Subject(s)
4-Hydroxyphenylpyruvate Dioxygenase/antagonists & inhibitors , Cyclohexanones/therapeutic use , Enzyme Inhibitors/therapeutic use , Nitrobenzoates/therapeutic use , Pregnancy Complications/drug therapy , Tyrosinemias/drug therapy , Adolescent , Combined Modality Therapy/adverse effects , Contraindications , Cyclohexanones/adverse effects , Enzyme Inhibitors/adverse effects , Female , Humans , Nitrobenzoates/adverse effects , Phenylalanine , Pregnancy , Pregnancy Complications/diet therapy , Term Birth , Tyrosine , Tyrosinemias/diet therapyABSTRACT
The cobalamin F (cblF) defect is caused by disturbed lysosomal release of cobalamin (vitamin B(12)) into the cytoplasm caused by mutations in the LMBRD1 gene. We present the clinical and biochemical characterization of a patient with newly diagnosed cblF disease and a follow-up on a 14-year-old patient. The new patient presented with elevation of propionyl carnitine found on a newborn screen. The patient was small for gestational age, exhibited dysmorphic features and mild developmental delay, and had trigonocephaly and ventricular septal defect. There was biochemical normalization and clinical improvement within 3 weeks of parenteral cobalamin treatment. The other patient presented at 4 weeks of life with failure to thrive and feeding difficulties. She was treated only with monthly cyanocobalamin shots. The patient has never experienced metabolic decompensation. She had short stature and was an average student with no behavioral concerns. Her metabolic derangements normalized after switching to weekly hydroxycobalamin. The available data on 14 patients with confirmed cblF disease suggest variability in age of onset, presenting symptoms, response to treatment, and long-term complications. Common clinical findings include small for gestational age, feeding difficulties, growth failure, and developmental delays. Some patients have congenital heart defects, dysmorphic features, and other congenital anomalies.
Subject(s)
Nucleocytoplasmic Transport Proteins/genetics , Vitamin B 12 Deficiency/genetics , Adolescent , Female , Follow-Up Studies , Humans , Infant, Newborn , Mutation , PhenotypeSubject(s)
Amino Acid Metabolism, Inborn Errors/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Lysine/blood , Amino Acid Metabolism, Inborn Errors/complications , Amino Acid Transport System y+L , Child, Preschool , Citrulline/administration & dosage , Fusion Regulatory Protein 1, Light Chains/genetics , Fusion Regulatory Protein 1, Light Chains/metabolism , Humans , Liver/drug effects , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Lysine/administration & dosage , Male , Mutation , Treatment OutcomeABSTRACT
OBJECTIVE: To describe patient selection, treatment administration, response evaluation, and side effect management associated with sapropterin therapy in infants and children aged <4 years. STUDY DESIGN: Six case reports are presented from 4 US metabolic clinics treating phenylketonuria with sapropterin in patients aged 7 months to 4 years. Outcomes included blood phenylalanine (Phe) levels before and during treatment. For 3 of 6 cases, diet records were used to monitor changes in dietary Phe. RESULTS: Severity of phenylketonuria ranged from mild to severe (classic). Treatment with sapropterin was safe and generally well tolerated. Blood Phe levels were reduced, or maximum dietary Phe tolerance was increased in patients with blood Phe that was well controlled by diet. CONCLUSIONS: Given the increasing evidence that maintaining blood Phe levels below 360 µmol/L is important for the normal development of neurocognitive and behavioral function, sapropterin can be combined with a Phe-restricted diet to control blood Phe levels in young patients responsive to sapropterin therapy.
