A Syndrome Associating Partial Albinism and lmmunodeficiency





M.D., Ph.D.



Paris, France

From the Groupe de Recherches d’lmmunologie et de Rhumatologie Pbdlatriques (I.N.S.E.R.M. U 132). H6pital des Enfants Malades, 75015 Paris, France. Requests for reprints should be addressed to Dr. Claude Grlscelll, Unite d’lmmuno-llbmatologic. Hbpltal des Enfants Malades, 149 Rue de SBvres, 75730 PARIS CEDEX 15 (France). Manuscrlpt accepted March 13, 1978.

Two unrelated patients with partial aibinism, frequent pyogenic infections and acute episodes of fever, neutropenia and thrombocy topenia are described. Their pigmentary dilution was characterized by large clumps of pigments in the hair shafts and an accumulation of meianosomes in meianocytes. Meianocytes had few short dendritic expansions, and keratinocytes were hypopigmented. No or few Langerhans’ ceils were detected in skin by electron microscopy and ATP-ase reactions. This pigmentary dilution, different from ail other human aibinisms, resembles the unique defect of the mutant dilute (d-d) mouse. Despite the presence of an adequate number of T and B lymphocytes, the patients were hypogammagk&uiinemic, deficient in antibody production and incapable of manifesting delayed skin hypersensitivity or of rejecting skin grafts. Their ieukocytes did not stimulate normal lymphocytes and could not generate cytotoxic ceils during mixed leukocyte reaction. T lymphocytes of one patient were unable to exert a helper effect on the maturation of B lymphocytes into immunogiobuiin-contatning ceils following in vitro stimulation with pokeweed mitogen. This suggests that the humorai deficiency might be secondary to a defect of helper T lymphocytes. Granuiocytes did no! show any morpho~ic abnormaitty, and their bactericidal activity was only moderately reduced. An increased number of poiymorphonuciear leukocytes with polar distribution of Concanavaiine A (Con A) receptors (capping) was found in one patient and her parents. The family histories suggest that this syndrome is transmitted as an autosomai recessive character. Among the partial albinisms, only the Chediak-Higashi (CH) syndrome has been associated with impaired host defense mechanisms [ l-31. The susceptibility to infections of patients with the CH syndrome is generally attributed to a defect of granulocytes since their cellular and humoral immune functions are intact [4]. Granulocyte abnormalities were first evidenced by the presence of giant granules, and defective metabolic and bactericidal functions [5-81. More recently, an abnormal distribution of Concanavaline (Con A) receptors on the surface of polymorphonuclear leukocytes was found [9]. We describe two patients with a pigmentary dilution characterized by a new form of limited transfer of melanin from melanocytes to keratinocytes, and a primitive defect of T lymphocytes resulting in secondary B cell dysfunction. Studies of their granulocytes revealed some metabolic dysfunction and an increased cap formation of Con A receptors on polymorphonuclear leukocytes but an absence of giant granules.

October 1979

The American Journal of Medlclne

Volume 65




Serum lmmunoglobulin Levels In Patients 1 and 2 and Three Patients with the Chediak-Higashi Syndrome (CH 1, CH 2, CH 3)

Age Patient


Patient CH 1 CH2 CH 3


NOTE: Levels


(mg1100 ml)

(mg/lOO ml)

(mg/lOO ml)

(mg1100 ml)


W (Wml)

