Table 3 Guideline-recommended clinical management changes associated with pathogenic or likely pathogenic mutations

ROH04

TYR

Ophthalmologic evaluations at least annually along with routine skin screening for pre-cancerous lesions due to increased risk for melanoma. Appropriate preparation for sun exposure (sunscreen, glasses, hats, etc). Ongoing clinical trials to evaluate proposed treatment response on cultured melanocytes.

ROH22

PCCB

Management in a metabolic clinic including dietary guidance and supplementation. Screen for cardiomyopathy and cardiac dysfunction. Intravenous provision of glucose and lipids when undergoing acute infection, dehydration, or vomiting. Avoidance of prolonged fasting, excess protein intake, medications that prolong QT interval and neuroleptic antiemetics.

ROH26

SLC25A15

Management in metabolic clinic including dietary guidance (low-protein diet, citrulline supplementation) and use of ammonia scavengers. Avoidance of liver transplantation, prolonged fasting, and valproic acid.

ROH31

NDUFV2

Consideration of mitochondrial treatments/supplementation including riboflavin and screening for hypertrophic cardiomyopathy.

ROH44

TPP1

Seizure medications that may be contraindicated include carbamazepine, phenytoin, lamotrigine. Ongoing clinical trials for recombinant human enzyme therapy, as well as ongoing natural history, genotype-phenotype, and other studies.

ROH52

GJB2

Multidisciplinary management (ex: geneticist, otolaryngologist, deaf educator, etc.) and consideration of cochlear implantation. Avoidance of noise exposure.

ROH23

HBB

Specific treatments (e.g. transfusions, managing related issues such as potential iron overload), can be effective. Mutations may also result in different types of hematologic disease (e.g. Hemolytic anemia), and genetic diagnosis may aid early recognition and treatment (e.g. with RBC transfusion), as well as avoid unnecessary treatments (e.g. splenectomy in Heinz body anemia).

ROH44

OTC

Long-term dietary measures (e.g. decreasing the nitrogen load with low protein diet, use of nitrogen scavengers, and administration of arginine/citrulline) may be beneficial. Certain agents (e.g. valproate, systemic corticosteroids, as well as triggers such as fasting) should be avoided due to the potential of adverse events.