Gaucher disease may have very distinct manifestations, even among genetically similar people with the same mutation in the GBA gene. Early diagnosis and treatment are key to avoid severe consequences of the condition, a case report suggests.
The study, “Two siblings with Gaucher type 3c: different clinical presentations,” was published in the Journal of Pediatric Endocrinology and Metabolism.
Gaucher disease is a genetic disorder caused by mutations in the GBA gene, which holds the instructions to produce the enzyme beta-glucocerebrosidase. Malfunction of this enzyme leads to excessive accumulation of lipids in the cells of different organs.
The disorder is divided into three types, depending on whether there are symptoms in the nervous system, and each of these types is further classified depending on the most commonly affected organ.
Type 3c Gaucher is characterized by heart damage and formation of calcium deposits in the heart, which makes the muscles more rigid and impairs blood pumping.
Researchers in Turkey described the cases of two sisters, daughters of a consanguineous marriage between first cousins, who developed Gaucher type 3c but had different symptoms.
The first patient was a 6-month-old girl, who presented with progressive liver disease and a yellow tone to her skin (jaundice). She had been diagnosed with an enlarged liver and spleen when she was 40 days old.
Lab tests showed anemia and low platelet count, the presence of bilirubin in the blood, and high levels of transaminase and other liver enzymes, which indicate liver damage.
The girl received a liver transplant from her mother; the extracted liver showed scarred tissue and signs of damage. The doctors performed a genetic test and discovered that the patient had a mutation called D448H — the most common mutation associated with type 3c Gaucher — which led to a final diagnosis.
The patient’s tests of heart function were normal when she was 6 months old, but at 16 months old, she showed malfunction of the cardiac muscle and thickening of the ventricular walls. The girl started taking heart medication and enzyme replacement therapy (ERT) to restore cardiac function.
When the patient was 2 years, 7 months old, she could walk without support and speak whole sentences. Her spleen size, liver tests, and heart function were normal, and her blood parameters were almost normal. When she reached a year without showing signs of heart malfunction, she stopped taking heart medication but continued on ERT.
The second patient was the 11-year-old sister of the first patient. She had normal neuromotor development but performed poorly at school and was short for her age. She also had recurrent nosebleeds, an enlarged liver and spleen, and a deficiency of red and white blood cells and platelets.
The patient underwent bone marrow transplantation, and doctors found Gaucher cells — cells with abnormal lipid storage — in her bone marrow. She also had reduced β-Glucosidase activity and presented the same mutation as her sister, which led to type 3c Gaucher diagnosis.
The doctors found that the patient had reduced function of the cardiac muscle and calcium deposits in the aortic valve — the valve that connects the heart to the aorta — which caused severe cardiovascular disease. The patient received ERT for two months but died at age 12 of sudden cardiac arrest.
“Our cases were important because they had different clinical findings. Severe liver disease may be related to a second unknown disease which is combined with [Gaucher disease] type 3c in Patient 1. Patient 2 illustrated that late diagnosis causes high mortality and morbidity,” researchers stated.
“[These cases] highlight the importance of variable clinical findings in GD. Early diagnosis and early treatment are important for avoiding mortality and morbidity,” they concluded.
