A premature newborn in Japan was born to healthy parents through C-section. She also had a healthy older sister. Moreover, there was no significant medical history in the family. Her mother reported going to the hospital in her 31st week of pregnancy because the baby wasn’t growing well and wasn’t moving. The doctors decided to deliver the baby early at 32 weeks because of the poor fetal movements. When the baby was born, she needed help breathing and her Apgar scores were also low but improved quickly. Doctors took her to the Neonatal Intensive Care Unit. At birth, the baby weighed 995 grams, was 34 centimetres long, and had a head circumference of 26.7 centimetres.
To investigate the cause of the fetal growth restriction, doctors checked the infant for congenital TORCH infections (Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, varicella-zoster virus, and Treponema). However, they did not find any cause. They observed that the patient’s face was characteristic (hawk-nosed, micrognathia, interocular dissociation) and the cry was cat-like. The chromosome G-banding analysis and cytogenetic fluorescent in situ hybridization analysis showed that the infant had a karyotype of 46,XX,der(5)t(5;6)(p15.2;p22.3. The newborn’s parents agreed to undergo chromosome analysis after genetic counselling. Their chromosome analysis showed that the mother’s chromosome was normal, whereas the father’s chromosome showed reciprocal translocation as 46,XY,t(5;6)(p15.2;p22.3).
Diagnosis and Management
Doctors diagnosed the patient with patent ductus arteriosus (PDA) and left mild ventriculomegaly. They commenced tube feeding on day 1 after birth. The doctors treated her with indomethacin at 2, 3, 4, 7, 8, and 9 days old for hemodynamically significant PDA. The PDA closed at 21 days old and no side effects of indomethacin were detected. However, the levels of aspartate aminotransferase, gamma-glutamyl transpeptidase, and direct bilirubin gradually increased from birth. The infant excreted white stool at 15 days old.
Mutations in JAG1 on chromosome 20 or NOTCH2 on chromosome 1 are known to cause Allagile Syndrome. Therefore, doctors analysed the JAG1 and NOTCH sequences to detect mutations that can cause liver dysfunction. They found no such mutations. Doctors also analyzed the bile acids and they found no abnormal bile acids. They also performed magnetic resonance cholangiopancreatography (MRCP) to find out the aetiology of cholangiolitic hepatitis. Doctors found that the structures of the patient’s liver, gallbladder, and bile duct were normal, but there was a congenital portosystemic shunt. They treated the patient with ursodeoxycholic acid and phenobarbital, but her condition got worse after treatment. Furthermore, the PDA reopened when the patient was 25 days old
Since the cause of cholangiolitic hepatitis still wasn’t found, doctors took a sample of the liver to examine it. The results showed that the patient had cholestatic liver disease, which affected the portal triad. Doctors suspected it to be Alagille Syndrome. Unfortunately, the patient’s liver condition got worse, and she also had problems with blood clotting. The only way to treat it was through a liver transplant, so the doctors moved the patient for a liver transplant.
It was discovered that a specific type of chromosomal abnormality, called unbalanced reciprocal translocation between 5 and 6p, can cause a liver disorder called cholangiolitic hepatitis and a syndrome called Alagille Syndrome. The 5p syndrome is a genetic condition that occurs when part of chromosome 5 is missing, and it can cause developmental and intellectual disabilities. The 6p trisomy is another genetic condition where there is an extra copy of part of chromosome 6, and it can cause various physical and developmental problems.
They found that when these two genetic conditions are combined through unbalanced reciprocal translocation, it can result in liver problems and Alagille Syndrome. This disorder affects the liver, heart, eyes, and bones, and it can cause jaundice and obstruction of the bile ducts.
This patient had elevated levels of certain liver enzymes from birth, but imaging tests did not show any blockages in the bile ducts. Genetic testing also did not reveal any known genetic abnormalities. However, a liver biopsy confirmed the diagnosis of cholangiolitic hepatitis and this syndrome.
Alagille syndrome is a rare genetic disorder that affects many parts of the body, including the liver, heart, and bones. This condition is caused by a mutation in the JAG1 or NOTCH2 genes, which are responsible for the development of various organs during fetal development.
One of the most common symptoms of Alagille syndrome is liver disease, which can cause jaundice, itching, and other complications. In some cases, the liver disease can progress to cirrhosis, which can lead to liver failure.
In addition to liver problems, Alagille syndrome can also affect the heart, causing various defects that can lead to heart failure. Other symptoms of this condition include skeletal abnormalities, such as a butterfly-shaped vertebra or a shortened collarbone, as well as kidney problems, eye problems, and growth delays.
Diagnosing Alagille syndrome can be challenging, as there is no single test that can definitively confirm the condition. Instead, doctors may perform a variety of tests, including blood tests, imaging tests, and biopsies of the liver or other affected organs.
Treatment for Alagille syndrome is usually symptomatic. Since it is a genetic condition, there is no definitive cure at the moment. However, with early diagnosis and proper management, many people with this condition live normal lives. It is important for individuals with Alagille syndrome to work closely with their healthcare providers to manage their symptoms and prevent complications.
Up to 90% of patients with Alagille Syndrome have congenital heart disease, with peripheral pulmonic stenosis being the most common one. Other heart defects, skeletal abnormalities, and eye abnormalities can also be present.