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Background Hemophagocytic lymphohistiocytosis is a life-threatening disease heralded by fever, cytopenia, hepatosplenomegaly, and multisystem organ failure. Its association with genetic mutations, infections, autoimmune disorders, and malignancies is widely reported. Case presentation A 3-year-old male Arab Saudi patient with insignificant past medical history and parental consanguinity presented with abdominal distension of moderate severity and persistent fever despite receiving antibiotics. This was accompanied by hepatosplenomegaly and silvery hair. The clinical and biochemical profiles were suggestive of Chédiak–Higashi syndrome with hemophagocytic lymphohistiocytosis. The patient received the hemophagocytic lymphohistiocytosis-2004 chemotherapy protocol and had multiple hospital admissions mainly due to infections and febrile neutropenia. After achieving the initial remission, the patient’s disease reactivated and did not respond to reinduction with the hemophagocytic lymphohistiocytosis-2004 protocol. Due to the disease reactivation and intolerance of conventional therapy, the patient commenced emapalumab. The patient was successfully salvaged and underwent an uneventful hematopoietic stem cell transplantation. Conclusions Novel agents such as emapalumab can be helpful for the management of refractory, recurrent, or progressive disease, while avoiding the toxicities of conventional therapy. Due to a paucity of available data on emapalumab, additional data are needed to establish its role in hemophagocytic lymphohistiocytosis treatment.

Background Autosomal-recessive hereditary spastic paraplegias (AR-HSP) consist of a genetically diverse group of neurodegenerative diseases characterised by pyramidal tracts dysfunction. The causative genes for many types of AR-HSP remain elusive. We tried to identify the gene mutation for AR-HSP with cerebellar ataxia and neuropathy. Methods This study included two patients in a Japanese family with their parents who are first cousins. Neurological examination and gene analysis were conducted in the two patients and two normal family members. We undertook genome-wide linkage analysis employing single nucleotide polymorphism arrays using the two patients’ DNAs and exome sequencing using one patient's sample. Results We detected a homozygous missense mutation (c.4189T>G, p.F1397V) in the lysosomal trafficking regulator (LYST) gene, which is described as the causative gene for Chédiak–Higashi syndrome (CHS). CHS is a rare autosomal-recessive syndrome characterised by hypopigmentation, severe immune deficiency, a bleeding tendency and progressive neurological dysfunction. This mutation was co-segregated with the disease in the family and was located at well-conserved amino acid. This LYST mutation was not found in 200 Japanese control DNAs. Microscopic observation of peripheral blood in the two patients disclosed large peroxidase-positive granules in both patients’ granulocytes, although they had no symptoms of immune deficiency or bleeding tendency. Conclusions We diagnosed these patients as having adult CHS presenting spastic paraplegia with cerebellar ataxia and neuropathy. The clinical spectrum of CHS is broader than previously recognised. Adult CHS must be considered in the differential diagnosis of AR-HSP.

Chédiak-Higashi syndrome (CHS) is a lethal disorder caused by mutations in the LYST gene that involves progressive neurologic dysfunction. Lyst -mutant mice exhibit neurologic phenotypes that are sensitive to genetic background. On the DBA/2J-, but not on the C57BL/6J-background, Lyst -mutant mice exhibit overt tremor phenotypes associated with loss of cerebellar Purkinje cells. Here, we tested whether assays for ataxia could measure this observed strain-dependency, and if so, establish parameters for empowering phenotype- and candidate-driven approaches to identify genetic modifier(s). A composite phenotypic scoring system distinguished phenotypes in Lyst -mutants and uncovered a previously unrecognized background difference between wild-type C57BL/6J and DBA/2J mice. Accelerating rotarod performance also distinguished phenotypes in Lyst -mutants, but at more advanced ages. These results establish that genetic background, Lyst genotype, and age significantly influence the severity of CHS-associated neurologic deficits. Purkinje cell quantifications likewise distinguished phenotypes of Lyst -mutant mice, as well as background differences between wild-type C57BL/6J and DBA/2J mice. To aid identification of potential genetic modifier genes causing these effects, we searched public datasets for cerebellar-expressed genes that are differentially expressed and/or contain potentially detrimental genetic variants. From these approaches, Nos1 , Prdx 2, Cbln3 , Gnb1 , Pttg1 were confirmed to be differentially expressed and leading candidates.

