Liver transplant was ‘Trojan horse’ for baby’s variegate porphyria
Procedure unmasked girl's hidden genetic risk, case study shows
Written by |
An 11-month-old girl developed symptoms of variegate porphyria (VP) after receiving a liver transplant from her mother, according to a case report from Germany. The researchers said the case highlights how transplanted organs can sometimes carry hidden risks.
Both the child and her mother carried a mutation linked to VP, although the mother had never developed symptoms. The researchers said factors related to the transplant — including infections, medications, and stress — may have triggered the disease, leading to its unusually early onset.
The researchers said the liver transplant acted as a “Trojan horse,” triggering a previously silent genetic condition.
“We hope that our report will increase awareness of ‘rare risks’ for ‘rare diseases’ in liver transplantation,” they wrote.
The case report, “Liver graft as a ‘Trojan horse’: manifestation of variegate porphyria in an 11-month-old girl with biliary atresia after living-related liver transplantation,” was published in Gastroenterology Report.
VP makes rare early appearance
A type of porphyria, VP is typically caused by a mutation in one copy of the PPOX gene, which provides instructions for making an enzyme involved in heme production. Heme is a molecule that helps red blood cells carry oxygen. When this enzyme is deficient or not functional, the heme production pathway is disrupted, leading to a toxic buildup of porphyrins and their precursors.
The condition can cause light sensitivity, resulting in fragile skin and blistering, and, in some cases, may also lead to neurological symptoms. However, most people who carry the genetic mutation never develop symptoms of porphyria, and those who do usually experience the disease later in life.
In this case, the girl, who had biliary atresia (a condition that blocks bile flow from the liver), received part of her 37-year-old mother’s liver when she was six months old. She was then started on immunosuppressive therapy to prevent rejection.
Six weeks after the transplant, she developed several complications, including an episode of acute organ rejection, followed by bile duct narrowing and recurrent cholangitis (an infection of the bile ducts), all of which required additional treatment. Bile ducts are the channels that carry the digestive fluid bile from the liver to the intestines.
About five months after the transplant, the girl began to develop unusually fragile skin in areas exposed to light, such as the face and hands. Her symptoms worsened over the following months. She developed fluid-filled blisters that could easily rupture and leave slow-healing wounds.
As the condition progressed, other skin changes appeared, including small white cysts (milia), areas of darker pigmentation, scarring, and crusted lesions.
Because of these symptoms, doctors suspected cutaneous porphyria, a group of porphyrias that primarily affect the skin.
Laboratory testing confirmed a diagnosis of VP. Blood analyses showed a characteristic fluorescence pattern and elevated porphyrin levels, consistent with VP. Genetic testing identified a mutation in one copy of the PPOX gene in the child, her mother, and her maternal grandfather, none of whom had previously shown symptoms.
The researchers said stress, infections, and medications likely increased activity in the heme production pathway in the transplanted liver. This, in turn, unmasked the underlying enzyme deficiency, leading to the development of symptoms at an unusually early age.
At age 4, the girl’s growth and development are normal. She avoids sunlight when possible and uses protective measures such as wearing wide-brimmed hats and applying sunscreen. Her skin sensitivity has eased significantly over time. Blisters no longer appear, although some skin fragility persists, and sensitivity to light remains more noticeable in spring and summer than in winter.
The researchers said the case highlights the interaction between a previously unrecognized deficiency in the PPOX enzyme in the donated liver and factors in the recipient that together triggered the disease.
