L-2 hydroxyglutaric aciduria: report of a Mexican-Mayan patient with the mutation c.569C>T and response to vitamin supplements and levocarnitine.

Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.

Latencia diagnóstica y percepción de síntomas prodrómicos en pacientes con enfermedad de Parkinson en Yucatán / Diagnostic latency and perception of prodromal symptoms in patients with Parkinson's disease in Yucatán

Resumen Objetivo: Determinar la latencia diagnóstica en la enfermedad de Parkinson (EP), así como su relación con variables clínicas y demográficas. Determinar la percepción de síntomas no motores: disfunción olfatoria, trastorno conductual del sueño MOR, depresión y estreñimiento, previos al diagnóstico de EP. Materiales y métodos: Estudio transversal realizado en Yucatán, México en sujetos con EP. Se analizó la asociación entre la latencia diagnóstica con variables clínicas y demográficas usando las pruebas estadísticas no paramétricas: U de Mann Whitney y Kruskal-Wallis. Resultados: Se incluyeron un total de 60 sujetos con una edad promedio de 66.7 años. El tiempo promedio transcurrido desde el inicio del primer síntoma motor hasta el diagnóstico fue de 20.8 meses. El tener antecedentes familiares de EP se asoció significativamente (p=0.031) con una latencia diagnóstica más prolongada en comparación con aquellos pacientes que no refirieron familiares con EP. En cualquier momento antes del diagnóstico de EP: el 36.6% de los pacientes percibieron estreñimiento, 15% depresión, 13.3% trastorno conductual del sueño MOR y 11.6% disfunción olfatoria, 51.7% no refirió ninguno. Conclusiones: La latencia diagnóstica promedio de un grupo de 60 pacientes con EP diagnosticados en Yucatán fue de 20.8 meses. La latencia diagnóstica no se asoció significativamente con el tipo de servicio médico de neurología que realizó en diagnóstico de EP (público o privado), ni con otras variables clínicas ni demográficas además del antecedente familiar de EP.

Abstract Objective: To determine the diagnostic latency in Parkinson's disease (PD), and its relationship with clinical and demographic variables. To determine the perception of non-motor symptoms: olfactory dysfunction, REM sleep behavior disorder, depression, and constipation, prior to the diagnosis of PD. Materials and methods: Cross-sectional study conducted in Yucatan, Mexico in subjects with PD. The association between diagnostic latency with clinical and demographic variables was analyzed using the non-parametric statistical tests: Mann Whitney U and Kruskal-Wallis. Results: A total of 60 subjects with a mean age of 66.7 years were included. The average time elapsed from the onset of the first sympoton to diagnosis was 20.8 months. A family history of PD was significantly associated (p=0.031) with a longer diagnostic latency compared to those patients who did not have relatives with PD. Before the diagnosis of PD: 36.6% of the patients perceived constipation, 15% depression, 13.3% REM sleep behavior disorder and 11.6% olfactory dysfunction, 51.7% did not report any. Conclusions: The mean diagnostic latency of a group of 60 patients with PD diagnosed in Yucatan was 20.8 months. Diagnostic latency was not significantly associated with the type of neurological medical service that performed the diagnosis (public or private), or with other clinical or demographic variables in addition to a family history of PD.