OBSERVATION Elejalde Syndrome—A Melanolysosomal Neurocutaneous Syndrome Clinical and Morphological Findings in 7 Patients Carola Duran-McKinster, MD; Rodolfo Rodriguez-Jurado, MD; Cecilia Ridaura, MD; M. A. de la Luz Orozco-Covarrubias, MD; Lourdes Tamayo, MD; Ramon Ruiz-Maldonando, MD Background: Silvery hair and severe dysfunction of the and seizures. Mental retardation since the first months central nervous system (neuroectodermal melanolyso- of life was noted in 4 cases. Psychomotor development somal disease or Elejalde syndrome) characterize this rare was normal in 3 cases, but suddenly the patients pre- autosomal recessive disease. Main clinical features in- sented with a regressive neurologic process. Four pa- clude silver-leaden hair, bronze skin after sun expo- tients died between 6 months and 3 years after the onset sure, and neurologic involvement (seizures, severe hy- of neurologic dysfunction. One patient showed charac- potonia, and mental retardation). Large granules of teristic ultrastructural findings of Elejalde syndrome. melanin unevenly distributed in the hair shaft are ob- served. Abnormal melanocytes and melanosomes and ab- Conclusions: Elejalde syndrome is different from Che´- normal inclusion bodies in fibroblasts may be present. diak-Higashi and Griscelli syndrome and is character- Differential diagnosis with Che´diak-Higashi syndrome ized by silvery hair and frequent occurrence of fatal neu- and Griscelli syndrome must be done. rologic alterations. Psychomotor impairment may have 2 forms of presentation: congenital or infantile. Al- Observations: We studied pediatric patients with sil- though Elejalde syndrome and Griscelli syndrome are very hair and profound neurologic dysfunction. Im- similar, the possibility that they are 2 different diseases, mune impairment was absent. Age of onset of neuro- although probably allelic related, is suggested. logic signs ranged from 1 month to 11 years; the signs included severe muscular hypotonia, ocular alterations, Arch Dermatol. 1999;135:182-186 ILVERY hair was first recog- distribution of melanin in small and large nized as a pathologic feature clumps irregularly arranged along the hair in Che´diak-Higashi syn- shaft was observed. No accelerated phase drome (CHS).1-3 Oculocuta- has been reported in these patients but re- neous hypopigmentation and current infections and early death are the silvery-gray hair, a marked defective che- usual outcomes. S 5 motaxis of neutrophils, and an apparent In 1979, Elejalde et al first de- association with lymphoid malignancy scribed 3 consanguineous families as hav- characterize this rare autosomal reces- ing neuroectodermal melanolysosomal dis- sive disorder. The diagnosis is usually ease (NEMLD). The main features were an based on the presence of pathogno- autosomal recessive heredity character- monic, anomalous giant cytoplasmic gran- ized by silvery hair, profound dysfunc- ules in neutrophils and in a wide variety tion of the central nervous system, abnor- of other granule-containing cells. Mela- mal melanocytes and melanosomes, and nin in the hair shaft is abnormally distrib- abnormal inclusion bodies in fibroblasts uted in multiple small clumps with a regu- and other cells. Apparently ignoring Ele- lar pattern. Death occurs at an early age, jalde’s description, in recent years sev- following an “accelerated phase” after eral articles have been published describ- From the Departments which infections and/or lymphomalike or- ing patients with the combination of silvery of Dermatology gan infiltration occurs.3 hair and neurologic involvement with- (Drs Duran-McKinster, In 1978, Griscelli et al4 described a out giant cytoplasmic granules or immu- de la Luz Orozco-Covarrubias, different condition characterized also by nologic dysfunction and classifying them Tamayo, and Ruiz-Maldonando) 6 and Pathology silvery-gray hair associated with a pro- as having the following diseases: CHS, (Drs Rodriguez-Jurado and foundly disturbed B-cell and T-cell im- Griscelli disease with cerebral involve- Ridaura), National Institute of munity. No abnormal cytoplasmic gran- ment,7 and Griscelli disease with neuro- Pediatrics, Mexico City, Mexico. ules were present in leukocytes. A different logical involvement.8 Unlike CHS and ARCH DERMATOL / VOL 135, FEB 1999 182 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 Table 1. Clinical Features* PATIENTS AND METHODS Patient Age at Onset Parents’ Ophthalmological No./Sex of First Signs Consanguinity Examination Results From February 1971 to January 1997, all clinical records 1/M 1 mo Negative Nystagmus, esotropia of patients with silvery hair seen at the Department of 2/F 3 y Negative Nystagmus, Dermatology of the National