Algunos desafíos en mucopolisacaridosis tipo I / A few challenges in mucopolysaccharidosis type I

Se describen como desafíos actuales en mucopolisacaridosis I la necesidad de una clasificación adecuada, vinculándola a las indicaciones terapéuticas; el diagnóstico temprano desde la pesquisa neonatal, sus ventajas y dificultades hasta la sospecha clínica de las formas grave y atenuada; el cuidado de la patología espinal y oftalmológica, desde el diagnóstico, el seguimiento y el tratamiento; las reacciones alérgicas por terapia de reemplazo enzimático, su diagnóstico y tratamiento. Por último, la transición hacia el cuidado adulto

Here we describe the current challenges of mucopolysaccharidosis type I: the need for an adequate classification, establishing its relationship to therapeutic indications; an early diagnosis, from neonatal screening, its advantages and barriers, to clinical suspicion of severe and attenuated forms; spinal and eye disease care, from diagnosis to follow-up and treatment; allergic reactions caused by enzyme replacement therapy, their diagnosis and treatment. And lastly, transition to adult care

Nuevas recomendaciones para el cuidado de los pacientes con mucopolisacaridosis tipo I / New recommendations for the care of patients with mucopolysaccharidosis type I

Dados los avances sobre mucopolisacaridosis Icon posterioridad al consenso publicado en la Argentina por un grupo de expertos en 2008, se revisan recomendaciones respecto a estudios genéticos, seguimiento cardiológico, cuidado de la vía aérea, alertas sobre aspectos auditivos, de la patología espinal y neurológica. Se hace revisión de la terapéutica actual y se enfatiza en la necesidad de un diagnóstico y tratamiento precoces, así como de un seguimiento interdisciplinario

Considering the advances made on mucopolysaccharidosis type I after the consensus study published by a group of experts in Argentina in 2008, recommendations about genetic testing, cardiological follow-up, airway care, hearing impairment detection, spinal and neurological conditions, as well as current treatments, were reviewed. Emphasis was placed on the need for early diagnosis and treatment, as well as an interdisciplinary follow-up

Asociación de melanocitosis dérmica con enfermedades lisosomales / Association of dermal melanocytosis with lysosomal storage diseases

Introducción: la melanocitosis dérmica incluye un espectro de lesiones de piel que abarca la mancha mongólica, entre otras lesiones. Las enfermedades lisosomales son afecciones de base genética que se caracterizan por la acumulación de metabolitos insolubles parciamente degradados en los compartimentos lisosomales, debido a una determinada deficiencia enzimática. Las deficiencias de b-galactosidasa y de a-L-iduronidasa provocan la gangliosidosis GM1 y la mucopolisacaridosis tipo I respectivamente, ambas presentando similitudes en su presentación clínica. La asociación de la melanocitosis dérmica con las enfermedades lisosomales es poco común y mal entendida. Objetivo: reportar dos pacientes con esta rara asociación. Casos clínicos: dos varones de 3 y 9 meses sin antecedentes prenatales ni perinatales a destacar y antecedentes de infecciones respiratorias reiteradas. Se presentaron con retraso del desarrollo, hipotonía central y trastorno deglutorio. Al examen se constató hepatomegalia, fascies tosca y melanosis dérmica extensa. Los estudios permitieron diagnosticar al paciente de 3 meses mucopolisacaridosis Tipo I y al de 9 meses gangliosidosis GM1. Discusión: no se conoce exactamente la causa de esta asociación. Se plantea que sería el resultado de la acumulación de gangliósidos y heparán sulfato que estimularían al receptor del factor de crecimiento neuronal de tipo tirosinquinasa, deteniendo la migración de los melanocitos en la dermis. Por lo tanto la melanosis dérmica aberrante, en el contexto clínico adecuado, puede ser un signo que facilite el diagnóstico de una enfermedad lisosomal subyacente.

