FamilyS Decade-Long Health Battle Ends with Rare Genetic Diagnosis
A Singaporean family’s years of suffering and misdiagnosis culminated in a breakthrough discovery: a rare genetic condition called haploinsufficiency of A20 (HA20). The diagnosis, initially for 18-year-old Nurul Naqisyah Mohamad Shahrel, unlocked answers for her father, Mohamad Shahrel hamid, 45, and her eight-year-old sister, Noura, offering a path toward treatment and preventing further health complications.
For decades, Mr. Shahrel endured unexplained fevers, ulcers, and diarrhea, navigating a frustrating cycle of hospital visits and symptom management. “I was a constant visitor to the hospital, but I was given medication for the symptoms, not the root cause,” he recalled. In July 2023, a tumor was discovered on his left thigh. Though,the tumor aggressively regrew,spreading to his knee,groin,and abdomen within two months. Faced with the agonizing prospect of amputation to save his life – a decision intricate by his responsibilities to his wife and five children – Mr. Shahrel underwent chemotherapy. Unfortunately, the treatment proved ineffective.
Dr.Lim Xin Rong, a senior consultant at TTSH’s department of rheumatology, allergy and immunology, identified the growth as a tenosynovial giant cell tumor, a rare condition affecting the lining of joints and tendons. While these tumors typically remain localized, Mr. Shahrel’s case was notably aggressive, spreading to his lymph nodes.
the situation worsened in November 2024 when Mr. Shahrel’s groin lymph nodes ruptured, causing severe bleeding and infection.This necessitated the removal of part of his pelvis along with his left leg in March 2025. “I lost all hope,” Mr. Shahrel admitted, especially as his daughters began exhibiting similar symptoms.
A turning point arrived when Ms. Nurul was admitted to KK Women’s and Children’s Hospital (KKH) in October 2024 with a persistent fever. Dr. Bianca Chan, a consultant with KKH’s rheumatology and immunology service, suspected a genetic autoinflammatory condition and swiftly ordered genetic testing. The results confirmed her suspicion: Ms. Nurul had HA20, a condition characterized by a deficiency in the A20 protein, leading to an overactive immune system and chronic inflammation.
“HA20 is a fairly new condition, recognized only recently as a disease entity,” Dr. Chan explained. “The first case was described in medical literature in 2016, and fewer than 200 cases have been reported worldwide as at July 2025.” She emphasized that even within a family carrying the same genetic mutation, symptom severity can vary. “The difficulty in making a diagnosis and the rarity of the condition explain why Mr. Shahrel’s family remained undiagnosed for so long despite him being symptomatic with recurrent ulcers; and Nurul (having the same) recurrent ulcers and fevers, and being admitted many times since March 2016, when she was eight years old.”
Dr. Lim underscored the importance of early diagnosis, stating, “A late diagnosis of HA20 leads to more suffering for the patients. They may go through years of struggling with unexplained health problems without a unifying diagnosis… Uncontrolled inflammation over time may cause irreversible damage to organs such as the joints, gut or kidneys.”
Following Ms. Nurul’s diagnosis, Mr. Shahrel underwent testing at TTSH and was also found to have HA20. While the connection between his HA20 and the tumor remains uncertain, the diagnosis provided a crucial framework for treatment. Noura, the youngest daughter, was later assessed and confirmed to carry the same mutation in January 2025, initiating her treatment shortly after. Doctors are optimistic that early intervention will prevent Noura from experiencing the prolonged suffering endured by her father and sister.
The two sisters are currently under the joint care of Dr. Chan and Dr. teh Kai liang at KKH. Ms. Nurul, who temporarily paused her studies to care for her father, expressed gratitude for the diagnosis and hopes to return to school to pursue her dream of becoming a physiotherapist. “Having watched what my father went through, including his amputation, I am thankful the doctors were able to identify my condition as well as that of my younger sister and stave off further onset,” she said, embodying a resilient spirit forged through years of uncertainty and hardship.
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