A 2-year-10-month old typically developing girl,　born out of second-degree consanguinity with no significant family history,　presented with abnormal movement of eyeballs and ataxia for 10 days.　Over the next 2 days, the child was not recognizing anyone and not speaking any meaningful words. She deteriorated further in another 2-3 days and was not aware of self and surrounding,　passing urine and stool in clothes, not eating food, and biting family members when held. She was restless and used to sleep only 2-3 hours in a day. There was a past history　of　gradually progressive blackish pigmentation of　skin　since the age of 8 months. In addition, there were recurrent hospital　admissions for respiratory tract infections requiring treatment for 5 to 10 days,　the last one　being three weeks ago.　

On examination, the child was restless, inattentive and was not recognizing family members. Her weight, length and head circumference were 9 Kg (-3.33 SD), 84 cm (-2.60 SD), 45 cm (-2.33 SD), respectively.　Pallor was present; there was no cyanosis, icterus, lymphadeno-pathy, petechiae or ecchymosis. Child　was having silvery hair, diffuse hyperpigmentation over face, trunk, extremities sparing flexural region with salt and pepper pigmentation over forearms and thighs (Fig. 1a). Neurological examination revealed minimally conscious state with evidence of pendular nystagmus,　generalized hypotonia, extensor plantar response bilaterally, and brisk deep tendon reflexes. Hepatosplenomegaly was also noted.

Fig. 1 (a) Slivery hairs with hyperpigmentation over face and upper limbs;　(b) Hair shaft showing　evenly distributed regular melanin granules larger than normal hairs;　(c) Bone marrow smear showing many large sized granules in the cytoplasm of cells of granulocytic series, erythroid cells and lymphocytes normal.

Differential diagnoses for neurological worsening in this child with silvery hair syndrome included autoimmune encephalitis, accelerated phase of hemophagocytic lymphohistiocytosis (HLH), central nervous system infections,　Opsoclonus-myoclonus-ataxia syndrome (OMAS)　or Landau-Kleffner syndrome.

Final　diagnosis of CHS with Anti-NMDAR autoimmune encephalitis was made;　however, we could not perform genetic testing for CHS due to financial constraints.　Child　was treated with intravenous methylprednisolone initially but there was no improvement, and she also developed multiple abnormal movements in the form of　choreoathetosis, orofacial dyskinesia and hemiballismus during the course,　 and thus intravenous immunoglobulin was added.　Child　also received levetiracetam, risperidone and antibiotics. She started showing improvement after two weeks of hospitalization and was discharged on oral steroids, antiepileptics along with trimethoprim-sulphame-thoxazole prophylaxis and vitamin C for CHS. Presently child is under follow up for 3 months. She is now able to walk independently, feeds herself, recognize family members, can speak in sentences, can undress; there are no seizures or abnormal body movements.

Silvery　hair is a rare clinical manifestation of syndromes presenting as silvery hair syndrome, consisting of CHS, Griscelli syndrome, and Elejalde disease. These can be differentiated by light microscopic examination of skin and hair shafts along with immunological and peripheral blood smear evaluation [1].　CHS is a rare disorder with an　estimated　incidence of <1 in 1,000,000. The underlying defect in CHS is abnormal organellar protein trafficking that leads to aberrant fusion of vesicles and failure to transport lysosomes to the appropriate site of action due to the mutation in the　CHS1/LYST　gene at 1q42 [2]. Clinical manifestations include　aberrant pigmentation and ocular manifestations, immuno-deficiency with predominantly bacterial infections, coagulation defects, progressive neurologic dysfunction and HLH [1]. Neurological manifestations　include subtle and non-specific neurodevelopmental issues,　insidious onset gradually progressive motor and sensory　peripheral neuropathy, ataxia, tremors, cranial nerve palsies, intellectual decline, and seizures.　 Others include spinocerebellar degeneration, Parkinson disease-like movement disorders and dementia especially in the second and third decade of life. Neuroimaging shows diffuse atrophy of brain and seizure activity may be there on EEG [3,4].

Differential diagnoses of childhood encephalitis are vast, and autoimmune encephalitis has become a well-recognized entity over past two decades. Most common presenting features include seizures, behavioral changes, confusion, neuropsychiatric symptoms and movement disorders　chorea, athetosis,　myorhythmia or dystonia [5,6].

Our major differential diagnosis in present case was HLH, but absence of fever, normal levels of serum ferritin and triglycerides in the clinical context of acute encephalopathy with hepatosplenomegaly pointed against this diagnosis. Hepatosplenomegaly and neutropenia has been described in asymptomatic cases of CHS [1,7]. However, we were not able to carry out the molecular test or NK cell activity. Considering age of presentation, ataxia, restlessness and behavioral issues being predominant symptoms, another closest differential was OMAS. In OMAS, chaotic multidirectional eye movement called opsoclonus are classically described but our patient had horizontal nystagmus and the type of abnormal body movements which she developed gradually are also not frequently described with OMAS [8].　Subacute course of illness, predominant neuro-psychiatric issues and movement disorders were more in favour of AIE.

Recent literature suggests that　immuno-deficiency and　autoimmunity　are two sides of the same coin. Common variable immunodeficiency and selective IgA deficiency are often associated with autoimmune phenomena and case reports of AIE with these disorders are described in the literature [9,10]. However, autoimmune encephalitis with a disorder of phagocytic dysfunction has not been reported earlier.

Contributors: All authors contributed to management of the patient, drafting of manuscript, approved the final version of manuscript and agree to be accountable for authenticity and integrity of the work.

Funding: None; Competing interest: None stated.

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