Chediak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder of the immune system characterized by chronic infections, neutropenia, partial oculocutaneous albinism, and bleeding diathesis with partial neuropathy. The disease usually appears during infancy or childhood, and proves fatal in many of the patients in the first decade of their life. Progress to the accelerated phase of the disease is usually precipitated by a viral infection. When expressed first in adults, the disease usually takes a much milder course. Typical symptoms include nystagmus, decreased vision, and photophobia, albinism, a silvery sheen to the hair, increased cutaneous, oral and respiratory infections, ataxia, and peripheral neuropathy.
Diagnosis is made on the basis of clinical symptoms, and additional tests. Giant, peroxidase-positive granules can be seen in the WBCs, as well as in the skin, muscle, and nervous cell biopsies. WBCs show an abnormally low level, and the spleen and liver may be enlarged. Other findings include seizures on EEG, small, atrophied brain on MRI, and delayed nerve conduction on EMG. Treatment mostly involves administration of antibiotics or antiviral therapy to cure the infection. No specific cure for the underlying pathology is available. However, bone marrow transplants have been successful in some patients.
CHS arises from mutations in the Lysosomal Trafficking Regulator (LYST) gene on chromosome 1. LYST is involved in the sorting of endosomal resident proteins into late multivesicular endosomes by a mechanism involving microtubules.
[See: Syria > Shome et al., 2002]
Al-Sheyyab et al. (2000) reported the presence of Chediak-Higashi syndrome in eight cases from three families in Jordan. No further details could be obtained at the time of editing this record.
Kandil (1996) reported for the first time a Bedouin male patient (aged 11 years) with Chediak-Higashi syndrome. He presented with partial oculo-cutaneous albinism and recurrent pyogenic infections. Clinical examination of skin and hair shafts revealed irregular melanin clumps, while hematological investigations showed pathognomonic intracytoplasmic giant granules. Partial improvement was achieved through administering high doses of Vitamin C. [Kandil HH. Chediak-Higashi syndrome in Bedouin sibs. Kuwait Med J. 1996; 28(1):44-8.]
Karim et al. (1997) studied the case of a Bedouin Kuwaiti patient born to first-cousin and had homozygosity for the 1-bp insertion mutation (adenine) at codons lys633/lys634 in the LYST gene. The boy had a typical severe childhood CHS with silvery hair and oculocutaneous albinism, recurrent pyogenic infections, cervical lymphadenopathy, hepatosplenomegaly, neutropenia, mild thrombocytopenia, and low serum IgG. Typical cytoplasmic giant granules were seen in peripheral blood leukocytes, and a skin biopsy showed large irregular melanin granules in the melanocytes.
Harfi and Malik (1992) reported the case of a 10-year-old boy with Chediak-Higashi syndrome in accelerated phase who failed to respond to treatment with ascorbic acid, vincristine, and prednisone. Splenectomy resulted in clinical, hematologic, and immunologic improvement: his leukocyte chemotactic and phagocytic functions returned to normal.
Al-Nasser et al., (1993) reported five Saudi boys, ages 18 months to ten years, diagnosed with Chediak-Higashi syndrome between June 1978 and December 1990. All were born to first degree consanguineous parents. All patients presented with typical clinical and laboratory characteristics of the Chediak-Higashi syndromeFour out of five patients showed hyperpigmentation in the irides and various skin areas. Three of the patients were in the accelerated phase; two of them responded to combination chemotherapy and one improved after splenectomy. In addition, all patients suffered from cerebral atrophy. All patients died in the first decade of their lives.
In 2003, Al-Khenaizan described a 4 1/2 -year-old Saudi Arabian boy born to consanguineous parents who was initially seen with gradual onset of fever and abdominal distention. The patient was found to have speckled hypopigmentation and hyperpigmentation of the sun-exposed areas. The finding of large cytoplasmic granules in blood and bone marrow leukocytes established the diagnosis of Chediak-Higashi syndrome.
Shome et al. (2002) described the case of a 2-month-old Syrian infant, born to consanguineous parents. The baby presented with fever, and poor feeding. She appeared pale, and had light-colored hair with a silvery sheen, photophobia, and severe oral candidisis. The patient was found to have moderate splenomegaly, as well as lymphocytosis with neutropenia. Eye examination showed bilateral transilluminant iris, orange-red reflex, and retinal hypopigmentation. Although all bacteriological cultures were negative, she was also found to be positive for CMV and EBV IgG antibodies. Shome and colleagues suggested that this could be because of a congenital viral infection. Blood count showed a hematocrit level of 28%, and 90% lymphocytes, with 21% atypical lymphocytes. The peripheral blood lymphocytes also showed cytoplasmic inclusions, which were myeloperoxidase-positive, suggesting CHS. Interestingly, although both her parents were normal, her father's blood smear also showed large cytoplasmic granules in some lymphocytes. Bone marrow aspiration studies also confirmed the abnormal presence of lymphomononuclears and macrophages in the patient, suggesting the accelerated phase of CHS. The patient showed little improvement when treated with antibiotics, packed red cells, and platelet. Her condition improved only after the administration of granulocyte colony stimulating factor (G-CSF). After a week, however, even the G-CSF failed to bring any improvement, and she was put on combination chemotherapy of vincristine, cycophosphamide, and prednisolone. Although this treatment brought temporary clinical remission, neutropenia was not abrogated. A week after discharge, the patient was found to have urinary tract infection, and gastroenteritis. Simultaneously, she developed bleeding diathesis with epistaxis, and died at the age of 5-months.
[Shome DK, Al-Mukharraq H, Mahdi N, Ameen G, Farid E. Clinicopathological aspects of Chediak-Higashi syndrome in the accelerated phase. Saudi Med J. 2002; 23(4):464-6.]