Silvery-Gray Hair in a Newborn FREE

A term newborn, born via spontaneous vaginal delivery, had abnormally light skin and silvery hair that is dark at the roots and light at the tips (Figure 1). Both parents are of Hispanic descent and have black hair and dark skin, as do their 2 other living children. Their first child had similar silvery hair and died at 3 months of age, 1 week after developing a fever and intractable seizures. An investigation was not done for cause of death due to the rapidity of the child's decline. The mother received prenatal care, took only prenatal vitamins, and never had a spontaneous abortion. The parents' family histories are otherwise unremarkable and there is no consanguinity. The remainder of the physical examination, including the ophthalmologic and neurologic examination, is unremarkable. Laboratory results including a complete blood cell count, peripheral blood smear, white blood cell morphology, liver panel, and coagulation studies including bleeding study are normal.

Griscelli syndrome

C. Light microscopy of hair

The key clinical feature of this case is the limited differential diagnosis of partial oculocutaneous albinism. The markedly abnormal hair in an otherwise asymptomatic neonate requires further workup to rule out genetic syndromes with life-threatening consequences that could be avoided with treatment.

Griscelli syndrome is a rare autosomal recessive disorder characterized by partial oculocutaneous albinism and a silvery-gray sheen of the hair with large pigment aggregates of melanosomes within melanocytes in hair shafts. Griscelli syndrome type 1 (OMIM # 214450), caused by mutations in MYO5A, is associated with primary neurologic deficits without immunologic abnormalities such as hypogammaglobulinemia. Griscelli syndrome type 2 (OMIM # 607624), caused by mutations in RAB27A, is associated with immunologic dysfunction with uncontrolled T-lymphocyte and macrophage activation leading to hemophagocytic lymphohistiocytosis. Griscelli syndrome type 2 has no primary neurologic impairment unless lymphocyte infiltration into the nervous system occurs. Griscelli syndrome type 3 (OMIM # 609227) is isolated oculocutaneous albinism without neurologic or immunologic complications and is caused by mutations in the melanophilin gene.

RAB27A encodes for a small GTPase protein found in both melanocytes and lymphocytes that is essential for release of lytic granules from lymphocytes.¹ Hemophagocytic lymphohistiocytosis is a syndrome of inappropriate immune activation that often is triggered by infection and represents an accelerated phase of disease with lymphocytic infiltration of almost all organs leading to a sepsis-like presentation and death. Treatment with hematopoietic stem cell transplant is considered curative and should be performed prior to the infant's entering the accelerated phase of the disease.²

In this patient, the death of a sibling with similar physical findings should prompt a thorough investigation. Timely confirmation of the diagnosis is critical so treatment may be initiated. Light microscopy examination of a hair shaft can facilitate a quick diagnosis. Abnormal conglomerate of pigment visualized within the hair shaft (Figure 2) is characteristic of Griscelli syndrome. The differential diagnosis includes oculocutaneous albinism, Hermanksy-Pudlak syndrome, and Chediak-Higashi syndrome. All patients with albinism should avoid direct exposure to UV radiation; however, this will not help with diagnosis. Visual evoked potentials have a characteristic pattern in oculocutaneous albinism; however, the normal ophthalmologic findings exclude this diagnosis. Chromosome analysis does not play a role in the diagnosis of albinism.

Oculocutaneous albinism is the most common form of albinism.³ Patients have white hair, pink to brown eyes, and white to light brown skin. Diagnosis is made by characteristic eye findings including hypopigmentation, foveal hypoplasia, nystagmus, and alternating strabismus. Nerve fibers from the temporal side of the retina cross to the contralateral hemisphere causing loss of binocular vision and depth perception with characteristic patterns on visual evoked potentials that confirm the diagnosis.⁴

Chediak-Higashi syndrome (OMIM # 214500) is an autosomal recessive condition related to mutations in LYST, resulting in accumulation of vesicular contents in various cells. Diagnosis is made by visualization of the pathognomonic giant peroxidase-positive cytoplasmic granules in neutrophils, resulting in recurrent bacterial skin and upper respiratory tract infections. Melanin in melanocytes is not distributed to keratinocytes, leading to albinism. As in Griscelli syndrome, patients with Chediak-Higashi syndrome can enter an accelerated phase with hemophagocytic lymphohistiocytosis, often leading to death despite treatment.⁵

Hermanksy-Pudlak syndrome is an autosomal recessive disorder caused by mutations in heterogeneous genes related to membrane and protein trafficking and function. Patients classically have oculocutaneous albinism and a bleeding diathesis. Lysosomal accumulation of ceroid-like material may be responsible for the progressive pulmonary fibrosis and inflammatory bowel disease seen in adolescents and young adults.^5- 6

The patient was transferred within 2 weeks of birth to a bone marrow transplant center and received stem cell transplantation at 5 months of age. The patient is 8 months old and well.