Frontotemporal Atrophy: Presenting Sign in Infantile Cobalamin Deficiency (original) (raw)
Related papers
The Turkish Journal of Pediatrics, 2019
Functional methionine synthase deficiency can be separated into two classes, cobalamin (Cbl) deficiency type E (CblE) and type G (CblG), which are the result of mutations that affect methionine synthase reductase or methionine synthase, respectively. Deficiency of methionine synthase activity may result in megaloblastic anemia without methylmalonic aciduria and neuromuscular abnormality of varying severity. Delayed milestones, ataxia, cerebral atrophy, muscular hypotonia, neonatal seizures, and blindness have been reported as the associated clinical findings. Early diagnosis and treatment are crucial for a more favorable diagnosis of the affected cases. Herein we report a three-month-old boy with CblG disease who presented with failure to thrive, chronic diarrhea, feeding intolerance, oral ulcers, microcephaly and hypotonia, and showed a dramatic response to treatment. In the first few months of life, megaloblastic anemia accompanied by apparent neurological involvement should direct physicians to order examinations like measurement of total homocysteine and methylmalonic acid levels to detect possible forms of inherited Cbl intracellular metabolism disorders.
Cobalamin F Disease Detected by Newborn Screening and Follow-up on a 14-Year-Old Patient
PEDIATRICS, 2011
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.
Outcomes of patients with cobalamin C deficiency: A single center experience
JIMD Reports, 2020
Biallelic variants in MMACHC results in the combined methylmalonic aciduria and homocystinuria, called cobalamin (cbl) C (cblC) deficiency. We report 26 patients with cblC deficiency with their phenotypes, genotypes, biochemical parameters, and treatment outcomes, who were diagnosed and treated at our center. We divided all cblC patients into two groups: group 1: SX group: identified after manifestations of symptoms (n = 11) and group 2: NB group: identified during the asymptomatic period via newborn screening (NBS) or positive family history of cblC deficiency (n = 15). All patients in the SX group had global developmental delay and/or cognitive dysfunction at the time of the diagnosis and at the last assessment. Seizure, stroke, retinopathy, anemia, cerebral atrophy, and thin corpus callosum in brain magnetic resonance imaging (MRI) were common in patients in the SX group. Global developmental delay and cognitive dysfunction was present in nine patients in the NB group at the last assessment. Retinopathy, anemia, and cerebral atrophy and thin corpus callosum in brain MRI were less frequent. We report favorable outcomes in patients identified in the neonatal period and treated pre-symptomatically. Identification of cblC deficiency by NBS is crucial to improve neurodevelopmental outcomes.
Cerebral atrophy in 21 hypotonic infants with severe vitamin B12 deficiency
Journal of Paediatrics and Child Health, 2019
Aim: Nutritional B12 deficiency is a treatable cause of neurodevelopmental delay in infants. We report 21 infants with developmental regression and brain atrophy as revealed using cranial magnetic resonance imaging (MRI), secondary to severe vitamin B12 deficiency. Methods: Twenty-one infants aged 4-24 months with B12 deficiencies who were admitted to our clinic between May 2013 and May 2018 were included in the study. MRI, bone marrow aspiration and the Denver-II Developmental Screening Test were performed in all infants. Results: The mean age of the infants was 12.3 months, and the mean B12 level was 70.15 AE 32.15 ng/L. Hypotonia and neurodevelopmental retardation, and anaemia were present in all patients. Their bone marrow examinations were compatible with megaloblastic anaemia. Twelve patients had microcephaly, seven had tremor and one patient died of severe sepsis. Almost all patients were fed with breast milk and their mothers were also malnourished. Nine (42.9%) of the patients were Turkish and 12 (57.1%) were Syrian. All patients had abnormal Denver-II Developmental Screening Test scores. Most patients had severe cortical atrophy, cerebral effusion, thinning of the corpus callosum and delayed myelinisation in cranial MRI. Treatment with B12 resulted in dramatic improvement in general activity and appetite within 72 h. Tremors resolved in all cases. Conclusion: Neurological findings and developmental delay related to nutritional B12 deficiency can be prevented without sequelae if diagnosed early. Screening and treating of mothers for this deficiency will contribute to the health of both the mother and their feeding infant.
