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GRACILE syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

GRACILE Syndrome

GRACILE syndrome is a severe, rare genetic disorder characterized by growth retardation, liver dysfunction, and metabolic abnormalities that typically result in early death.

Overview

GRACILE syndrome is a severe disorder that begins before birth. The name is an acronym for the condition's characteristic features: growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death.

Infants with this condition experience slow growth before birth (intrauterine growth retardation) and are born smaller than average. After birth, they exhibit an inability to grow and gain weight at the expected rate, known as failure to thrive.

A hallmark of GRACILE syndrome is excess iron in the liver, which likely begins before birth. While iron levels may begin to improve after birth, they typically remain elevated. Within the first day of life, infants develop a buildup of lactic acid in the body (lactic acidosis). They also experience kidney problems that lead to an excess of amino acids in the urine (aminoaciduria).

Additionally, babies with GRACILE syndrome have cholestasis, a reduced ability to produce and release bile. This condition leads to irreversible liver disease (cirrhosis) in the first few months of life. Due to the severity of these health problems, infants with GRACILE syndrome do not survive for more than a few months, and about half die within a few days of birth.

Frequency

GRACILE syndrome is found almost exclusively in Finland, where it is estimated to affect 1 in 47,000 infants. At least 32 affected infants have been described in the medical literature.

Causes & Risk Factors

GRACILE syndrome is caused by a mutation in the BCS1L gene. The protein produced from this gene is found in mitochondria, which are cell structures that convert the energy from food into a form that cells can use. In mitochondria, the BCS1L protein plays a role in oxidative phosphorylation, a multistep process through which cells derive much of their energy.

The BCS1L protein is critical for the formation of complex III, one of several protein complexes involved in oxidative phosphorylation. The genetic change involved in GRACILE syndrome alters the BCS1L protein, causing the abnormal protein to be broken down more quickly than the normal protein. What little protein remains is able to help form some complete complex III, although the amount is severely reduced, particularly in the liver and kidneys.

As a result, complex III activity and oxidative phosphorylation are decreased in these organs. Without energy, these organs become damaged, leading to many of the features of GRACILE syndrome. It is not clear why a change in the BCS1L gene leads to iron accumulation in people with this condition.

Inheritance

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.

Other Names for This Condition

  • Fellman syndrome
  • Finnish lactic acidosis with hepatic hemosiderosis
  • Finnish lethal neonatal metabolic syndrome
  • Growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death

Frequently Asked Questions

Infants with GRACILE syndrome are typically born small for gestational age and exhibit failure to thrive after birth. Key physical features include a distinctive facial appearance with a prominent forehead and deep-set eyes, as well as signs of liver disease such as jaundice and hepatomegaly. The combination of growth retardation, liver dysfunction, and metabolic abnormalities like aminoaciduria and lactic acidosis is highly suggestive of GRACILE syndrome, prompting specific genetic testing for confirmation.
In GRACILE syndrome, iron overload begins prenatally and is primarily localized to the liver, leading to rapid and severe liver damage. Unlike hereditary hemochromatosis, which develops slowly over decades, the iron accumulation in GRACILE syndrome is acute and contributes to early liver cirrhosis. This rapid iron deposition, combined with cholestasis and lactic acidosis, accelerates liver failure and is a major contributor to the early mortality seen in affected infants.
Immediate priorities include managing lactic acidosis, which often presents within the first day of life, and addressing liver dysfunction. Medical teams typically provide supportive care, such as correcting acid-base imbalances and monitoring for signs of liver failure. Due to the rapid progression of the disease, care is often focused on comfort and managing acute metabolic crises rather than long-term curative treatments, as the condition is generally fatal within the first few months of life.
GRACILE syndrome is caused by a specific mutation in the SLC25A13 gene, and the high prevalence in Finland is attributed to the founder effect, where a small ancestral population carried the mutation. This geographic concentration means that genetic counseling for families in Finland is particularly important. Carrier testing is recommended for individuals of Finnish descent, and couples where both partners are carriers have a 25% chance of having an affected child in each pregnancy.
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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