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Three new cases of late-onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy.

Huemer M, Scholl-Bürgi S, Hadaya K, Kern I, Beer R, Seppi K, Fowler B, Baumgartner MR, Karall D - Orphanet J Rare Dis (2014)

Bottom Line: Raising awareness for this disorder can significantly improve patients' outcome and perspective by timely initiation of targeted treatment.Newborn screening (NBS) for the cblC defect might be of benefit especially for late-onset patients since treatment seems efficient when initiated before irreversible organ damage.More specifically, total homocysteine in plasma and methylmalonic acid in urine/plasma should be measured in unexplained neurologic, psychiatric, renal, haematologic and thromboembolic disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolic Diseases and Children's Research Center, University Children's Hospital Zürich, Zürich, Switzerland. martina.huemer@kispi.uzh.ch.

ABSTRACT

Background: The cblC defect is a rare inborn error of intracellular cobalamin metabolism. Biochemical hallmarks are elevated homocysteine and low methionine in plasma accompanied by methylmalonic aciduria. Due to the heterogeneous clinical picture, patients with the late-onset form of the disease (onset >12 months) come to the attention of diverse medical specialists, e.g. paediatricians, neurologists, nephrologists, psychiatrists or haematologists. The report reviews the published clinical data and adds three new cases to raise awareness for this severe but often treatable disease.

Methods: The Pubmed and the Cochrane databases were searched for clinical reports on cblC patients and three unreported cases are presented to illustrate the clinical spectrum.

Results: Reports on 58 cases (30 females, 22 males, 6 = no information) and the three new cases underlined the clinical heterogeneity of the disease. Time between first symptoms and diagnosis ranged from three months to more than 20 years. Haemolytic uraemic syndrome and pulmonary hypertension were main presenting symptoms in preschool children. In older children/adolescents, psychiatric symptoms, cognitive impairment, ataxia and myelopathy were frequently observed while thromboembolic events and glomerulopathies were almost exclusively seen in adults. Brain atrophy, white matter lesions and myelopathy were frequently encountered. The majority of patients showed marked biochemical and clinical response to treatment with parenteral hydroxocobalamin combined with oral betaine, folate, carnitine and rarely methionine. The course was less favourable in late treated or untreated patients.

Conclusions: The late-onset cblC defect is a rare disease and unfortunately, diagnosis is often delayed. Raising awareness for this disorder can significantly improve patients' outcome and perspective by timely initiation of targeted treatment. Newborn screening (NBS) for the cblC defect might be of benefit especially for late-onset patients since treatment seems efficient when initiated before irreversible organ damage. In general, inborn errors of metabolisms should be considered in unexplained medical cases at any age, especially in patients with multisystemic disease. More specifically, total homocysteine in plasma and methylmalonic acid in urine/plasma should be measured in unexplained neurologic, psychiatric, renal, haematologic and thromboembolic disease.

No MeSH data available.


Related in: MedlinePlus

Frequency of clinical signs and symptoms in 55 patients with the late-onset cblC defect.
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Related In: Results  -  Collection

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Fig1: Frequency of clinical signs and symptoms in 55 patients with the late-onset cblC defect.

Mentions: Table 1 summarizes the information on gender, age and clinical signs at presentation, treatment and outcome in the published cases (not including the three new cases presented in this report). Descriptions of clinical signs and symptoms were extracted from reports on 55 symptomatic patients [Figure 1]. Overall, cognitive decline/impairment was the most frequent symptom, followed by neurological symptoms such as affections of the spinal cord myelin, ataxia and seizures. Haemolytic uraemic syndrome (HUS) and pulmonary arterial hypertension (PAH) were often associated. Macrocytosis or macrocytic anaemia were present in less than 20% of cases. Glomerulopathies as well as thromboembolic events were rarely observed.Table 1


Three new cases of late-onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy.

Huemer M, Scholl-Bürgi S, Hadaya K, Kern I, Beer R, Seppi K, Fowler B, Baumgartner MR, Karall D - Orphanet J Rare Dis (2014)

Frequency of clinical signs and symptoms in 55 patients with the late-onset cblC defect.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4255922&req=5

Fig1: Frequency of clinical signs and symptoms in 55 patients with the late-onset cblC defect.
Mentions: Table 1 summarizes the information on gender, age and clinical signs at presentation, treatment and outcome in the published cases (not including the three new cases presented in this report). Descriptions of clinical signs and symptoms were extracted from reports on 55 symptomatic patients [Figure 1]. Overall, cognitive decline/impairment was the most frequent symptom, followed by neurological symptoms such as affections of the spinal cord myelin, ataxia and seizures. Haemolytic uraemic syndrome (HUS) and pulmonary arterial hypertension (PAH) were often associated. Macrocytosis or macrocytic anaemia were present in less than 20% of cases. Glomerulopathies as well as thromboembolic events were rarely observed.Table 1

Bottom Line: Raising awareness for this disorder can significantly improve patients' outcome and perspective by timely initiation of targeted treatment.Newborn screening (NBS) for the cblC defect might be of benefit especially for late-onset patients since treatment seems efficient when initiated before irreversible organ damage.More specifically, total homocysteine in plasma and methylmalonic acid in urine/plasma should be measured in unexplained neurologic, psychiatric, renal, haematologic and thromboembolic disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolic Diseases and Children's Research Center, University Children's Hospital Zürich, Zürich, Switzerland. martina.huemer@kispi.uzh.ch.

ABSTRACT

Background: The cblC defect is a rare inborn error of intracellular cobalamin metabolism. Biochemical hallmarks are elevated homocysteine and low methionine in plasma accompanied by methylmalonic aciduria. Due to the heterogeneous clinical picture, patients with the late-onset form of the disease (onset >12 months) come to the attention of diverse medical specialists, e.g. paediatricians, neurologists, nephrologists, psychiatrists or haematologists. The report reviews the published clinical data and adds three new cases to raise awareness for this severe but often treatable disease.

Methods: The Pubmed and the Cochrane databases were searched for clinical reports on cblC patients and three unreported cases are presented to illustrate the clinical spectrum.

Results: Reports on 58 cases (30 females, 22 males, 6 = no information) and the three new cases underlined the clinical heterogeneity of the disease. Time between first symptoms and diagnosis ranged from three months to more than 20 years. Haemolytic uraemic syndrome and pulmonary hypertension were main presenting symptoms in preschool children. In older children/adolescents, psychiatric symptoms, cognitive impairment, ataxia and myelopathy were frequently observed while thromboembolic events and glomerulopathies were almost exclusively seen in adults. Brain atrophy, white matter lesions and myelopathy were frequently encountered. The majority of patients showed marked biochemical and clinical response to treatment with parenteral hydroxocobalamin combined with oral betaine, folate, carnitine and rarely methionine. The course was less favourable in late treated or untreated patients.

Conclusions: The late-onset cblC defect is a rare disease and unfortunately, diagnosis is often delayed. Raising awareness for this disorder can significantly improve patients' outcome and perspective by timely initiation of targeted treatment. Newborn screening (NBS) for the cblC defect might be of benefit especially for late-onset patients since treatment seems efficient when initiated before irreversible organ damage. In general, inborn errors of metabolisms should be considered in unexplained medical cases at any age, especially in patients with multisystemic disease. More specifically, total homocysteine in plasma and methylmalonic acid in urine/plasma should be measured in unexplained neurologic, psychiatric, renal, haematologic and thromboembolic disease.

No MeSH data available.


Related in: MedlinePlus