Chenodeoxycholic acid (CDCA) treatment during pregnancy in women with cerebrotendinous xanthomatosis (CTX): Lessons learned from 19 pregnancies.

Purpose: Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder. Biallelic pathogenic variants in CYP27A1, encoding for sterol 27-hydroxylase, impair cholic acid (CA) and chenodeoxycholic acid (CDCA) synthesis and lead to accumulation of cholestanol and C bile alcohols. Treatment with CDCA decreases the accumulation of these harmful metabolites and slows disease progression.

Characterization of Postprandial Bile Acid Profiles and Glucose Metabolism in Cerebrotendinous Xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7α-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls.

Dilated fixed pupils and respiratory failure: a rare clinical course of Lambert-Eaton myasthenic syndrome.

Background: Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder and the clinical triad consists of proximal muscle weakness, autonomic symptoms and reduced tendon reflexes. Sluggish pupillary reflexes are common but dilated fixed pupils are rare.

Case Presentation: We report a patient with a rare clinical course of LEMS.

Newborn screening for Cerebrotendinous Xanthomatosis: A retrospective biomarker study using both flow-injection and UPLC-MS/MS analysis in 20,000 newborns.

Background And Aims: Cerebrotendinous Xanthomatosis (CTX) is a treatable disorder of bile acid synthesis caused by deficiency of 27-sterol hydroxylase -encoded by CYP27A1- leading to gastrointestinal and progressive neuropsychiatric symptoms. Biochemically, CTX is characterized by accumulation of the bile alcohol cholestanetetrol glucuronide (GlcA-tetrol) and the deficiency of tauro-chenodeoxycholic acid (t-CDCA) and tauro-trihydroxycholestanoic acid (t-THCA).

Materials And Methods: To ascertain the feasibility of CTX newborn screening (NBS) we performed a study with deidentified Dutch dried blood spots using reagents and equipment that is frequently used in NBS laboratories.

Child Neurology: Maternal Transmission of Congenital Myotonic Dystrophy Type 2: Case Report.

Congenital manifestations in Myotonic Dystrophy type 2 (DM2) point to anticipation and have only rarely been described. We report a three-generation family with genetically confirmed DM2. The youngest family member presented with unilateral congenital pes planovalgus and equinus.

Long-term MRI Findings in Patients With Cerebrotendinous Xanthomatosis Treated With Chenodeoxycholic Acid.

Objectives: To describe long-term follow-up brain MRI findings in patients with cerebrotendinous xanthomatosis (CTX) treated with chenodeoxycholic acid (CDCA).

Methods: Of a cohort of 79 Dutch patients with CTX, we retrospectively reviewed brain MRI findings of patients at diagnosis (before the start of treatment) and after long-term follow-up (7-27 years) in 12 patients. In addition, we report on 2 families with remarkable brain MRI findings.

Eye movement disorders in inborn errors of metabolism: A quantitative analysis of 37 patients.

Inborn errors of metabolism are genetic disorders that need to be recognized as early as possible because treatment may be available. In late-onset forms, core symptoms are movement disorders, psychiatric symptoms, and cognitive impairment. Eye movement disorders are considered to be frequent too, although specific knowledge is lacking.

[Awakening ptosis].

Background: A variable ptosis may point towards serious neurological disorders and is presented to general practitioners, ophthalmologists and neurologists.

Case Description: Two patients presented at the neurology outpatient clinic with a ptosis confined to awakening from sleep. There were no other neurological complaints and neurological examination was normal.

Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established.

Cerebrotendinous xanthomatosis without neurological involvement.

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement.

Cerebrotendinous xanthomatosis-associated diarrhea and response to chenodeoxycholic acid treatment.

Background: In patients with cerebrotendinous xanthomatosis (CTX), chronic diarrhea is one of the earliest and main symptoms of the disease. In the current study, we evaluated the characteristics of the diarrhea and its response to chenodeoxycholic acid (CDCA) therapy in a cohort of Dutch CTX patients.

Methods: We performed a retrospective review of medical records for 33 genetically confirmed CTX patients, and abstracted the characteristics of the diarrhea and the response to CDCA therapy (15 mg/kg/day up to 750 mg/day).

Five men with arresting and relapsing cerebral adrenoleukodystrophy.

Background: X-linked adrenoleukodystrophy (ALD) is the most common genetic peroxisomal disorder with an estimated prevalence of 1:15,000. Approximately two-thirds of males with ALD manifest the inflammatory demyelinating cerebral phenotype (cALD) at some disease stage, in which focal, inflammatory lesions progress over months to years. Hematopoietic stem-cell transplantation can permanently halt cALD progression, but it is only effective if initiated early.

