A Case Report of Chediak-Higashi Syndrome Complicated with Systemic Amyloidosis and Olivo-Cerebellar Degeneration

Atypical Chédiak-Higashi syndrome with attenuated phenotype: three adult siblings homozygous for a novel LYST deletion and with neurodegenerative disease

“…Systemic AA amyloidosis has been reported previously in the setting of CHS, both in humans [20] and in animals [18]. The only previous human report described a Japanese woman with classic CHS who suffered recurrent pyogenic infections and albinism noted from infancy, and had post-mortem evidence of amyloid deposition in multiple tissues including the kidney, liver, thyroid, and ovary, and pituitary and parotid glands.…”

“…Consistent with our experience, other authors [8,19] have reported that granules in patients with attenuated disease are enlarged, but not as dramatically as is seen in classic forms of the disease; it is therefore conceivable that the diagnosis may be missed by inexperienced technologists. With regard to observed neurologic deterioration with advancing age, clumped irregular melanin granules have been observed in the substantia nigra in human patients at autopsy [20,21]. Murine models of CHS with homozygous missense mutations in LYST have exhibited predominant neurologic phenotypes including lower motor performance scores than controls, with accumulation of giant lysosomes in neuronal cells and intracytoplasmic inclusions in Purkinje cells of the cerebellum and motor cortex [22].…”

“…Murine models of CHS with homozygous missense mutations in LYST have exhibited predominant neurologic phenotypes including lower motor performance scores than controls, with accumulation of giant lysosomes in neuronal cells and intracytoplasmic inclusions in Purkinje cells of the cerebellum and motor cortex [22]. At autopsy, adults with CHS had neuronal degeneration involving the inferior olivary nuclei and the cerebellar cortex, with an overall distribution similar to late cortical cerebellar atrophy (LCCA) and olivopontocerebellar atrophy (OPCA), but without pontine involvement [20]. …”

“…Reactive gliosis was observed in the brain. The authors speculated that recurrent infections had contributed to the development of amyloidosis, and that amyloid deposition would become an increasingly common observation in CHS patients with classic phenotypes as a function of cumulative burden of recurrent, severe infection, especially as these patients survive into adolescence and adulthood in greater numbers as is anticipated as BMT protocols become more refined with improved efficacy and reduced toxicity [20]. Neutropenia, observed chronically or intermittently, has been reported in CHS [23], and the fact that our patients were not neutropenic at the time of evaluation does not exclude historical episodes of neutropenia.…”

Adult Chédiak-Higashi syndrome presenting as parkinsonism and dementia

“…Interestingly, this patient was first seen with a degenerative neurologic disorder in which, except for nystagmus, the major signs remained undeveloped until early adult life. In addition, this is the oldest known adult patient with C H S to be documented (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). In 15 adult cases of C H S including ours (1 1 males, 4 females), all had varying degrees of neurological signs (Table 2), especially loss of DTR due to peripheral neuropathy.…”