Institute of Pediatrics were hypopigmented retina reviewed. Clinical and pathological findings of our pa- 3/F 11 y† Positive Diplopia, papilledema tients were compatible with CHS in 6 cases, GS in 2 cases, 4/M 2 mo† Positive Congenital amaurosis, and Elejalde syndrome in 7 cases. Patients with silvery hypopigmented papilla hair and neurologic involvement were selected for this 5/M 1 mo Negative Pupillar areflexia study. The following data were collected: sex, age, pa- 6/F 6 y Positive Diplopia rental consanguinity and family history, age of onset of 7/F 1 mo† Negative Congenital amaurosis neurologic alterations, ophthalmologic examination, clinicalandneurologicfeatures,andfollow-up.Datafrom *Allpatients had bronzed skin color and silver-gray hair color. the following laboratory tests were recorded: complete †With other family members affected. peripheral blood cell count from the 6 patients and bone marrow aspirate from 3. Immunologic studies in all pa- tients included serum IgG, IgA, and IgM. Antinuclear antibodies, complement, and phagocytic function were tested with nitroblue tetrazolium. Cell-mediated immu- nity was evaluated by delayed hypersensitivity skin tests with phytohemagglutinin, concanavalin A, Candida, and purified protein-derivative (tuberculin) antigens as well as with T-lymphocyte subsets. Isohemagglutinin anti- body titers against blood groups were obtained in pa- tients 1 and 2. A complete neurologic examination was per- formed by an experienced pediatric neurologist in all of the patients. Specific studies included the follow- ing: electroencephalogram, cerebrospinal fluid analy- sis, and visual- and auditory-evoked potentials. Ce- rebral tomographic scan and magnetic resonance imaging were performed for 5 patients. Skin biopsy specimens from the arm or leg were obtained from each patient, and sections were made for light mi- croscopy in all patients and for transmission elec- tron microscopy in 2 (patients 3 and 6). Samples of hair were obtained from all of the pa- tients and parents for light microscopic examination. Figure 1. Characteristic bronzed skin color and silvery hair in scalp, eyelashes, and eyebrows in Elejalde syndrome (patient No. 4). Griscelli syndrome (GS), NEMLD does not exhibit de- scalp and body hair, eyebrows, and eyelashes had a sil- fects in cellular or humoral immunity but a severe im- very color (Figure 1). Skin and hair color of the pa- pairment of the central nervous system. tients contrasted with the dark skin and black hair of fam- Herein, we describe 7 patients with NEMLD (Ele- ily members. Samples of the hair observed by light jalde syndrome) seen in the National Institute of Pedi- microscopy showed the same characteristics in the 7 pa- atrics of Mexico. tients, consisting of an abnormal distribution of mela- nin in small and large clumps, irregularly distributed along RESULTS the hair shaft with no other abnormalities. A complete ophthalmologic examination showed a wide spectrum of The results of the general features are summarized in abnormalities (Table 1). Table 1. The patients’ age at onset of neurologic signs Che´diak-Higashi syndrome and GS were excluded ranged from l month to 11 years (mean age, 3 years). All in the analysis of our patients for the following reasons: patients were born at term after an uneventful preg- there was no clinical or laboratory evidence of immuno- nancy and normal delivery. Consanguinity of the par- logic impairment and abnormal giant intracytoplasmic ents (first or second cousins) was reported in 3 patients. granules in neutrophils could not be found in periph- Three patients had other family members (2 cousins in eral blood smears or in bone marrow aspirates in pa- patient 3, a brother in patient 4, and 2 sisters in patient tients 5, 6, and 7. Patient 6 had the only blood cell count 7) with silvery hair. They had died in the first decade of with persistent leukopenia. Humoral and cellular immu- life following a regressive neurologic process. nologic test results were within normal limits in all cases. In all patients, the physical examination revealed a Neurologic alterations were the most striking features lighter skin color in covered areas that contrasted with (Table 2). The 4 youngest patients (patients 1, 4, 5, and the patient’s bronzed skin on sunlight-exposed areas. The 7) were severely mentally retarded since the first months ARCH DERMATOL / VOL 135, FEB 1999 183 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 Table 2. Neurologic Features* Neuromuscular Alterations Patient Mental No. Initial Progression Seizures Development Electroencephalogram 1 Hypotonia Spastic quadriparesis Yes Severely retarded Normal 2 Hypotonia Flaccid quadriplegia Yes Regressive