The safety and effectiveness of chenodeoxycholic acid treatment in patients with cerebrotendinous xanthomatosis: two retrospective cohort studies.

Objective: To evaluate the safety and effectiveness of chenodeoxycholic acid (CDCA) treatment in patients with cerebrotendinous xanthomatosis (CTX).

Methods: Two retrospective cohort studies were conducted in CTX patients who underwent CDCA treatment: one in the Netherlands (NL; CDCA-STUK-15-001) and one in Italy (IT; CDCA-STRCH-CR-14-001). Eligible patients were aged 2-75 years, had been diagnosed with CTX, and were treated with CDCA orally for ≥1 year.

Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients.

In this retrospective study, we conducted a clinico-genetic analysis of patients with autosomal recessive limb-girdle muscular dystrophy (LGMD) and Miyoshi muscular dystrophy (MMD). Patients were identified at the tertiary referral centre for DNA diagnosis in the Netherlands and included if they carried two mutations in CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TRIM32, FKRP or ANO5 gene. DNA was screened by direct sequencing and multiplex ligand-dependent probe amplification (MLPA) analysis.

Leigh syndrome caused by mutations in is associated with a better prognosis.

Objectives: Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is required for the initiation of translation and elongation of mitochondrial protein synthesis Pathogenic variants in have been associated with Leigh syndrome (LS) and mitochondrial multiple respiratory chain deficiencies. We sought to elucidate the spectrum of clinical, neuroradiological and molecular genetic findings of patients with bi-allelic pathogenic variants in .

Methods: Retrospective cohort study combining new cases and previously published cases.

Long-term treatment effect in cerebrotendinous xanthomatosis depends on age at treatment start.

Objective: To evaluate the effect of chenodeoxycholic acid treatment on disease progression in cerebrotendinous xanthomatosis (CTX).

Methods: In this retrospective cohort study, we report the clinical long-term follow-up characteristics of 56 Dutch patients with CTX. Age at diagnosis was correlated with clinical characteristics and with the course of modified Rankin Scale (mRS) and Expanded Disability Status Scale (EDSS) scores at follow-up.

Mycoplasma Pneumoniae and Antibodies against Galactocerebroside in a 9-Year-Old Boy with Encephalitis.

We report the case of a 9 year-old boy, presenting with an acute encephalitis with cerebrospinal fluid pleiocytosis. MRI showed T2/FLAIR (fluid attenuated inversion recovery) hyperintense signals of basal ganglia and cortex, EEG (electro encephalogram) showed diffuse slowing with epileptic discharges. A repetitively elevated IgM/IgG serologic response against was observed with polymerase chain reaction in serum and cerebrospinal fluid remaining negative.

A recurrent de novo DYNC1H1 tail domain mutation causes spinal muscular atrophy with lower extremity predominance, learning difficulties and mild brain abnormality.

We describe four unrelated patients with the same de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene. We found a high phenotype-genotype correlation with all four patients having early childhood-onset predominant lower limb muscle weakness and wasting which was slowly progressing and later-onset mild upper extremities proximal weakness.

Movement disorders in cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is an inborn error of cholesterol and bile acid metabolism, leading to neuropsychiatric and systemic manifestations. Movement disorders have rarely been reported in CTX, while a detailed appreciation of the full phenotypic spectrum is required in order to prevent underdiagnosis of this disease. This review focuses on the frequency of more unusual, non-ataxia and non-spasticity movement disorders reported in CTX.

Qualitative and Quantitative Aspects of Pain in Patients With Myotonic Dystrophy Type 2.

Unlabelled: Pain is a common but often ignored symptom in patients with myotonic dystrophy type 2 (DM2). In this explorative study, we assessed qualitative and quantitative aspects of pain in DM2 using 4 questionnaires and quantitative sensory testing. A disease control group (fibromyalgia [FMS]) as well as healthy controls were used to compare the results, because pain in DM2 shows many clinical similarities to pain in FMS.

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study.

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.

Extremely Painful Multifocal Acquired Predominant Axonal Sensorimotor Neuropathy of the Upper Limb.

The differential diagnosis of upper extremity mononeuritis multiplex includes neuralgic amyotrophy, vasculitic neuropathy, and Lewis-Sumner syndrome. We describe 3 patients initially suspected of neuralgic amyotrophy, who had an extremely painful, protracted, progressive disease course, not fitting one of these established diagnoses. Nerve ultrasonography showed focal caliber changes of the roots, plexus, and limb nerves.