Griscelli Syndrome Workup

Updated: Jul 26, 2019
  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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Laboratory Studies

Characteristic laboratory features include pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and hypoproteinemia. In Griscelli syndrome without delayed-type cutaneous hypersensitivity and impaired natural killer cell function manifests as the ever-present immunologic abnormalities.

Some patients with Griscelli syndrome have secondary hypogammaglobulinemia, impaired major histocompatibility complex–mediated cytotoxic effects, a decreased capacity of lymphocytes to trigger a mixed lymphocyte reaction, or various functional granulocytic abnormalities. One report noted low levels of immunoglobulin G2 in a patient with Griscelli syndrome.

Evidence of hepatitis can be demonstrated by abnormal liver function results. Neonatal hyperbilirubinemia (peak total bilirubin 26.5 mg/dL at age 4 wk) has been reported.

Chromosome analysis can be performed to detect mutations in MYO5A and RAB27A.

A prospective survey of degranulation assays for the rapid diagnosis of Griscelli syndrome and other familial hemophagocytic syndromes shows that such testing has promise. [43]


Imaging Studies

Both CT and MRI are used to assess Griscelli syndrome. Usually, findings are normal at birth. When the disease manifests, imaging findings are abnormal. Findings in the 2 variants (ie, MYO5A,RAB27A) of Griscelli syndrome are different.

Isolated congenital cerebellar atrophy was observed in a patient with the MYO5A defect. No evidence of infiltration of lymphocytes is present in these patients. In Griscelli syndrome caused by RAB27A defects, CT scan can show areas of coarse calcification in the globi pallidi, left parietal white matter, and periventricular and left brachium pontis.

Patients with Griscelli syndrome can manifest hypodense signals in the genu and posterior limb of the internal capsule on the right side (which is compatible with inflammatory changes), as well as posterior aspects of both thalami, together with minimal generalized atrophy. CT scanning can also suggest cell infiltration of the brain. In both variants, MRI can reveal areas of increased T2 signal intensity and a focal area of abnormal enhancement in the subcortical white matter. At birth, findings from long-bone plain radiography have been reported to be normal.

When Griscelli syndrome manifests, abdominal ultrasonograms can show hepatosplenomegaly with intrahepatic cholestasis and absence of bile duct distension.


Other Tests

Transmission electron microscopy of the skin shows an accumulation of numerous normal-sized stage IV mature melanosomes in the cytoplasm of melanocytes, with virtual absence of such melanosomes in adjacent keratinocytes. These findings allow Griscelli syndrome to be distinguished from Chediak-Higashi syndrome.

The peripheral blood smear shows no giant cytoplasmic granules in leukocytes. These findings allow Griscelli syndrome to be distinguished from Chediak-Higashi syndrome.

Neurologic evaluations reveal cerebral lymphohistiocytic infiltration and erythrophagocytosis with nonspecific electroencephalographic patterns. [44]

Valente et al [45] and Smith et al [46] noted that polarized light microscopy of hair shafts aids in the differential diagnosis of Chediak-Higashi syndrome and Griscelli syndrome.



Biopsy specimens of internal organs can reveal abnormalities. Liver biopsy specimens can show marked portal inflammation with focal hepatocellular necrosis.

Bone marrow aspiration samples can reveal slight hypocellularity with mild erythroid hyperplasia and hemophagocytosis.


Histologic Findings

The common histopathologic findings of Griscelli syndrome include prominent, mature melanosomes in skin and hair follicle melanocytes.

Griscelli syndrome demonstrates hyperpigmented basal melanocytes and sparse pigmentation of adjacent keratinocytes. This pathology of melanocytes and keratinocytes leads to large, clumped melanosomes in hair shafts, and, as a result, the hair has a silvery-gray sheen. These results can be highlighted in Fontana-Masson–stained sections. Light microscopy shows irregular, large aggregations of melanin pigment in hair.

Celik et al [47] investigated the light and scanning electron microscopic examination of hair in persons with Griscelli syndrome and found that the hair showed a normal cuticular pattern but nodular structures were present as abnormal findings.

Electron microscopic examination of the skin shows many mature melanosomes in melanocytes accompanied by few melanosomes in adjoining keratinocytes. Peripheral leukocytes lack giant granules. [30]