Dementia, diarrhea, desquamating shellac-like dermatitis revealing late-onset cobalamin C deficiency

Gilson, Robert Christopher; Wallis, Luke; Yeh, Jenny

doi:10.1016/j.jdcr.2017.09.016

Cited by 6 publications

(6 citation statements)

References 6 publications

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“…It impairs conversion of dietary vitamin B12 and causes deficient synthesis of methylcobalamin and adenosylcobalamin. Diagnostic laboratory findings of cblC disease include elevated levels of methylmalonic acid in the urine, homocysteine in the blood (2)(3)(4)(5)(6), and serum propionylcarnitine (C3). Moreover, the ratios of C3-to-acetylcarnitine (C2) are remarkably elevated (6).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the ratios of C3-to-acetylcarnitine (C2) are remarkably elevated (6). Depending on the onset time of disease, the cblC disease can be divided into two types, early-onset type in the infancy period (2) and late-onset type in adolescents or adults (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…The late-onset cblC disease is characterized by involvement of both the central nervous system and peripheral nerve system. The patients showed commonly cognitive and psychiatric disturbances (2,3,(5)(6)(7)(8), epilepsy (3)(4)(5)(6)(7)(8)(9), spastic paraplegia (3,7,8,10,11), with optic atrophy (3,12). Some patients showed typical subacute combined degeneration (7,13).…”

Section: Introductionmentioning

confidence: 99%

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Peripheral Nervous System Involvement in Late-Onset Cobalamin C Disease?

et al. 2020

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Background: Cobalamin C (cblC) has a fundamental role in both central and peripheral nervous system function at any age. Neurologic manifestations may be the earliest and often the only manifestation of hereditary or acquired cblC defect. Peripheral neuropathy remains a classical but underdiagnosed complication of cblC defect, especially in late-onset cblC disease caused by mutations in the methylmalonic aciduria type C and homocysteinemia (MMACHC) gene. So the clinical, electrophysiological, and pathological characteristics of late-onset cblC disease are not well-known.Methods: A retrospective study of patients with late-onset cblC disease was conducted at our hospital on a 3-year period. The neuropathy was confirmed by the nerve conduction study. Sural biopsies were performed in 2 patients.Results: Eight patients were identified, with a mean onset age of 16.25 ± 6.07 years. All patients had methylmalonic aciduria, homocysteinemia, compound heterozygous MMACHC gene mutations were detected in all patients, and 7/8 patients with c.482G>A mutation. One patient concomitant with homozygote c.665C>T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. All patients showed limb weakness and cognitive impairment. Five patients had possible sensorimotor axonal polyneuropathy predominantly in the distal lower limbs. Sural biopsies showed loss of myelinated and unmyelinated fibers. Electro microscopy revealed crystalline-like inclusions bodies in Schwann cells and axonal degeneration.Conclusion: Late-onset cblC disease had possible heterogeneous group of distal axonal neuropathy. c.482G>A mutation is a hot spot mutation in late-onset cblC disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Peripheral Nervous System Involvement in Late-Onset Cobalamin C Disease?

et al. 2020

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“…These mutations disrupt cobalamin metabolism, leading to the accumulation of toxic levels of metabolites, homocysteine and methylmalonic acid, which cause oxidative injury. While the central and peripheral nervous system are commonly affected, cblC deficiency can also involve more organs and tissues, including the kidneys ( 9 ), lung ( 10 ), micrangium ( 11 ), retina ( 12 ), and skin ( 6 ). Early-onset cblC deficiency, with an age of onset <12 months, is more prevalent and typically manifests with feeding difficulties, somnolence, developmental delays, seizures, muscular hypotonia, hydrocephalus, and microcephaly ( 1 , 4 , 8 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…cblC deficiency is associated with systemic involvement and complex clinical manifestations, including progressive encephalopathy, subacute combined degeneration of the spinal cord, maculopathy, anemia, thromboembolic complications, pulmonary arterial hypertension, and kidney injury ( 4 , 5 ). Skin manifestations, although rare, are often overlooked ( 6 ). Brain magnetic resonance imaging (MRI) findings commonly include hydrocephalus, progressive white matter abnormalities, and atypical lesions in the basal ganglia and cerebellum ( 4 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Case report: Desquamating dermatitis, bilateral cerebellar lesions in a late-onset methylmalonic acidemia patient

Chen,

Tang,

Zhang

et al. 2023

Front. Neurol.

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IntroductionCobalamin C (cblC) deficiency is a rare hereditary disorder affecting intracellular cobalamin metabolism, primarily caused by mutations in MMACHC. This condition is characterized by combined methylmalonic acidemia and hyperhomocysteinemia, displaying a wide range of clinical manifestations involving multiple organs. Owing to its uncommon occurrence and diverse clinical phenotypes, diagnosing cblC deficiency is challenging and often leads to delayed or missed diagnoses.Case descriptionIn this report, we present a case of late-onset cblC deficiency with brown desquamating dermatitis on the buttocks. Magnetic resonance imaging (MRI) of the brain revealed bilateral cerebellar abnormalities. The suspicion of an inherited metabolic disorder was raised by abnormal serum amino acid and acylcarnitine levels, along with increased urine methylmalonic acid and serum homocysteine levels. Whole-exome sequencing helped identify a homozygous variant (c.482G>A) in MMACHC, confirming the diagnosis of cblC deficiency. However, despite receiving treatment with hydroxocobalamin and betaine, the patient did not experience clinical improvement, which may be attributed to the delayed diagnosis as indicated by the declining homocysteine and methylmalonic acid levels.ConclusionCollectively, we emphasize the significance of recognizing the skin lesions and observing serial MRI changes in patients with cblC deficiency. Our case underscores the importance of early diagnosis and timely therapeutic intervention for this severe yet frequently manageable condition.

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