A New, Atypical Case of Cobalamin F Disorder Diagnosed by Whole Exome Sequencing

Abstract

Cobalamin F (cblF) disorder, caused by homozygous or compound heterozygous mutations in the LMBRD1 gene, is a recognised cause of developmental delay, pancytopaenia and failure to thrive which may present in the neonatal period. A handful of cases have been reported in the medical literature. We report a new case, diagnosed at the age of 6 years through whole exome sequencing, with atypical features including prominent metopic suture, cleft palate, unilateral renal agenesis and liver abnormalities, which broaden the phenotypic spectrum.

Vitamin B12 deficiency secondary to cobalamin F deficiency simulating dyskeratosis congenita

“… 10 Classically, CblF deficiency is diagnosed with a high index of suspicion alongside urine organic acid and plasma analysis. 1 In our patient, WES was needed to establish the diagnosis because of the unusual presentation of unique diffuse dyschromia involving the palms and soles, diffuse finger and toenail hyperpigmentation, and graying of the scalp hairs, which were suggestive of reticulated and dyspigmentation genodermatosis, particularly dyskeratosis congenita, especially when one considers the accompanying microcephaly and hematologic features. However, the early onset of symptoms, lack of oral leukoplakia, and nail dystrophy combined with a marked improvement in response to cobalamin replacement therapy and confirmatory testing with WES, assisted in negating this differential diagnosis.…”

“…Cobalamin (vitamin B12) is a water-soluble vitamin that is obtained from animal sources. 1 It plays important roles in development, growth, and cellular differentiation. 3 Although deficiency of the vitamin is primarily an adult disease caused by gastrointestinal and malabsorptive disorders, it is now more frequently encountered in children who are born in strictly vegetarian households or who have a mutation in one of the genes associated with the vitamin's intrinsic pathways.…”

“…However, the early onset of symptoms, lack of oral leukoplakia, and nail dystrophy combined with a marked improvement in response to cobalamin replacement therapy and confirmatory testing with WES, assisted in negating this differential diagnosis. 1 …”

“…Cobalamin F (CblF) deficiency is part of a rare group of intracellular vitamin B12 metabolism deficiencies. 1 It most commonly presents during infancy and childhood, and it manifests as a broad spectrum of phenotypes that include developmental, neurologic, hematologic and, rarely, dermatologic symptoms involving the skin and its appendages. 2 Only a few cases have been reported worldwide.…”

Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes

“…The clinical phenotype is variable comprising small for gestational age, poor feeding, failure to thrive and developmental delay. Interestingly, 7 out of 15 children had CHD or laterality defects (Supplementary Table 1 ) [ 17 – 19 ]. In the present study, metabolic analysis of individual HET11_501 did not show any abnormalities.…”