Objective: Our aim is to present a woman carrying a heterozygous GBA1 mutation who developed exclusively neurological symptoms in adulthood.

Background: The diagnosis of Gaucher disease (GD) relies on the findings of deficient glucocerebrosidase enzyme activity, or by the identification of biallelic pathogenic variants in GBA1 on genetic testing. GD is classified according to the presence/absence of neurological symptoms into: (i)Type 1-non-neuropathic, (ii)Type 2-acute infantile neuropathic and (iii) Type 3- chronic neuropathic. GD should be suspected in individuals with combination of CNS, skeletal, hematologic and other clinical findings. Individuals with GD and GBA1 heterozygotes have greater risk for Parkinson’s disease than non-carriers. It was reported that the current nomenclature for types 3 does not meet all clinical symptoms.

Method: A 31-year-old woman, whose mother is homozygous for GD, presented with progressive ataxia, tremor, poor coordination, left-sided hemiparesis, generalizied fasciculation, cramps and noice-startle. β-glucocerebrosidase activity on leukocytes was determined by enzyme assay. Genetic testing GBA1 was performed to confirm diagnosis.

Results: β-glucocerebrosidase activity was normal. Genetic testing revealed a heterozygous mutation carrier (c.1226A:G). Brain MRI, EEG, EMNG, abdominal ultrasound and laboratory findings were normal.

Conclusion: The present case is of relevant interest due to its atypical clinical presentation in adulthood in heterozygous GBA1 allele female carrier. Given that different heterozygous variations of GD described in the literature, it could be possible that described phenotype can be associated with complex heterozygous GBA1 variants. This warns us about the complexity of symptoms and disease course associated with GBA1 mutation.

References: 1. McNeill A, Duran R, Hughes DA, Mehta A, Schapira AH (August 2012). “A clinical and family history study of Parkinson’s disease in heterozygous glucocerebrosidase mutation carriers”. Journal of Neurology, Neurosurgery, and Psychiatry. 83 (8): 853–4.
2. Grabowski GA (October 2008). “Phenotype, diagnosis, and treatment of Gaucher’s disease”. Lancet. 372 (9645): 1263–71.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ataxia-tremor-fasciculations-and-hemiparesis-in-a-gba1-heterozygous-female-carrier/