Adolescent/adult-onset homocysteine remethylation disorders characterized by gait disturbance with/without psychiatric symptoms and cognitive decline: a series of seven cases

Chang, Kai-Jie; Zhao, Zhe; Shen, Hongrui; Qi, Bing; Li, Nan; Guo, Xuan; Hu, Jing

doi:10.1007/s10072-020-04756-0

Cited by 14 publications

(21 citation statements)

References 31 publications

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“…As opposed to pediatric patients, the onset of the disease is often very insidious in adults, with psychiatric symptoms and slow cognitive decline, without the characteristic brain imaging anomalies from the very beginning. Mild psychiatric symptoms such as introversion and paranoia can be neglected for a long time, as shown by our case report and previous series describing patients with neuropsychiatric onset [ 11 ].…”

Section: Discussionmentioning

confidence: 68%

“…This notwithstanding, even among adult onset cases, there is a very variable clinical presentation associated to the very same pathogenic variants within members from the same family, as shown by the siblings described by Gold et al [ 14 ] (patient 30 Table 1 and sister with onset of symptoms at age 12), Powers et al [ 26 ] (patients 37 and 44 Table 1 ), and Boxer et al [ 27 ] (patient 41 Table 1 and sister with onset of symptoms at age 6). As in other monogenic disorders, the reason for this variability likely roots back to other environmental factors, including diet, and the rest of the genetic background acting as a phenotype modifier [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…About 90% of patients which have been reported in the medical literature had an early onset of the disease [ 9 ]. The late onset form is much rarer, with no more than 150 cases reported up to now [ 8 – 11 ]. The disease is thus considered to be mostly pediatric and there is a scarce knowledge of its presentation in adults.…”

Section: Introductionmentioning

confidence: 99%

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Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists

Kalantari

Brezzi

Bracciamà

et al. 2022

Orphanet J Rare Dis

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Background Methylmalonic aciduria and homocystinuria, CblC type (OMIM #277400) is the most common disorder of cobalamin intracellular metabolism, an autosomal recessive disease, whose biochemical hallmarks are hyperhomocysteinemia, methylmalonic aciduria and low plasma methionine. Despite being a well-recognized disease for pediatricians, there is scarce awareness of its adult presentation. A thorough analysis and discussion of cobalamin C defect presentation in adult patients has never been extensively performed. This article reviews the published data and adds a new case of the latest onset of symptoms ever described for the disease. Results We present the emblematic case of a 45-year-old male, describing the diagnostic odyssey he ventured through to get to the appropriate treatment and molecular diagnosis. Furthermore, available clinical, biochemical and molecular data from 22 reports on cases and case series were collected, resulting in 45 adult-onset CblC cases, including our own. We describe the onset of the disease in adulthood, encompassing neurological, psychiatric, renal, ophthalmic and thromboembolic symptoms. In all cases treatment with intramuscular hydroxycobalamin was effective in reversing symptoms. From a molecular point of view adult patients are usually compound heterozygous carriers of a truncating and a non-truncating variant in the MMACHC gene. Conclusion Adult onset CblC disease is a rare disorder whose diagnosis can be delayed due to poor awareness regarding its presenting insidious symptoms and biochemical hallmarks. To avoid misdiagnosis, we suggest that adult onset CblC deficiency is acknowledged as a separate entity from pediatric late onset cases, and that the disease is considered in the differential diagnosis in adult patients with atypical hemolytic uremic syndromes and/or slow unexplained decline in renal function and/or idiopathic neuropathies, spinal cord degenerations, ataxias and/or recurrent thrombosis and/or visual field defects, maculopathy and optic disc atrophy. Plasma homocysteine measurement should be the first line for differential diagnosis when the disease is suspected. To further aid diagnosis, it is important that genes belonging to the intracellular cobalamin pathway are included within gene panels routinely tested for atypical hemolytic uremic syndrome and chronic kidney disorders.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists

Kalantari

Brezzi

Bracciamà

et al. 2022

Orphanet J Rare Dis

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“…However, currently, more lateonset combined MMA with homocystinuria patients have been diagnosed. Some cases have been reported in adolescence or adulthood [15][16] .…”

Section: Discussionmentioning

confidence: 99%

Easily Misdiagnosed cblC Deficiency in Adolescents: the Clinical and Metabolic Studies

Chen

Dong

Liu

et al. 2022

Preprint

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Purpose: Adolescents are easily attacked by potential inherited metabolic disorders. cblC deficiency is the most common type of methylmalonic aciduria in China. The late-onset patients present with varied non-specific symptoms and usually being misdiagnosed. The purpose of this study is to investigate the clinical features of patients with adolescence-onset cblC deficiency and explore the prevention and control strategies. Methods: Fifty-seven patients (34 males and 23 females) with adolescence-onset cblC deficiency were admitted in our clinic from 2002 to September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome and genotypes-phenotypes correlation were examined.Results: The onset ages ranged from 10 to 25 years old (median age was 12 years). 16 cases (28.0%) presented with symptoms after infection or sports training. 46 patients (80.7%) had neuropsychiatric diseases. 14 patients (24.6%) displayed cardiovascular diseases. Five cases (8.9%) showed pulmonary hypertension. Renal damage was observed in seven cases (12.3%). 23 mutations were identified from the MMACHC gene of 57 patients. 37 patients demonstrated c.482G>A (64.9%) and 16 cases had c.609G>A (26.3%). Among 13 patients that exhibited spastic paraplegia as a main manifestation, 10 patients had c.482G>A (76.9%). Five patients presented with psychotic disorders and spastic paraplegia with c.482G>A. All patients improved after metabolic treatment with cobalamin, L-carnitine, and betaine. 30 school-aged patients returned to school. Two patients were married and had healthy babies.Conclusion: Patients with adolescence-onset cblC deficiency presented with varied neuropsychiatric symptoms or multiple organ damage. Metabolic studies and individualized treatment are keys to improve the outcome of the patients.

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“…Demyelinating polyneuropathy can also be prevalent in homocysteine remethylation disorders-the adult form of cobalamin C disease (CblC) and MTHFR (methylenetetrahydrofolate reductase) deficiency causing gait-ataxia and psychiatric symptoms, often together with a cognitive decline (which are better responsive to treatment than early onset forms [41]), as well as in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) [42].…”

Section: Chronic Demyelinating Neuropathiesmentioning

confidence: 99%

Update on Neuropathies in Inborn Errors of Metabolism

et al. 2021

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Neuropathies are relatively common in inborn errors of metabolism (IEMs); however, due to the early onset and severe, progressive course of many IEMs, they have not been very well researched yet. This article aims to review and compare neuropathies in inborn errors of metabolism, mostly with childhood and juvenile onset. Some of these diseases are treatable if diagnosed early and in many cases, the therapy can not only slow down disease progression, but can also reverse the changes already made by the condition.

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Adolescent/adult-onset homocysteine remethylation disorders characterized by gait disturbance with/without psychiatric symptoms and cognitive decline: a series of seven cases

Cited by 14 publications

References 31 publications

Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists

Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists

Easily Misdiagnosed cblC Deficiency in Adolescents: the Clinical and Metabolic Studies

Update on Neuropathies in Inborn Errors of Metabolism

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