Amish Lethal Microcephaly

Amish lethal microcephaly is a disorder in which infants are born with a very small head and underdeveloped brain.
Infants with Amish lethal microcephaly have an irregular forehead, jaw and chin size. The overall size of their skull is significantly smaller than a child born without the disorder. Liver problems have also been known to arise from the condition.
Affected infants are known to have difficulty maintaining their ideal body temperature and can commonly have regular seizures. The infants begin to become endowed with the effects of the conditions at around the two to three month stage of life. A compound called alpha-ketoglutaric acid can be detected in their urine and during episodes of viral illness they tend to develop elevated levels of acid in the blood and tissues. They are able to feed adequately, however their motor skills, balance and reactions to movement and sound are greatly hindered. Affected infants live only to roughly six months.

A mutation in the SLC25A19 gene causes Amish lethal microcephaly.
The SLC25A19 gene ultimately produces a protein that is a member of the solute carrier family of proteins. The protein produced from the SLC25A19 gene transports a molecule called thiamine pyrophosphate into the mitochondria. This compound is involved in the activity of a group of mitochondrial enzymes called the dehydrogenase complexes. The transport of thiamine pyrophosphate into the mitochondria is believed to be important in brain development.
All known individuals with Amish lethal microcephaly have a mutation in which the protein building block (amino acid) alanine is substituted for the amino acid glycine at position 177 of the SLC25A19 protein. Researchers believe that this mutation interferes with the transport of thiamine pyrophosphate into the mitochondria resulting in the abnormal brain development and alpha-ketoglutaric aciduria seen in Amish lethal microcephaly.
This condition is inherited in an autosomal recessive pattern. (i.e. both copies of the gene in each cell have mutations.) The parents of an individual with an autosomal recessive condition each bear one copy of the mutated gene, but do not show symptoms of the condition.