متلازمة شيدياك هيغاشي

Chediak-Higashi syndrome is inherited as an autosomal recessive disease. It was described over 50 years ago. Clinical reports have identified mutations throughout the CHS1/LYST lysosomal trafficking gene.¹ The nature of the mutation can be a predictor of the severity of the disease.² There are a number of animal models including mouse, cat, cattle, mink and killer whale.¹

علم الأوبئة

The disease is exceptionally rare with fewer than 500 cases reported in the literature.³

عرض^{3 4}

Chediak-Higashi syndrome is characterised by partial oculocutaneous albinism, immunodeficiency, and a mild bleeding tendency.

In 85% of cases, Chediak-Higashi Syndrome develops into an accelerated phase characterised by pancytopenia, high fever, and lymphohistiocytic infiltration of the liver, spleen, and lymph nodes.⁵

Clinical features of Chediak-Higashi syndrome include:

• Impaired vision, photophobia.

• Albinism of the OCA2 type, giving a lighter complexion than unaffected family members.⁶

• Silvery sheen to hair which may be fair in colour.

• Frequent infections (skin, mucous membranes, respiratory).

• الصرع.

• Mental retardation.

• Enlarged liver and spleen, jaundice.

• Ataxia causing incoordination and a typical ataxic gait; tremor.

التشخيص التفريقي

Initially the condition may present as one of the varieties of albinism but the recurrent infections should make one suspect the diagnosis. The Hermansky-Pudlak syndrome and Griscelli's syndrome are similar but distinct conditions.³

التحقيقات⁴

The diagnosis is established in a proband with giant inclusions within leukocytes on peripheral blood smear and/or by the identification of biallelic pathogenic variants in LYST on molecular genetic testing.

• Blood smear shows giant granules in the neutrophils that stain for peroxidases.

• Bone marrow smears show giant inclusion bodies in leukocyte precursor cells.

• Giant granules are also found in cells from biopsy of skin, muscle and nervous system.

• Platelet or leukocyte levels are abnormally low.

• Genetic testing may show mutations in the CHS1 gene.

• Light or polarised light examination of hair shafts can help to diagnose Chediak-Higashi syndrome but cannot differentiate it from the appearance seen in Griscelli's syndrome.⁷

• Fluorescence cytometric analysis of cellular granularity and surface molecules offer useful diagnostic information.

• EEG may be abnormal.

• Brain MRI or CT scan may show small brain due to atrophy.

• Oral radiographs may reveal extensive loss of alveolar bone, often resulting in tooth exfoliation. .

• EMG or nerve conduction velocity testing may show delayed nerve conduction.

• A red light reflex is present in the eye (this is frequently seen in albinism).

• There are abnormalities of immune function including reduced level of CD4 lymphocytes.

الأمراض المرتبطة

• Infection is a constant problem.

• For a better understanding of the visual defects and the problems related to the OCA2, see the separate record on المهق.

الإدارة⁴

• Initial chemoimmunotherapy followed by transition to continuation therapy for the accelerated phase.

• Allogenic stem cell transplant as soon as possible to cure haematological and immunological defects.

• L-dopa may be considered for those with parkinsonism.

• Home modifications and intensive rehabilitation for those with ataxia and other neurological complications.

• Corrective lenses to improve visual acuity, sunglasses to protect sensitive eyes from UV light.

• Sunscreen to prevent sun damage and skin cancer.

• Management of other presenting features, eg, epilepsy.

الاستشارة الوراثية

Chediak-Higashi Syndrome is inherited in an autosomal recessive manner. When both parents are heterozygous, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

Prenatal testing of CHS is possible if the pathogenic variants have been identified in the family.

المضاعفات⁴

Frequent infections lead to hypersplenism which in turn causes thrombocytopenia and haemorrhage.

About 85% of patients develop an unusual ليمفوما. This is called the accelerated phase and is characterised by generalised lymphohistiocytic infiltrates, fever, jaundice, hepato-splenomegaly, lymphadenopathy, pancytopenia and bleeding.¹

التكهن

Without stem cell transplant, death before the age of 10 is common.¹

The prognosis for the accelerated phase is poor and the only treatment is allogenic haematopoietic stem cell transplantation (HSCT).⁸

All affected individuals including adolescents and adults with atypical Chediak-Higashi syndrome and children with classic Chediak-Higashi syndrome who have successfully undergone allogenic haematopoietic stem cell transplantation develop neurological findings during early adulthood (peripheral neuropathy causing motor and sensory changes and weakness).⁴