Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

Carrillo-Carrasco, Nuria; Chandler, Randy J.; Venditti, Charles P.

doi:10.1007/s10545-011-9364-y

Cited by 189 publications

(281 citation statements)

References 96 publications

(150 reference statements)

Supporting

Mentioning

265

Contrasting

Unclassified

Order By: Relevance

“…More specific analyses, such as biochemical and molecular testing, can determine the specific deficiency and associated mutations. 3,14,18 Sequencing the gene (MMACHC located at 1p34.1 12 ) for the most common complementation group (cblC) confirmed our diagnosis.…”

Section: Discussionsupporting

confidence: 69%

“…The disorder is suspected in infants presenting with failure to thrive, developmental delay, seizures, and acidosis. 3,5,14 In contrast, the only unifying characteristic in older patients with cblC deficiency is varying degrees of neuropsychiatric symptoms. 5 Ataxia with cerebellar findings on magnetic resonance imaging, as was found in this patient, has only been reported in 1 previous case.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Betaine increases remethylation of homocysteine to methionine. 1,14 The addition of folate may also help with remethylation, but no longitudinal studies have documented this. 14 Protein restriction is occasionally used, although its benefits have not been clearly proven.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with early-onset, however, late-onset cases are more likely to have a better prognosis if diagnosed and treated. 5,14,15 We report a case of an adolescent girl who presented with psychosis and anorexia and later developed seizures and ataxia due to cblC deficiency. Treatment with hydroxocobalamin, betaine, and folate resulted in biochemical and clinical improvement.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

Rahmandar¹,

Bawcom²,

Romano

et al. 2014

Pediatrics

View full text Add to dashboard Cite

Although cobalamin (cbl) C deficiency is the most common inherited disorder of vitamin B12 metabolism, the late-onset form of the disease can be difficult to recognize because it has a broad phenotypic spectrum. In this report, we describe an adolescent female exposed to unknown illicit substances and sexual abuse who presented with psychosis, anorexia, seizures, and ataxia. The patient’s diagnosis was delayed until a metabolic workup was initiated, revealing hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria. Ultimately, cblC deficiency was confirmed when molecular testing showed compound heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and folate, which resulted in improvement of her clinical symptoms and laboratory values. This patient demonstrates a previously unrecognized presentation of late-onset cblC deficiency. Although neuropsychiatric symptoms are common in late-onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia has not been previously described in these patients. This case emphasizes that inborn errors of metabolism should be part of the differential diagnosis for a teenager presenting with altered mental status, especially when the diagnosis is challenging or neurologic symptoms are unexplained. Correct diagnosis of this condition is important because treatment is available and can result in clinical improvement.1

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

Rahmandar¹,

Bawcom²,

Romano

et al. 2014

Pediatrics

View full text Add to dashboard Cite

show abstract

“…Only one of the five patients had elevated blood MMA and homocysteine levels. Compound heterozygous patients carrying the c.482G>A mutation with an early-onset mutation (e.g., c.271dupA) have a milder phenotype than patients with homozygous early-onset mutations (Morel et al 2006;Carrillo-Carrasco et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine Level

et al. 2015

View full text Add to dashboard Cite

Cobalamin C (CblC) disease is the most common inherited disorder of intracellular cobalamin metabolism. It is a multisystemic disorder mainly affecting the eye and brain and characterized biochemically by methylmalonic aciduria, low methionine level, and homocystinuria. We report a patient found to have CblC disease who initially presented with low carnitine and normal propionylcarnitine (C3) levels on newborn screen. Newborn screening likely failed to detect CblC in this patient because of both his low carnitine level and the presence of a mild phenotype.

show abstract

VitaminB₁₂: Disorders of Absorption and Metabolism

Watkins

Rosenblatt

2017

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Derivatives of vitamin B 12 (cobalamin) are required for activity of two enzymes: methylmalonyl‐CoA mutase, which catalyses conversion of methylmalonyl‐CoA to succinyl‐CoA, and methionine synthase, which converts homocysteine to methionine. Cobalamin deficiency results in the accumulation of methylmalonic acid and homocysteine in blood and urine. Clinically, deficiency results in megaloblastic anaemia and subacute combined degeneration of the spinal cord, loss of sensation, ataxia, dementia and psychosis. Dietary cobalamin deficiency is rare in developed countries, except for individuals consuming a vegan diet. A more common cause of cobalamin deficiency is pernicious anaemia, an autoimmune disease that results in inability to absorb cobalamin from the intestine. A number of rare genetic disorders have been identified that result in either failure to absorb dietary cobalamin, to transport cobalamin from the intestine to cells that require it for metabolism or to convert intracellular cobalamin to one or both of its coenzyme derivatives, adenosylcobalamin and methylcobalamin. Key Concepts Cobalamin (vitamin B 12 ) is required for activity of two enzymes, methylmalonyl‐CoA mutase and methionine synthase, in mammalian cells. Cobalamin deficiency results in accumulation of methylmalonic acid and homocysteine in blood and urine. Clinically, deficiency is characterised by megaloblastic anaemia and/or neurological problems. Uptake of dietary cobalamin requires the binding protein intrinsic factor, secreted by parietal cells of the stomach, and the intestinal receptor cubam. Autoimmune destruction of parietal cells results in pernicious anaemia. Mutations in the genes encoding intrinsic factor or the components of cubam (cubilin and amnionless) result in heritable cobalamin malabsorption and signs of cobalamin deficiency. Peripheral cells take up cobalamin bound to the transport protein transcobalamin by carrier‐mediated endocytosis. Cells convert cobalamin to adenosylcobalamin, required by methylmalonyl‐CoA mutase, and methylcobalamin, required by methionine synthase. Rare mutations affecting genes involved in cobalamin metabolism result in decreased synthesis of either or both cobalamin derivatives. Mutations in certain transcription regulators can affect expression of genes encoding cobalamin metabolising enzymes, resulting in altered cobalamin coenzyme synthesis.

show abstract

Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

Cited by 189 publications

References 96 publications

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine Level

VitaminB₁₂: Disorders of Absorption and Metabolism

Contact Info

Product

Resources

About

Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

Cited by 189 publications

References 96 publications

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine Level

VitaminB12: Disorders of Absorption and Metabolism

Contact Info

Product

Resources

About

VitaminB₁₂: Disorders of Absorption and Metabolism