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Isolated Sixth Nerve Palsies in a Child With Familial Hemophagocytic Lymphohistiocytosis Type 2
Homer H Chiang1, Sebastian Fernandez-Pol, Gordon H Bae
1Department of Ophthalmology (HHC), Stanford University School of Medicine, Palo Alto, California; and Departments of Pathology (SF-P), Dermatology (GHB), Pathology and Dermatology (KER), Radiology (HMD), and Ophthalmology, Neurology and Neurosciences (SJB), Stanford University School of Medicine, Stanford, California.
Insights
Familial hemophagocytic lymphohistiocytosis (HLH) Type 2, a rare genetic disorder, can mimic demyelinating diseases in children. Prompt genetic testing is crucial for accurate diagnosis and timely treatment, leading to recovery.
Area of Science:
- Pediatric Neurology
- Immunology
- Genetics
Background:
- Demyelinating diseases and familial hemophagocytic lymphohistiocytosis (HLH) can present with overlapping neurological symptoms in children.
- Early diagnosis of HLH is critical for effective treatment and improved outcomes.
Observation:
- A 2-year-old boy presented with cranial nerve palsies and brain MRI abnormalities suggestive of demyelinating disease.
- Corticosteroid treatment was ineffective, and his condition worsened with new neurological deficits.
- His infant sister presented with fever, pancytopenia, and hemophagocytosis, prompting genetic investigation.
Findings:
- Genetic testing revealed biallelic mutations in the PRF1 gene in both siblings.
- The final diagnosis was familial HLH Type 2.
- The boy's neurological symptoms and MRI findings resolved after chemotherapy and bone marrow transplant.
Implications:
- This case highlights the importance of considering HLH in pediatric patients with neurological symptoms that do not respond to typical treatments for demyelinating conditions.
- Early genetic testing for HLH is essential for accurate diagnosis and management.
- Successful treatment with chemotherapy and bone marrow transplantation offers a favorable prognosis for familial HLH Type 2.
Abstract:
A previously healthy 2-year-old boy presented with a left sixth cranial nerve palsy. There was a family history of multiple sclerosis and optic neuritis. Neuroimaging showed multiple foci of T2/FLAIR hyperintense signal abnormality in both cerebral hemispheres and in the brainstem. The initial diagnosis was suspicious for demyelinating disease. However, there was no clinical improvement after a course of corticosteroids, and there was no change in his follow-up MRI. He later developed bilateral sixth nerve palsies, with esotropia addressed with bilateral medial rectus botulinum toxin injections. A brain biopsy was planned. However, his 3-month-old sister was separately admitted for fever and pancytopenia. She had markedly elevated ferritin, D-dimer, triglycerides, sIL-2R, CXCL9, and IL-18 and low fibrinogen. Her bone marrow biopsy showed hemophagocytosis. Genetic testing of both siblings revealed biallelic mutations in the PRF1 locus. The final diagnosis of familial hemophagocytic lymphohistiocytosis Type 2 was made. Both siblings underwent chemotherapy. The boy's sixth nerve palsies and MRI abnormalities resolved. Both siblings then went on to undergo bone marrow transplant.
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