A new mutation, H413P, that may be associated with severe symptoms was discovered in a Chinese baby with perinatal lethal Gaucher disease, a case report suggests.
The report, “A Neonatal Case With Perinatal Lethal Gaucher Disease Associated With Missense G234E and H413P Heterozygous Mutations,” appeared in the journal Frontiers in Pediatrics.
Perinatal lethal Gaucher disease (PLGD) is the most aggressive type of Gaucher disease, manifesting before birth or during early infancy. In the report, researchers in China described the case of an infant who developed PLGD that was caused by two independent mutations in the glucocerebrosidase (GBA) gene.
The mother, a 33-year-old woman, showed signs of miscarriage five weeks into the pregnancy and had to take progesterone until week 13. At week 24, she developed edema — fluid accumulation — in her limbs, which gradually worsened. She was diagnosed with gestational diabetes at week 25.
At week 36 of gestation, reduced amounts of amniotic fluid and abnormally small lungs were observed in the fetus, which led doctors to induce delivery. The patient was born with unusually rapid breathing and was admitted to the neonatal intensive care unit (NICU).
An initial examination revealed weak crying, difficulty breathing, fluid accumulation in the limbs and face, dry, delicate skin, and an enlarged liver and spleen.
The infant only moved when stimulated and had brief jerking spasms. His genitalia was not wholly formed. Examination of the placenta and umbilical cord suggested chronic inflammation.
During his time in the NICU, the patient was on respiratory support and fed through a gastric tube.
Lab tests showed reduced platelets and red blood cells, elevated liver enzymes — a sign of liver damage — and low levels of proteins in the blood.
The patient received treatment to increase the levels of platelets and red blood cells with no results. When the boy was 5 days old, the doctors performed a bone marrow puncture but found no Gaucher cells — cells that accumulate lipids and are characteristic of Gaucher disease.
Imaging exams showed that the lungs were not getting enough air and that the brain had small bleeding lesions. The damage to his brain and lungs worsened with time. At 14 days of age, the baby started having frequent seizures.
The combination of symptoms suggested a metabolic disease. When the patient was 44 days old, the doctors measured the activity of β-glucocerebrosidase and found it was zero, which led to a diagnosis of PLGD.
A genetic analysis showed two independent mutations in the GBA gene. The mutation G234E had been previously reported, but is not associated with severe Gaucher disease. The mother of the patient had the same mutation, but normal levels of β-glucocerebrosidase.
The second mutation, H413P, had not been reported in Gaucher patients. The investigators noticed that “the H413P mutation … possibly alters the structural properties at the active site and hence fundamentally eliminates the enzymatic function,” being the likely culprit for the early deaths of PLGD patients.
“It may be a serious and harmful mutation,” they said.
After his diagnosis, the baby’s parents decided to stop treatment and requested that they bring him home, so he was discharged. The baby continued to receive feeding through a gastric tube and oxygen through a mask, but his symptoms continued to worsen. He died after 73 days due to lung, liver, and kidney failure.