Determinants of cobalamin status in newborns
Pediatrics, 2001
Cobalamin deficiency accompanied by bone marrow dysfunction and impaired central nervous system development has been reported in infants who were born to mothers with low cobalamin intake. We investigated the relation between cobalamin status in newborns and in their healthy mothers who consumed an omnivorous diet. Serum cobalamin and the functional markers plasma methylmalonic acid (MMA) and total homocysteine (tHcy) were determined in 173 newborns and their mothers. Forty-five children and mothers were reinvestigated after 6 weeks. At birth, median (interquartile range) serum cobalamin levels were 245 (175-323) pmol/L in the mothers and 314 (238-468) pmol/L in the newborns. In the neonates, serum cobalamin, but not folate, was inversely associated with MMA and tHcy. Among maternal factors, low serum cobalamin was the strongest predictor of impaired cobalamin function (defined as low cobalamin, high tHcy, or high MMA levels) in the newborns. After 6 weeks, the maternal cobalamin le...
Early neurodevelopmental characterization in children with cobalamin C/defect
Journal of Inherited Metabolic Disease, 2019
Cobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism. Developmental delay, behavioral problems, and maculopathy are common, but they have not been systematically investigated. The aim of this study was to define early neurodevelopment in cblC patients and the possible contribution of different factors, such as mode of diagnosis, age at diagnosis, presence of brain lesions and epilepsy. Children up to the age of 4 years with a visual acuity ≥1/10 were evaluated using the Griffiths' Mental Development Scales. Eighteen children were enrolled (age range 12‐48 months). Four were diagnosed by newborn screening (NBS); in the others mean age at diagnosis was 3.5 months (range 0.3‐18 months). Eight had seizures: three in the first year, and five after the second year of life. Fourteen had brain lesions on magnetic resonance imaging (MRI). Neurovisual assessment evidenced low visual acuity (<3/10) in 4/18. NBS diagnosed patients had higher general and...
Cobalamin C Deficiency: Case Report of Two Different Clinical Presentations
Journal of Neurology and Experimental Neuroscience, 2016
Cobalamin C deficiency (CblC) is the most frequent inborn error of cobalamin (Cbl) metabolism, which has a wide clinical spectrum. Cbl C defect causes the accumulation of methylmalonic acid and homocysteine and decreased methionine synthesis. Here we presented two distinct clinical forms of patients with CblC. First patient with early onset form was presented with failure to thrive, mild hypotonia, megaloblastic anemia and leukopenia at 2.5 months old. Second patient was presented with mental status changes, loss of speech, inability to walk and megaloblastic anemia at 12 years old. Laboratory analysis showed hyperhomocysteinemia, low plasma methionine levels and high urinary methylmalonic acid in both patients. Molecular analysis supported the diagnosis of CblC and treatment resulted in improvement of biochemical abnormalities, and neurologic findings in both patients.
Involuntary movements in infantile cobalamin deficiency appearing after treatment
Pediatric Neurology, 2001
Involuntary movements may be a symptom in most infants who present with neurologic syndrome of infantile cobalamin (vitamin B 12 ) deficiency. In this report, two infants with cobalamin deficiency are presented. These patients also developed a striking movement disorder that appeared a few days after treatment with intramuscular cobalamin. The movement disorder was characterized by severe involuntary movements, which were a combination of tremor and myoclonus particularly involving tongue, face, pharynx, and legs. The neurologic symptoms improved within a few days after the administration of clonazepam. In each patient the mother was also cobalamin deficient and the infant was solely breast-fed. The cause of involuntary movements that can appear rarely after treatment in infantile cobalamin deficiency is not known. Besides initial neurologic presenting symptoms of cobalamin deficiency, the occurrence of involuntary movements after treatment should also receive attention. This movement disorder may disappear spontaneously, or an additional treatment may be an alternative approach if the symptoms are severe.