Clinical characteristics: CLPB (caseinolytic peptidase B) deficiency is characterized by neurologic involvement and neutropenia, which range from severe to mild. To date, a total of 26 individuals from 16 families have been reported.
Diagnosis/testing: The diagnosis of CLPB deficiency is established in a proband with one or more suggestive clinical and/or imaging findings and/or elevated urinary excretion of 3-methylglutaconic acid (3-MGA), and identification of biallelic pathogenic variants in CLPB on molecular genetic testing.
Management: Treatment of manifestations: Treatment is largely supportive. A multidisciplinary team including a metabolic physician, pediatric neurologist, developmental pediatrician, dietitian, physical therapist, and rehabilitation specialist is recommended. No specific dietary or metabolic treatment is available. Thorough developmental assessment is indicated for all children with cognitive difficulties to tailor special education services. Early intervention may include physical therapy, occupational therapy, and/or speech therapy. Treatment of the neurologic manifestations is per current clinical practice based on the findings. Granulocyte-colony stimulating factor (G-CSF) can be used to increase neutrophil counts to reduce the frequency of infections, especially in individuals with the mild or moderate phenotype. Surveillance: Neurologic, ophthalmologic, immunologic/hematologic, and orthopedic evaluations are based on individual findings as needed. Agents/circumstances to avoid: Drugs potentially toxic to mitochondria, including chloramphenicol, aminoglycosides, linezolide, valproic acid, and nucleoside reverse transcriptase inhibitors.
Genetic counseling: CLPB deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the CLPB pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic diagnosis are possible.
Copyright © 1993-2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.