Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment

Teive, Hélio Afonso Ghizoni; Camargo, Carlos Henrique Ferreira; Pereira, Eduardo Rafael; Coutinho, Léo; Munhoz, Renato P.

doi:10.1007/s10048-022-00688-3

Cited by 3 publications

(6 citation statements)

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“…We summarize the known morbidity spectrum of MSMO1 deficiency in Table 2. Spasticity is not an uncommon feature among various neurometabolic conditions even in the absence of structural brain anomalies (Teive et al ., 2022). Of note, hereditary spastic paraplegia type 5 is characterized by the accumulation of 27-hydroxycholesterol in plasma and cerebrospinal fluid and treatment with statins improves the symptoms (Mignarri et al ., 2015).…”

Section: Discussionmentioning

confidence: 99%

MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly

Tkemaladze

Bratland

Bregvadze

et al. 2023

Clinical Dysmorphology

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MSMO1 deficiency (OMIM #616834) is an ultrarare autosomal recessive disorder of distal cholesterol metabolism with only five cases reported to date. The disorder is caused by missense variants in the MSMO1 gene encoding methylsterol monooxygenase 1, leading to the accumulation of methylsterols. Clinically, MSMO1 deficiency is characterized by growth and developmental delay, often in association with congenital cataracts, microcephaly, psoriasiform dermatitis and immune dysfunction. Treatment with oral and topical cholesterol supplements and statins was reported to improve the biochemical, immunological, and cutaneous findings, supporting a potential treatment following the precision diagnosis of MSMO1 deficiency. We describe two siblings from a consanguineous family presenting with novel clinical features of polydactyly, alopecia and spasticity. Whole-exome sequencing revealed a novel, homozygous c.548A > C, p.(Glu183Ala) variant. Based on previously published treatment algorithms, we initiated a modified dosage regime with systemic cholesterol supplementation, statins and bile acid along with topical application of a cholesterol/statin formulation. This resulted in a marked improvement of psoriasiform dermatitis and some hair growth.

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Section: Discussionmentioning

confidence: 99%

MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly

Tkemaladze

Bratland

Bregvadze

et al. 2023

Clinical Dysmorphology

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“…The clinical picture in early childhood is characterized by tachypnea, hypotonia, developmental delay, seizures, and cutaneous features, such as skin rash with exfoliation and alopecia, while later onsets (late infancy, juvenile age, or even adulthood) occur due to partial BD with similar but usually milder features, which may however greatly differ from case to case; thus, symptoms resembling complex forms of HSP (hereditary spastic paraplegia) have been described among cases with the delayed onset form of BD, in older children, adolescents, or even adults. Unfortunately, the age of diagnosis seems to be inversely correlated with the reversibility of BD symptoms [ 32 , 33 , 34 ].…”

Section: Defects In Biotin Homeostasis/recycling: Treatment With Biotinmentioning

confidence: 99%

“…Mutational analysis : BD may be confirmed by means of mutational analysis of the biotinidase gene, which is located on chromosome 3p25 [ 30 , 34 ]. Certain enzyme mutants have been identified in affected newborns through national screening programs [ 39 ], or via independent studies [ 40 ], while more than 240 mutations have already been identified [ 34 ].…”

Section: Defects In Biotin Homeostasis/recycling: Treatment With Biotinmentioning

confidence: 99%

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Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives

Karachaliou,

Livaniou

2024

IJMS

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Biotin (vitamin B7, or vitamin H) is a water-soluble B-vitamin that functions as a cofactor for carboxylases, i.e., enzymes involved in the cellular metabolism of fatty acids and amino acids and in gluconeogenesis; moreover, as reported, biotin may be involved in gene regulation. Biotin is not synthesized by human cells, but it is found in food and is also produced by intestinal bacteria. Biotin status/homeostasis in human individuals depends on several factors, including efficiency/deficiency of the enzymes involved in biotin recycling within the human organism (biotinidase, holocarboxylase synthetase), and/or effectiveness of intestinal uptake, which is mainly accomplished through the sodium-dependent multivitamin transporter. In the last years, administration of biotin at high/“pharmacological” doses has been proposed to treat specific defects/deficiencies and human disorders, exhibiting mainly neurological and/or dermatological symptoms and including biotinidase deficiency, holocarboxylase synthetase deficiency, and biotin–thiamine-responsive basal ganglia disease. On the other hand, according to warnings of the Food and Drug Administration, USA, high biotin levels can affect clinical biotin-(strept)avidin assays and thus lead to false results during quantification of critical biomarkers. In this review article, recent findings/advancements that may offer new insight in the abovementioned research fields concerning biotin will be presented and briefly discussed.

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“…Congenital diarrhea and Alagille syndrome are important differential diagnoses in childhood onset, as well as other causes of neonatal jaundice. In adult patients, differential diagnosis is made with other causes of progressive neurologic disease, such as HSP, hereditary cerebellar ataxias, multiple sclerosis, leukodystrophies, mitochondrial disease, histiocytosis, and other causes of acquired ataxia, and in these cases tendon xanthomas and cataracts are among the most important clues for CTX (53).…”

Section: Figurementioning

confidence: 99%

Cerebrotendinous Xanthomatosis: A practice review of pathophysiology, diagnosis, and treatment

et al. 2022

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Cerebrotendinous Xanthomatosis represents a rare and underdiagnosed inherited neurometabolic disorder due to homozygous or compound heterozygous variants involving the CYP27A1 gene. This bile acid metabolism disorder represents a key potentially treatable neurogenetic condition due to the wide spectrum of neurological presentations in which it most commonly occurs. Cerebellar ataxia, peripheral neuropathy, spastic paraparesis, epilepsy, parkinsonism, cognitive decline, intellectual disability, and neuropsychiatric disturbances represent some of the most common neurological signs observed in this condition. Despite representing key features to increase diagnostic index suspicion, multisystemic involvement does not represent an obligatory feature and can also be under evaluated during diagnostic work-up. Chenodeoxycholic acid represents a well-known successful therapy for this inherited metabolic disease, however its unavailability in several contexts, high costs and common use in patients at late stages of disease course limit more favorable neurological outcomes for most individuals. This review article aims to discuss and highlight the most recent and updated knowledge regarding clinical, pathophysiological, neuroimaging, genetic and therapeutic aspects related to Cerebrotendinous Xanthomatosis.

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Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment

Cited by 3 publications

References 71 publications

MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly

MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly

Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives

Cerebrotendinous Xanthomatosis: A practice review of pathophysiology, diagnosis, and treatment

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