Patients with Gaucher disease type 1 (GD1) may exhibit neurological symptoms at a young age, requiring the use of genetic testing for diagnosing the specific disease type and developing a treatment plan, researchers advise in a recent study.
The study, “Are There Neurological Symptoms in Type 1 of Gaucher Disease?” appeared in the Iranian Journal of Child Neurology.
GD1 is the most common form of the disease, and includes symptoms such as bone pain and fractures, an enlarged liver and spleen, and reduced blood cell levels. Patients often have fatigue and chronic infections, and they generally bruise easily.
Although GD1 is the disorder’s non-neuropathic form, which means the central nervous system is usually not affected, prior research in adult patients reported neurological issues such as dementia, parkinsonism, and psychomotor delay. Accordingly, debate is ongoing over current GD classification and whether the disorder is a continuum between neuropathic and non-neuropathic forms.
In Gaucher type 3 (GD3), which typically manifests later in life than Gaucher type 2 (GD2), the most frequent symptoms are bone abnormalities, eye movement, respiratory and blood problems. Brain-related symptoms are progressive, and include seizures, cognitive impairment, and lack of coordination.
The scientists compared neurological symptoms in patients with GD1 or GD3. In their study, patients with symptoms suggestive of GD were followed over 10 years in a hospital in Tehran, Iran. Overall, patients showed blood disorders, skeletal system and respiratory problems, and enlarged organs. Neurological involvement included seizures, cognitive deficit, ataxia, and developmental disability.
The activity of beta-glucocerebrosidase, the enzyme affected in GD, was tested in patients’ white blood cells and fibroblasts. Genetic testing was then performed to confirm diagnosis. Physical exams, as well as assessments of cognitive and developmental status, behavioral disorders and seizures, were also conducted.
A total of eight patients with GD1 and three with GD3 were included, seven of whom were female. Mean patient age was approximately 10 years, ranging from 5-30 years old.
All patients had reduced beta-glucocerebrosidase activity. Additionally, they were all from consanguineous marriages, which means the parents were related to each other, while three had a family history of similar diseases.
Major complaints of GD1 patients at the time of presentation were abdominal distention and discomfort (75%), nosebleed (25%), and anorexia and weight loss (25%). Only one patient had difficulty walking. Patients with GD3 had similar symptoms as those with GD1. All showed a delay in teeth growth.
Neurological deficits were observed in all eight GD1 patients, including cognitive impairment in one patient, developmental delay and microcephaly (smaller head circumference than normal) in four, and behavioral disorder, mild muscle stiffness, and increased deep tendon reflexes in three patients.
In patients with GD3, neurological findings included abnormal eye movements, developmental delay and cerebellar dysfunction in all three cases, as well as myoclonic seizures, behavioral disorder, and unsteady gait in one patient.
Compared with prior studies on GD1, the scientists commented that the difference in the observed neurological manifestations is due to the younger age of their patient group. Also, unlike previous research, these patients did not exhibit complications that may be secondary to systemic features of GD, such as bleeding disorders or abnormal gait.
“Unlike previous studies that mentioned GD type 3 and type 1 differentiated by existence of neurological involvements in type 3, we found that type 1 could also be presented with some neurological deficits,” the researchers wrote.
“Therefore, the neurological symptoms are not the important criteria for differentiation between different types of [GD], and genetic testing is required for confirmation of diagnosis and determining a treatment plan,” they said.
Further studies with larger patient groups are needed to confirm these neurological manifestations in different GD types, the investigators said.