Lesch‐nyhan variant: Dystonia, ataxia, near‐normal intelligence, and no self‐mutilation

Adler, Charles H.; Wrabetz, Lawrence

doi:10.1002/mds.870110519

Cited by 9 publications

(3 citation statements)

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“…There also are rare reports of patients with clinical features not found in our patients. Two cases from the literature were reported to have a spinocerebellar syndrome (Kelley et al , 1969 ) and another was reported to have ataxia with dystonia (Adler and Wrabetz, 1996 ). However, the first two cases were re-evaluated by others who described an extrapyramidal syndrome rather than ataxia (Nyhan, 1978 ).…”

Section: Discussionmentioning

confidence: 99%

Attenuated variants of Lesch-Nyhan disease

Jinnah

Ceballos-Picot

Torres

et al. 2010

Brain

150

116

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Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency.

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Section: Discussionmentioning

confidence: 99%

Attenuated variants of Lesch-Nyhan disease

Jinnah

Ceballos-Picot

Torres

et al. 2010

Brain

150

116

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“…The 76 studies included in this review [ 16 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 ] were published between 1964 [ 39 ] and 2022 [ 80 ] and were conducted in various countries (Table S2). Of these, 30 were case reports, and 46 were case series.…”

Section: Resultsmentioning

confidence: 99%

Catching the Culprit: How Chorea May Signal an Inborn Error of Metabolism

Ortigoza-Escobar

2023

TOHM

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Background: Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this context, comprehensive descriptions of movement disorders are limited and primarily derived from single cases or small patient series, highlighting the need for increased awareness and additional research in this field. Methods: A systematic review was conducted using the MEDLINE database and GeneReviews. The search included studies on inborn errors of metabolism associated with chorea, athetosis, or ballismus. The review adhered to PRISMA guidelines. Results: The systematic review analyzed 76 studies out of 2350 records, encompassing the period from 1964 to 2022. Chorea was observed in 90.1% of the 173 patients, followed by athetosis in 5.7%. Various inborn errors of metabolism showed an association with chorea, with trace elements and metals being the most frequent. Cognitive and developmental abnormalities were common in the cohort. Frequent neurological features included seizures, dysarthria, and optic atrophy, whereas non-neurological features included, among others, facial dysmorphia and failure to thrive. Neuroimaging and biochemical testing played crucial roles in aiding diagnosis, revealing abnormal findings in 34.1% and 47.9% of patients, respectively. However, symptomatic treatment efficacy for movement disorders was limited. Discussion: This study emphasizes the complexities of chorea in inborn errors of metabolism. A systematic approach with red flags, biochemical testing, and neuroimaging is required for diagnosis. Collaboration between neurologists, geneticists, and metabolic specialists is crucial for improving early detection and individualized treatment. Utilizing genetic testing technologies and potential therapeutic avenues can aid in the improvement of patient outcomes.

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“…• Huntington's disease [14,95] • C9orf72 expansion mutation (frontotemporal dementia, motor neuron disease and movement disorders, probably frequent phenocopy of HD [43]) • Spinocerebellar ataxia 17 (corresponds to Huntington's-disease-like-4; HDL4 [95]) • Spinocerebellar ataxia types 3, 2, 1 and 7 [78] • Spinocerebellar ataxia type 8 [95] • Spinocerebellar ataxia type 12 (mainly India [48,95] [13,14] Other rare inherited disease entities • Huntington's disease-like 1 and 3, only described in individual families [14] • HDL1 with prion protein (PrP) gene mutations (PRNP) and rapid progression [14,95] • HDL3, a family [47] • RNF216 mutation (autosomal recessive, leukoencephalopathic lesions and possibly Serum gonadotropin ↓ [93]) • ANO3 mutations [52] • FRRS1L mutations (Saudi Arabia; also epilepsy [95]) • Primary Familial Brain Calcification (formerly "Fahr's disease", cMRI/CCT helpful (SLC20A2-,PDGFB, PDGFRB or XPR1 gene [95]) • POLG gene mutations (dystonia, myoclonus, discrete chorea [101]) • Leigh's disease [63] • SETX mutation (with motor neuron disease [94]) • Laurence-Moon-Biedl-Bardet syndrome [65] • Friedreich ataxia [41] • NBIA "neurodegeneration with brain iron accumulation" (umbrella term for e. dystrophy (PLA2G6), C19orf12, C2orf37, FA2H, ATP13A2, COASY and DCAF17 mutations-more likely no chorea)) with iron deposits in the basal ganglia as a typical MRI finding [3,14,82,95,103,113]) • Wilson's disease [14,95] • TAR DNA binding protein variation (TARDBP; with frontotemporal dementia [51]) • Lesch-Nyhan syndrome; X-linked [1,14] • Niemann-Pick type C …”

Section: Hereditary Disease Entities Presenting With Chorea or Featur...mentioning

confidence: 99%

Differential diagnosis of chorea (guidelines of the German Neurological Society)

Saft,

Burgunder,

Dose

et al. 2023

Neurol. Res. Pract.

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Introduction Choreiform movement disorders are characterized by involuntary, rapid, irregular, and unpredictable movements of the limbs, face, neck, and trunk. These movements often initially go unnoticed by the affected individuals and may blend together with seemingly intended, random motions. Choreiform movements can occur both at rest and during voluntary movements. They typically increase in intensity with stress and physical activity and essentially cease during deep sleep stages. In particularly in advanced stages of Huntington disease (HD), choreiform hyperkinesia occurs alongside with dystonic postures of the limbs or trunk before they typically decrease in intensity. Summary or definition of the topic The differential diagnosis of HD can be complex. Here, the authors aim to provide guidance for the diagnostic process. This guidance was prepared for the German Neurological Society (DGN) for German-speaking countries. Recommendations Hereditary (inherited) and non-hereditary (non-inherited) forms of chorea can be distinguished. Therefore, the family history is crucial. However, even in conditions with autosomal-dominant transmission such as HD, unremarkable family histories do not necessarily rule out a hereditary form (e.g., in cases of early deceased or unknown parents, uncertainties in familial relationships, as well as in offspring of parents with CAG repeats in the expandable range (27–35 CAG repeats) which may display expansions into the pathogenic range). Conclusions The differential diagnosis of chorea can be challenging. This guidance prepared for the German Neurological Society (DGN) reflects the state of the art as of 2023.

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Lesch‐nyhan variant: Dystonia, ataxia, near‐normal intelligence, and no self‐mutilation

Cited by 9 publications

References 4 publications

Attenuated variants of Lesch-Nyhan disease

Attenuated variants of Lesch-Nyhan disease

Catching the Culprit: How Chorea May Signal an Inborn Error of Metabolism

Differential diagnosis of chorea (guidelines of the German Neurological Society)

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