6 7 9 11 12 13 0.5 4 5 5

525 360 410 262 150 327 250 1,300 2,200 1,200

81 64 42 16 8 21 18 190 166 102

35 47 352 20 9 900 76 120 84 102

0 0 0 0 0 10 2 11 4.5 1.2

23 20 20 20 10 10 0 42 100 120

of IgM, IgG, IgA and IgD were tested

by radial-immunodiffusion

CASE REPORTS Patient 1. This 11 year old North African girl was born on August 30, 1965; her parents were first cousins. Her birth weight was 3,600 g and her hair looked silvery grey. At two months of age, she had diarrhea. Five months later, she was hospitalized for pneumonia and peritonitis. She had received BCG at birth, without BCG dissemination. For the following six years she suffered repeated episodes of bronchopneumonia, tonsillitis, adenitis and dacrocystitis for which she required prolonged antibiotic treatment. At age seven, because of a lung infection, she was transferred to our hospital with a presumed diagnosis of the CH syndrome. On admission, the patient was feverish and poorly developed. Her weight was 14 kg and her height 99 cm. Her hair, eyebrows and eyelashes were silvery grey. Although presenting some areas of depigmentation, her skin was mildly hyperpigmented. She did not exhibit photophobia nystagmus or skin photosensitivity. There was no detectable reduction in ocular pigmentation or disturbance in the red reflex. She had generalized lymphadenopathy, large tonsils, crepitant rales and ronchi over both lung fields, and clubbing of the fingers. Liver and spleen were palpable 3 to 4 cm below the costal margin. Neurologic and mental examinations were within normal limits. Hemogram showed a hemoglobin level of 13 g/100 ml, a platelet count of 165,000/mm3, a white blood cell count of 7,000/mm3 with 20 per cent lymphocytes, 70 per cent neutrophils and 1 per cent monocytes, and an erythrocyte sedimentation rate of 6. The pathognomonic granules of the CH syndrome were not observed in smears of the peripheral blood and of a normocellular marrow specimen. The karyotype was normal. Blood chemistry studies revealed no abnormalities, except for a low level of gamma globulin (Table I) and a pronounced hyposideremia (30 y/100 ml). Roentgenograms showed bilateral infiltrates of the lungs. Staphylococcus aureus was cultured from the sputum. Treatment with intravenous antibiotics resulted in complete diminution of the lung abnormalities and of the hepatosplenomegaly. Further studies of the skin and hair, as well as repeated blood and marrow smear examinations, did not reveal the characteristic features of the CH syndrome, casting doubt on the initial diagnosis.





October 1978

The American Journal of Medlclne

and IgE by a radioimmuno&say.

The patient has now been under our care for six years, during which the evolution of her disease was characterized by the following: (1) Repeated infectious episodes, the most severe being bronchopneumonia, lung abscess and pleurisy. At the age of eight, bronchiectasia of the lower segment of the left lobe imposed a lobectomy complicated by purulent pleurisy. The patient now suffers from respiratory insufficiency with right-sided heart failure. Skin abcesses, perilabial and periorbital cellulitis with dacrocystitis, pharyngosinusitis, otitis, cervical adenitis and diarrhea occurred frequently. Various cultures have grown Staph. aureus, Pneumococcus, Escherichta coli, Proteus, betahemolytic Streptococcus and Neisseria sicca. Candida albicans was also frequently isolated in stools and sputums. One blood culture grew alpha-hemolytlc Streptococcus. (2) Six episodes, not always related to infections, characterized by fever, increased hepatosplenomegaly and increased silvery depigmentation of the hair were observed. Thrombocytopenia (500 to 20,000/mm3) and granulocytopenia (0 to 500/mm3) occurred without anemia or lymphopenia. The marrow aspirate and biopsy specimen revealed a normal or increased number of megakaryocytes and a mild diminution of the granulocytes (20 to 35 per cent) with normal maturation. The erythroid series remained normal each time, and the percentage of lymphocytes was significantly increased (40 to 50 per cent). The fibrinogen level was decreased on some occasions together with coagulation factors II, VII and X. Fibrinogen split products were detected once. Antibodies to platelets, leukocytes or erythrocytes were never detected. The total complement hemolytic activity was normal. Increased serum immunoglobulin M (IgM) levels were transiently observed on several occasions during the “acute phase” of the disease (Table I). An improvement was obtained each time within three to five weeks after the administration of intravenous antibiotics, steroids and transfer factor (1 U subcutaneously/week), and/or levamisole (3 mg/kg, three days a week). However, transfer factor (1 U/month), levamisole or ascorbic acid (200 mglday) failed to prevent relapses. Since the last relapse, the patient has had a per-

Volume 65


sistent hepatosplenomegaly which contrasts with the hypoplasia of lymph nodes and tonsils. Patient 2. This girl, born on May 21, 1975, was the fifth child of nonrelated Caucasian parents. A sister and a brother with silvery hair died, respectively, at two and a half and one and a half years of age. The characteristic granules of the CH syndrome were not visualized in their leukocytes although at postmortem examination both showed a lymphohistiocytic infiltration of lymphoid organs. Because of the family history and depigmentation of her hair, this patient was seen elsewhere at five months of age, before she had had any clinical manifestations. Her hair looked silvery blonde, but the skin was of normal coloration with a single (1 cm*) depigmentation spot on the right side of the abdomen. There was no photophobia, nystagmus or ocular albinism. The liver, spleen and lymph nodes were enlarged. On admission, the hemoglobin level was 8.7 g, white blood cell count 5,800/mm3 with 5 per cent polymorphonuclear leukocytes, 87 per cent lymphocytes and 8 per cent monocytes, reticulocytes 1 10,000/mm3 and platelets 150,000/mm3. Cytologic examination of blood and bone marrow smears did not reveal the giant granules of the CH syndrome. One month later, an acute phase occurred with high fever, semicomatous state, increased volume of liver and spleen, jaundice, thrombocytopenia (

A syndrome associating partial albinism and immunodeficiency.

CASE REPORTS A Syndrome Associating Partial Albinism and lmmunodeficiency CLAUDE GRISCELLI, M.D. ANNE DURANDY, M.D. DELPHINE GUY-GRAND, FRITZ DAGU...
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