G, Hilliard M, Koch T, Kalikin F, Makalowska I, Morton D, Petty E, Weber J, Palmieri F, Kelley R, Schäffer A, Biesecker L. (2002) Mutant deoxynucleotide carrier is associated with congenital microcephaly. Nat Genet Sep;32(1):175-9.
PubMed ID: 12185364 
Siu VM, Ratko S, Prasad AN, Prasad C, Rupar CA. (2010) Amish microcephaly: Long-term survival and biochemical characterization. Am J Med Genet A Jul;152A(7):1747-51.
PubMed ID: 20583149 

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