Early Diagnosis of an Infant with Gaucher's Disease Type 3. Case Report

Background

Gaucher's disease is a rare autosomal recessive disorder that results from the deficiency of the enzyme glucocerebrosidase, causing deposition of glucocerebroside in cells of the macrophage-monocyte system.

Type 3 disease has varied presentations, with neurologic involvement, in addition to progressive hepato-splenomegaly, anemia, thrombocytopenia and skeletal manifestations.

Case Report

2 month old infant girl, was noted to have abdominal enlargement, and was taken to the local rural provider. She was referred to a pediatrician. From there, she was transferred to our institution, after a red blood cell transfusion.

Past history is noteworthy for early passage of a first degree cousin, at the age of 3 months, with hepatosplenomegaly and transfusion requirements.

Parents deny consanguinity. However, they live in a very rural, closed population. A detailed pedigree chart was not obtained.

Physical exam revealed an infant in regular overall conditions, grade IV hepatosplenomegaly. Pale, fussy, hyporexic, with mild breathing difficulty, from enlarged abdomen. She had oculomotor apraxia, at the horizontal gaze. Rest of neurological examination was uneventful.

Dry blood sample was obtained and sent to a specialized laboratory (Greenwood Genetic Center, USA). Bone marrow biopsy showed almost total replacement of normal hematopoiesis, with Gaucher cells.

Beta glucosidase activity was low. GBA gene sequencing, at chromosome 1q21-22, revealed homozygous pL483p mutation, on exon 11. She was 5 months old, when diagnosis of Gaucher's disease type 3, was genetically confirmed.

Imiglucerase was initiated, biweekly, at 60 unit/kg. Dose was increased, on a monthly basis, up to 120 unit/kg. Ambroxol was also started, as a chaperone therapy 15mg/kg/d, as per recent literature (Narita et al, Ann Clin Transl Neurol 2016 Feb 2;3(3):200-15), providing increased glucocerebrosidase activity, in the cerebrospinal fluid, with improvement of neurologic symptoms.

Blood counts, including platelets, normalized shortly after starting enzyme replacement therapy. Neurologic milestones, growth and constitutional features, are adequate for age.

Hepatosplenomegaly has decreased with ongoing therapy, and we expect it will continue to ultimately improve, with treatment. She is now 14 months old.

Conclusion

Gaucher's disease is a rare condition that should be considered in an infant with hepato-splenomegaly and low blood counts, and or bleeding manifestations. Gold standard for diagnosis should be sought by the enzyme measurement, and molecular confirmation.

Enzyme replacement therapy is the therapy of choice, in these patients.

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