Methylmalonic aciduria (cblF): Case report and response to therapy

Waggoner, Darrel; Ueda, Kosei; Mantia, Claudia La; Dowton, S. Bruce

doi:10.1002/(sici)1096-8628(19981012)79:5<373::aid-ajmg8>3.0.co;2-k

Cited by 15 publications

(8 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So far, the cblF defect was diagnosed only in patients originating from Canada, USA, Germany, and The Netherlands (Rutsch et al 2009); this is the first patient of Turkish origin. Furthermore, in three previously described patients, congenital heart defects were reported, including atrial septal defect, patent ductus arteriosus (Rutsch et al 2009, case 6), right dominant atrioventricular septal defect with common atrium and double-outlet right ventricle (Rutsch et al 2009, case 1) and an apical ventricular septal defect (Waggoner et al 1998). These clinical features, which are common in other defects of intracellular cobalamin metabolism, were also present in our patient.…”

Section: Discussionsupporting

confidence: 75%

A novel mutation in LMBRD1 causes the cblF defect of vitamin B₁₂ metabolism in a Turkish patient

Gailus¹,

Suormala

Malerczyk-Aktas

et al. 2010

J of Inher Metab Disea

View full text Add to dashboard Cite

In the cblF defect of vitamin B(12) (cobalamin) metabolism, cobalamin is trapped in lysosomes. Consequently, cobalamin coenzyme synthesis is blocked, and cofactors for methionine synthase and methylmalonyl-coenzyme A (CoA) mutase are deficient. We recently identified LMBRD1 as the causative gene located on chromosome 6q13 and showed that 18 out of 24 alleles in unrelated patients carried the deletion c.1056delG (p.L352fsX18) (Rutsch et al. (Nat Genet 41:234-239, 2009). LMBRD1 encodes the lysosomal membrane protein LMBD1, which presumably facilitates lysosomal cobalamin export. Our patient is the second child of consanguineous Turkish parents. He presented on the second day of life with cerebral seizures due to intraventricular hemorrhage. Plasma homocysteine and urinary methylmalonic acid levels were elevated, and serum cobalamin level was decreased. Synthesis of both cobalamin coenzymes was deficient in cultured skin fibroblasts. The cblF defect was confirmed by somatic complementation analysis. Sequencing of LMBRD1 revealed the novel deletion c.1405delG (p.D469fsX38) on both alleles. Real-time polymerase chain reaction (PCR) revealed reduced messenger RNA (mRNA) levels in patient fibroblasts compared with controls. Transfection of patient fibroblasts with the LMBD1 wild-type complement DNA (cDNA) rescued coenzyme synthesis and function, confirming this new deletion as an additional cause of the cblF defect. This case adds to the spectrum of clinical presentations and mutations of this rare disorder of lysosomal transport.

show abstract

Section: Discussionsupporting

confidence: 75%

A novel mutation in LMBRD1 causes the cblF defect of vitamin B₁₂ metabolism in a Turkish patient

Gailus¹,

Suormala

Malerczyk-Aktas

et al. 2010

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…At the same time, the natural gastric barrier decreases with consequent risk of gastrointestinal bacterial overgrowth and competing for the use of ingested Cbl [69]. If rare genetic defects of cellular trafficking and processing proteins exist, the choice of alternative forms of Cbl, such as Me-Cbl or H-Cbl could improve the effectiveness of supplementation [154,208,209,210]. It was speculated that the use of Cn-Cbl is unsuitable for supplementation among smokers, because it represents a form preferentially excreted for the purpose of hydrocyanic acid removal [211,212].…”

Section: Discussionmentioning

confidence: 99%

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

Rizzo¹,

et al. 2016

View full text Add to dashboard Cite

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.

show abstract

“…We present a new case of cblF disorder, presenting in an atypical manner with a prominent metopic suture, cleft palate, unilateral renal agenesis, feeding difficulties, and early liver abnormalities, which was diagnosed late by the use of WES. To date, a total of 15 cases have been reported in the literature [ Rosenblatt et al, 1986 ; Shih et al, 1989 ; MacDonald et al, 1992 ; Wong et al, 1992 ; Waggoner et al, 1998 ; Rutsch et al, 2009 ; Gailus et al, 2010 ; Miousse et al, 2011 ; Oladipo et al, 2011 ] in addition to a recent case of combined cblF/cblG disorder suggestive of digenic inheritance [ Farwell Gonzalez et al, 2015 ]. The typical clinical phenotype of cblF disorder is failure to thrive and feeding difficulties, developmental delay and haematological features including megaloblastic anaemia, neutropaenia and thrombocytopaenia (table 2 ).…”

Section: Discussionmentioning

confidence: 99%

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

Constantinou¹,

D’Alessandro²,

Lochhead³

et al. 2015

Mol Syndromol

View full text Add to dashboard Cite

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.

show abstract

Methylmalonic aciduria (cblF): Case report and response to therapy

Cited by 15 publications

References 5 publications

A novel mutation in LMBRD1 causes the cblF defect of vitamin B₁₂ metabolism in a Turkish patient

A novel mutation in LMBRD1 causes the cblF defect of vitamin B₁₂ metabolism in a Turkish patient

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

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

Contact Info

Product

Resources

About

Methylmalonic aciduria (cblF): Case report and response to therapy

Cited by 15 publications

References 5 publications

A novel mutation in LMBRD1 causes the cblF defect of vitamin B12 metabolism in a Turkish patient

A novel mutation in LMBRD1 causes the cblF defect of vitamin B12 metabolism in a Turkish patient

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

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

Contact Info

Product

Resources

About

A novel mutation in LMBRD1 causes the cblF defect of vitamin B₁₂ metabolism in a Turkish patient

A novel mutation in LMBRD1 causes the cblF defect of vitamin B₁₂ metabolism in a Turkish patient