Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism (OCA), immunodeficiency, a mild bleeding tendency, and late adolescent- to adult-onset neurologic manifestations (e.g., learning difficulties, peripheral neuropathy, ataxia, and parkinsonism). While present in nearly all individuals with CHS, these clinical findings vary in severity. Of note, all individuals with CHS are at risk of developing neurologic manifestations and hemophagocytic lymphohistiocytosis (HLH). Individuals with severe childhood-onset presentations are considered to have "classic" CHS, whereas individuals with milder adolescent- to adult-onset presentations are considered to have "atypical" CHS. Because of the considerable overlap between classic CHS and atypical CHS, the disorder is best understood as a continuum of severe to milder phenotypes, with the universal feature being the pathognomonic giant granules within leukocytes observed on peripheral blood smear.

Arylsulfatase A deficiency (also known as metachromatic leukodystrophy or MLD) is characterized by three clinical subtypes: late-infantile, juvenile, and adult MLD. The age of onset within a family is usually similar. The disease course may be from several years in the late-infantile-onset form to decades in the juvenile- and adult-onset forms. Late-infantile MLD: Onset is before age 30 months. Typical presenting findings include weakness, hypotonia, clumsiness, frequent falls, toe walking, and dysarthria. Language, cognitive, and gross and fine motor skills regress as the disease progresses. Later signs include spasticity, pain, seizures, and compromised vision and hearing. In the final stages, children have tonic spasms, decerebrate posturing, and general unawareness of their surroundings. Juvenile MLD: Onset is between age 30 months and 16 years. Initial manifestations include a decline in school performance and the emergence of behavioral problems, followed by gait disturbances. Progression is similar to but slower than in the late-infantile form. Adult MLD: Onset occurs after the age of 16 years, sometimes not until the fourth or fifth decade. Initial signs can include problems in school or job performance, personality changes, emotional lability, or psychosis; in others, neurologic symptoms (weakness and loss of coordination progressing to spasticity and incontinence) or seizures predominate initially. Peripheral neuropathy is common. The disease course is variable, with periods of stability interspersed with periods of decline, and may extend over two to three decades. The final stage is similar to earlier-onset forms.