GeneReviews((R))-/-? 1993[]; ? (?): ? PMID41343688show ga
CLINICAL CHARACTERISTICS: FASTKD2-related combined oxidative phosphorylation deficiency (FASTKD2-COXPD) is a multisystem disorder that can present from infancy to adulthood with developmental delay with regression that is often triggered by febrile illness and/or seizures. Additional neurologic findings include movement disorder, episodes of acute encephalomyopathy, abnormal muscle tone, and/or stroke-like episodes. Reported ocular manifestations include optic atrophy, nystagmus, strabismus, and visual impairment. Cardiac abnormalities (hypertrophic cardiomyopathy, arrythmia) and impaired kidney function (chronic kidney disease / acute kidney failure) with or without neurologic manifestations have been reported. DIAGNOSIS/TESTING: The diagnosis of FASTKD2-COXPD is established in a proband with suggestive findings and biallelic pathogenic variants in FASTKD2 identified by molecular genetic testing. MANAGEMENT: Treatment of manifestations: Routine outpatient treatment includes developmental and educational support; standard treatment of seizures and movement disorder by an experienced neurologist; physical therapy and orthopedic rehabilitation for hypotonia and spasticity; medical and surgical therapies as needed for spasticity; treatment of ocular manifestations per experienced ophthalmologist with referral to early intervention services and community vision services; standard treatment of cardiomyopathy and arrhythmias; management of kidney disease per nephrologist; treatment for musculoskeletal manifestations per orthopedist; management of hearing loss per otolaryngologist; develop transitional care plan; social work support and coordination of care. Emergency outpatient treatment for mildly increased catabolism includes oral feeds if not vomiting, carbohydrate supplementation, and hydration; antipyretics for fever and/or inflammation; antiemetics for occasional vomiting; prompt empiric antibiotics/antiviral therapy guided by suspected infection. Acute inpatient treatment includes intravenous glucose for increased catabolism and hypoglycemia with cofactor supplementation; standard treatment for neurologic manifestations; management of cardiomyopathy per cardiologist; ventilatory support as needed for respiratory compromise; treatment of multiorgan failure per intensivist including assessment for infection, laboratory assessment for thyroid, liver, and kidney dysfunction, and evidence of myopathy. Surveillance: Assessment of developmental progress, educational needs, neurologic manifestations, growth, and nutritional status at each visit or as clinically indicated; ophthalmology evaluation every six to 12 months or as recommended by ophthalmologist; blood pressure annually or as clinically indicated; EKG and echocardiogram annually or as clinically indicated in those with cardiac disease; kidney function tests and abdominal ultrasound annually or as clinically indicated especially in those with electrolyte imbalance and proteinuria; complete blood count, liver function tests, and liver transaminases annually or as clinically indicated; audiology evaluation every one to two years or as clinically indicated; assess family needs and provide family education at each visit. Agents/circumstances to avoid: Avoid sodium valproate; other drugs should be used with caution (statins, metformin, high-dose acetaminophen, aminoglycosides, linezolid, tetracycline, azithromycin, and erythromycin); anesthesia can aggravate respiratory manifestations and precipitate respiratory failure; avoid propofol; catabolism should be prevented; medication dose adjustment is needed in those with kidney impairment; avoid neuromuscular-blocking drugs in individuals with muscle disease; avoid lactate-containing agents (e.g., Ringer lactate); exercise programs require cardiac clearance in those with hypertrophic cardiomyopathy, exercise intolerance, or exercise-induced rhabdomyolysis. Evaluation of relatives at risk: Clarify the genetic status of apparently asymptomatic older and younger at-risk sibs of an affected individual in order to identify as early as possible those who would benefit from avoidance of agents/circumstances that may further impair mitochondrial function and who may be at risk for seizures (including status epilepticus), acute metabolic decompensation, and other system involvement. GENETIC COUNSELING: FASTKD2-COXPD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a FASTKD2 pathogenic variant, each sib of an affected individual has at conception 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 FASTKD2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.
GeneReviews((R))-/-? 1993 ; ? (?): ?
