Analysis of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with Hereditary hyperferinemia cataract syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical data and genetic characteristics of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with Hereditary hyperferritinemia cataract syndrome (HHCS).@*METHODS@#A child who was admitted to the PICU of the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the child was collected. Genetic testing was carried out for the child, and the result was analyzed in the light of literature review to explore the clinical and genetic characteristics to facilitate early identification.@*RESULTS@#The patient, a 3-year-old male, had mainly presented with visual impairment, progressive cognitive and motor regression, and epilepsy. Cranial magnetic resonance imaging revealed deepened sulci in bilateral cerebral hemispheres, and delayed myelination. The activity of palmitoyl protein thioesterase was low (8.4 nmol/g/min, reference range: 132.2 ~ 301.4 nmol/g/min), whilst serum ferritin was increased (2417.70 ng/mL, reference range: 30 ~ 400 ng/ml). Fundoscopy has revealed retinal pigment degeneration. Whole exome sequencing revealed that he has harbored c.280A>C and c.124-124+3delG compound heterozygous variants of the PPT1 gene, which were respectively inherited from his father and mother. Neither variant has been reported previously. The child has also harbored a heterozygous c.-160A>G variant of the FTL gene, which was inherited from his father. Based on the clinical phenotype and results of genetic testing, the child was diagnosed as CLN1 and HHCS.@*CONCLUSION@#The compound heterozygous variants of the PPT1 gene probably underlay the disorders in this child. For children with CLN1 and rapidly progressing visual impairment, ophthalmological examination should be recommended, and detailed family history should be taken For those suspected for HHCS, genetic testing should be performed to confirm the diagnosis.

Lipofuscinose ceróide neuronal: achados clínicos e neurorradiológicos / Neuronal ceroid lipofuscinosis: clinical and neuroradiological findings

Lipofuscinose ceróide neuronal (LCN) constitui um grupo de doenças neurodegenerativas caracterizadas pelo depósito anormal de uma substância autofluorescente de lipopigmentos, que lembra ceróide e lipofuscina, dentro dos lisossomos dos neurônios e outros tipos de células. Os principais subtipos fenotípicos, baseando-se na idade de início, curso clínico e morfologia ultraestrutural, são classificados em formas infantil, infantil tardia, juvenil e adulta. Seis genes associados a lipofuscinose ceróide foram identificados e aproximadamente 150 mutações também são descritas. Relatamos sete pacientes com LCN baseados na história clínica, achados neurorradiológicos e patológicos avaliados na Rede Sarah de Hospitais de Reabilitação - Fortaleza - Ceará - Brasil. Cinco casos foram confirmados com biópsia de pele, sendo dois casos irmãos de pacientes confirmados. O diagnóstico precoce de LCN, uma doença com herança autossômica recessiva, é mandatório para aconselhamento genético e prevenção de outros casos na família. Os achados de imagem podem contribuir no diagnóstico diferencial.

The neuronal ceroid lipofuscinoses (NCL) are a group of neurodegenerative disorders, characterized by abnormal storage of an autofluorescent substance of lipopigments, resembling ceroid and lipofuscin, within lysosomes of neurons and other types of cells. The main phenotypic subtypes have been established on the basis of age of onset, clinical course, and ultra structural morphology, and classified as infantile, late infantile, juvenile and adult forms. Six genes have been associated with human NCL and approximately 150 mutations have been described. The aim of this study is to report the clinical, neuroradiological, and morphological characteristics of seven patients evaluated at Sarah Network of Hospitals for Reabilitation - Fortaleza - Ceará - Brazil. Five cases were histopathologically confirmed with skin biopsy and two were siblings of confirmed patients. An early diagnosis of NCL, an autosomal recessive disease, is mandatory for genetic counseling and to avoid further cases in the family. Imaging findings can contribute to the differential diagnosis.

Neuronal ceroid lipofuscinoses: a clinical and morphological study of 17 patients from Southern Brazil

The neuronal ceroid lipofuscinoses (NCL) are a group of inherited progressive neurodegenerative disorders with presentation from infancy to adulthood. Three main childhood forms can be established on the basis of age of onset, clinical course, and ultrastructural morphology: infantile (INCL), late infantile (LINCL), and juvenile (JNCL). Several variant subtypes have been described. Genetic and biochemical analysis are helping to better understand, diagnose and classify these disorders. We report on clinical, neurophysiological, neuroradiological, and morphological data from 17 patients with different forms (infantile, late infantile, and juvenile ) of neuronal ceroid lipofuscinoses (NCL) evaluated at Hospital de Clínicas de Porto Alegre, Southern Brazil, during 6 years (1992-1997). Seven cases were infantile; 5 were late infantile; and 5 were juvenile NCL. Gender ratio was male:female, 11:6. Age at presentation varied from 2-24 months for INCL; 2,5 to 5 years for LINCL ; and 4-10 years for the JNCL cases. Seizures (6 patients) and psychomotor retardation (1 patient) were the initial symptoms in the INCL group. All the patients in the group of LINCL had the usual findings. JNCL patients manifested different initial symptoms, although tending to follow a similar clinical picture within familial cases. Epidemiological data on the prevalence of NCLs in Brazil are not available, we expect this series of cases to contribute to further research in our population

Lipofuscinosis ceroide neuronal: estudio neurofisiológico y morfológico en un paciente / Neuronal ceroid lipofuscinosis: neurophysiological and morphological study of a patient

Se realiza revisión de la lipofuscinosis ceroide neuronal (LCN) como patología. Se presenta el caso de un escolar de 9 años de edad portadora de una LCN variedad Spielmeyer-Vogt. La misma fue corroborada por las investigaciones neurofisiológicas realizadas que incluían retinograma, potenciales visuales evocados y electroencefalograma. Se realizó biopsia conjuntival y estudio ultraestructural que demuestra las alteraciones lisosomales