The blood smear showed giant lysosomes in the white blood cells (figure) and we diagnosed Chediak-Higashi syndrome, a rare autosomal recessive disease (gene CHS1/LYST at 1q42.1-2).

BackgroundThe classic form of Chédiak–Higashi syndrome (CHS), an autosomal recessive disorder of lysosomal trafficking with childhood onset caused by mutations in LYST, is typified ophthalmologically by ocular albinism with vision loss attributed to foveal hypoplasia or nystagmus. Optic nerve involvement and ophthalmological manifestations of the late-onset neurodegenerative form of CHS are rarely reported and poorly detailed.MethodsCase series detailing ophthalmological and neurological findings in three adult siblings with the late-onset form of CHS.ResultsAll three affected siblings lacked features of ocular albinism and demonstrated significant optic nerve involvement as evidenced by loss of colour and contrast vision, central visual field loss, optic nerve pallor, retinal nerve fibre layer thinning by optical coherence tomography (OCT) and abnormal visual evoked potential, with severity corresponding linearly to age of the sibling and severity of neurological disease. Further, unusual prominence of a ‘third line’ on macular OCT that may be due to abnormal melanosomes was seen in all three siblings and in their father. Neurological involvement included parkinsonism, cerebellar ataxia and spastic paraparesis.ConclusionsThis report expands the ophthalmological phenotype of the late-onset neurodegenerative form of CHS to include optic neuropathy with progressive vision loss, even in the absence of ocular albinism, and abnormal prominence of the interdigitation zone between cone outer segment tips and apical processes of retinal pigment epithelium cells on macular OCT.

BackgroundNeurological manifestations of Chediak-Higashi syndrome mainly include peripheral neuropathy, ataxia, tremors, cranial nerve palsies, intellectual decline and seizures.Case CharacteristicsA 2 years 10 month old girl with silvery hair syndrome presented with sub-acute onset behavioral issues, ataxia and multiple type abnormal movements. Cerebrospinal fluid examination was positive for Anti NMDA receptor antibodies. Hair shaft examination and peripheral blood film findings were suggestive of Chediak Higashi syndrome.MessageAnti NMDA receptor encephalitis may be associated with Chediak Higashi Syndrome.

Neurologic disorders in Chediak–Higashi syndrome are usually late presentations and also may manifest long after bone marrow stem cell transplantation. To the authors' knowledge, transient neurological deficit has not been reported yet. They describe a 6-year-old boy with Chediak–Higashi syndrome in the accelerated phase who presented with transient sixth nerve palsy. [J Pediatr Ophthalmol Strabismus. 2018;55:e22–e25].

A toddler presented with poor appetite, weight loss and frequent respiratory tract infections for the past 6 months, fever and increasing paleness for the past 2 months and bilateral pedal oedema for the past 1 month. Anthropometry confirmed severe acute malnutrition. Clinical and laboratory evaluation revealed that the child also had hypopigmented hair and skin, splenohepatomegaly, pancytopenia and hypoalbuminaemia. The coexistence of hypopigmentation and suspected low immunity prompted us to investigate the child's hair, peripheral blood smear and bone marrow. Hair under light microscopy showed evenly distributed, large melanin granules, suggestive of Chediak-Higashi syndrome (CHS). Peripheral blood smear and bone marrow aspirate examinations revealed abnormal large intracytoplasmic granules, which was diagnostic of CHS. The child's investigations revealed coexistent hemophagocytic lymphohistiocytosis, confirming the diagnosis of CHS in ‘accelerated phase’, which is fatal if not treated. The parents prematurely took the child home against medical advice, before definitive therapy could be instituted.

Patients with the Chediak-Higashi syndrome have an increased susceptibility to pyogenic infections. A double-blind study of the effect of cloxacillin or placebo on the incidence of bacterial infections was conducted on four of these patients. Twenty-two infections occurred, and it could not be shown that cloxacillin was significantly more effective than placebo in preventing infections. The study utilized a closed sequential scheme to evaluate the therapy; this statistical approach is of value in studies of small groups of patients.