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Amish lethal microcephaly
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Reviewed July 2013
What is 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 a sloping forehead and an extremely small head size. They may also have an unusually small lower jaw and chin (micrognathia) and an enlarged liver (hepatomegaly).
Affected infants may have seizures and difficulty maintaining their body temperature. Often they become very irritable starting in the second or third month of life. A compound called alpha-ketoglutaric acid can be detected in their urine (alpha-ketoglutaric aciduria), and during episodes of viral illness they tend to develop elevated levels of acid in the blood and tissues (metabolic acidosis). Infants with this disorder typically feed adequately but do not develop skills such as purposeful movement or the ability to track faces and sounds. Affected infants live only about six months.
How common is Amish lethal microcephaly?
Amish lethal microcephaly occurs in approximately 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population.
What genes are related to Amish lethal microcephaly?
Mutations in the SLC25A19 gene cause Amish lethal microcephaly.
The SLC25A19 gene provides instructions for producing a protein that is a member of the solute carrier (SLC) family of proteins. Proteins in the SLC family transport various compounds across the membranes surrounding the cell and its component parts. The protein produced from the SLC25A19 gene transports a molecule called thiamine pyrophosphate into the mitochondria, the energy-producing centers of cells. This compound is involved in the activity of a group of mitochondrial enzymes called the dehydrogenase complexes, one of which is the alpha-ketoglutarate dehydrogenase complex. 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, written as Gly177Ala or G177A. Researchers believe that this mutation interferes with the transport of thiamine pyrophosphate into the mitochondria and the activity of the alpha-ketoglutarate dehydrogenase complex, resulting in the abnormal brain development and alpha-ketoglutaric aciduria seen in Amish lethal microcephaly.
Read more about the SLC25A19 gene.
How do people inherit Amish lethal microcephaly?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about diagnosis or management of Amish lethal microcephaly?
These resources address the diagnosis or management of Amish lethal microcephaly and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about Amish lethal microcephaly?
You may find the following resources about Amish lethal microcephaly helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for Amish lethal microcephaly?
What if I still have specific questions about Amish lethal microcephaly?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding Amish lethal microcephaly?
acidosis ; aciduria ; amino acid ; autosomal ; autosomal recessive ; carrier ; cell ; compound ; dehydrogenase ; gene ; glycine ; microcephaly ; micrognathia ; mitochondria ; molecule ; mutation ; population ; protein ; recessive ; solute ; thiamine
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (7 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.