ALPK1- Related Autoinflammatory Disease

Excerpt

Clinical characteristics: ALPK1-related autoinflammatory disease (ALPK1-AD) is characterized by clinical findings that can include intraocular inflammation, retinal degeneration, recurrent fever, deforming arthritis, and headaches. Anhidrosis/hypohidrosis, dental caries, short dental roots, and hyposalivation are common. While most adults have ophthalmologic manifestations, vision loss is not universal. Although significant intrafamilial variability can occur, most individuals with ALPK1-AD exhibit at least one clinical or laboratory feature (such as episodic low-grade fever or episodic elevation of serum markers of inflammation such as C-reactive protein). To date, 41 individuals from 19 families with a pathogenic variant in ALPK1 have been described.

Diagnosis/testing: The diagnosis of ALPK1-AD is established in a proband with suggestive findings and a heterozygous pathogenic variant in ALPK1 identified by molecular genetic testing.

Management: Treatment of manifestations: Supportive treatment involves the following: intraocular inflammation management; low vision services; systemic inflammation management (such as a rheumatologist); dental care of enamel defects; and orthodontic procedures for individuals with short dental roots.

Surveillance: Regular monitoring by specialists treating the ophthalmologic findings, systemic inflammatory disease, and systemic and dental manifestations of anhidrosis/hypohidrosis.

Genetic counseling: ALPK1-AD is inherited in an autosomal dominant manner. If a parent of the proband has the ALPK1 pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. Once the ALPK1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.