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Amish lethal microcephaly
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Amish lethal microcephaly

Amish lethal microcephaly is a severe metabolic disorder characterized by an unusually small head, brain underdevelopment, and limited life expectancy.

Overview

Amish lethal microcephaly is a disorder in which infants are born with an unusually small head (microcephaly) and an underdeveloped brain.

Symptoms

  • Physical Features: Sloping forehead, extremely small head size, unusually small lower jaw and chin (micrognathia), and an enlarged liver (hepatomegaly).
  • Neurological and Metabolic: Seizures, difficulty maintaining body temperature, and irritability starting in the second or third month of life.
  • Biochemical: Presence of alpha-ketoglutaric acid in the urine (alpha-ketoglutaric aciduria) and a tendency to develop elevated levels of acid in the blood and tissues (metabolic acidosis) during viral illnesses.
  • Developmental: Infants typically feed adequately but do not develop skills such as purposeful movement or the ability to track faces and sounds.

Causes

Mutations in the SLC25A19 gene cause this condition. This gene produces a protein that transports thiamine pyrophosphate into the mitochondria. This transport is essential for the activity of mitochondrial enzymes, including the alpha-ketoglutarate dehydrogenase complex. A specific mutation (Gly177Ala) interferes with this transport, leading to abnormal brain development.

Inheritance

This condition is inherited in an autosomal recessive pattern. Both parents of an affected individual carry one copy of the mutated gene but typically do not exhibit symptoms. Affected infants typically live only about six months.

Frequently Asked Questions

Infants with Amish lethal microcephaly usually survive only about six months. Palliative care teams can provide comfort measures, pain control, seizure management, and support for feeding and respiratory needs. Early involvement of hospice or home‑care services ensures a dignified and symptom‑free end‑of‑life experience for both the child and family.
Both parents can undergo targeted genetic testing for the Gly177Ala mutation in the SLC25A19 gene. If one or both are carriers, a detailed risk assessment can be performed, and options such as preimplantation genetic diagnosis (PGD) or prenatal testing via chorionic villus sampling or amniocentesis can be discussed. Early identification allows for informed reproductive choices and preparation for specialized neonatal care.
Management focuses on frequent monitoring of blood pH and bicarbonate levels, especially during infections. Oral or intravenous sodium bicarbonate may be administered to correct acidosis. Maintaining adequate hydration, avoiding prolonged fasting, and promptly treating fevers with antipyretics help reduce metabolic stress. Regular metabolic panels and urine organic acid analysis guide therapy adjustments.
Within the first few weeks of life, infants may exhibit an extremely small head circumference, a sloping forehead, micrognathia (small lower jaw), and hepatomegaly (enlarged liver). Seizures often appear between 2–3 months, accompanied by difficulty maintaining body temperature and irritability. Urine testing may reveal alpha‑ketoglutaric aciduria, and blood gas analysis can show metabolic acidosis, especially during viral illnesses.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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