Introduction: dermal melanocytosis includes a spectrum of skin lesions, mongolian spots being one of them. Lysosomal storage diseases are characterized by the accumulation of partially degraded insoluble metabolites in lysosomal compartments due to enzyme deficiency. Deficiency in b-galactosidosisis is the cause of GM1 gangliosidosis and deficiency in a-L-iduronidasa of mucopolysaccharidosis type I. Both have similar clinical presentations. Association of dermal melanocytosis and lysosomal storage diseases is uncommon and misunderstood. Objective: to report the case of two patients with this rare association. Clinical cases: the study presents two boys, 3 and 9 months old, with no remarkable family, pregnancy or delivery history. Both had repeated respiratory tract infections. They presented with developmental delay, central hypotonia and swallowing disorder. Upon clinical examination they showed hepatomegaly, coarse facies and extensive dermal melanocytosis. They were diagnosed with GM1 gangliosidosis and mucopolysaccharidosis type I. Discussion: the cause of this association is not well known. It is hypothesized that accumulation of gangliosides and heparan sulfates stimulates tyrosine-kinase neuronal growth factor receptor, stopping dermal melanocytosis migration. Therefore extensive dermal melanocytosis, in an appropriate clinical setting, may contribute to diagnosing lysosomal storage diseases.

Mucopolisacaridosis de tipo I Hurler: Informe de un caso / Mucopolysaccharidosis I, Hurler syndrome: A case report

La mucopolisacaridosis de tipo I (MPS I), es una enfermedad genética autosómica recesiva de origen lisosomal, caracterizada por la deficiencia de la enzima a-L-iduronidasa. La deficiencia en el catabolismo de los glucosaminoglucanos resulta en su acumulación en diferentes tejidos y órganos. La incidencia global de la MPS I es de 0,99-1,99/100 000 nacidos vivos. Existen tres presentaciones clínicas: Hurler (grave), Hurler-Scheie (moderada) y Scheie (leve). Presentamos el caso de un niño de 10 años de edad a quien se le diagnosticó MPS I, de variedad grave en el año 2006, mediante medición de la actividad enzimática de a-L-iduronidasa en leucocitos. Este caso es el único con diagnóstico confirmado y tratamiento enzimático hasta el momento, en el Perú. Presenta infecciones respiratorias recurrentes, hernia umbilical, opacidad corneal, rasgos toscos, macroglosia, hipoacusia, rigidez articular, estenosis de la válvula pulmonar leve-moderada, manos en garra, retardo mental y retraso del crecimiento. Recibe terapia de reemplazo enzimático desde el año 2008, mostrando mejoría de los síntomas viscerales, más no del daño neurológico.

Mucopolysaccharidosis I (MPS I) is a rare, recessively inherited, lysosomal storage disorder caused by deficiency on the enzyme a-L-iduronidase. This defect results in accumulation of heparan and dermatan sulfate in different tissues and organs due to a deficiency in the catabolism of glycosaminoglycans. The overall incidence of MPS I is 0.99-1.99/100.000 live births. There are three clinical presentations: Hurler (severe), Hurler Scheie (mild) and Scheie (mild). We report the case of a 10-years-old male patient diagnosed with Hurler syndrome, the severe presentation, 5 years ago by enzyme a-L-iduronidase activity measurement in leukocytes; with a history of recurrent respiratory infections, umbilical hernia, corneal opacity, coarse facial features, macroglossia, hearing loss, stiffness of joints, cardiac compromise, claw hands, mental retardation and stunted growth. After enzyme replacement therapy the patient has shown improvement of visceral symptoms, but the neurological damage continuous in progress.

Hurler syndrome with a tuft of hair.

A 2-year-old girl presented with coarse, thick hairy skin all over the body, a tuft of hair in the parietal region, coarse facial features and a prominent forehead with a large tongue, hepatosplenomegaly and skeletal deformities. Mucopolysaccharides excretion spot test of the urine was positive; and an assay for glycosaminoglycans in the urine was also high, which confirmed the clinical diagnosis of Hurler syndrome. We present this rare case to discuss the possibility of the association of mental retardation with a tuft of hair in this syndrome.

The molecular basis of mucopolysaccharidosis type I in two Thai patients.

Two Thai patients diagnosed with Hurler syndrome (mucopolysaccharidosis type 1, MPS I) were found to have no detectable alpha-iduronidase (E.C. 3.2.1.76) activity in leukocytes, while normal Thai children all had significant activity, with a mean of 135 +/- 30 nmol/mg/18h. One patient was heterozygous for A75T (311G>A) and S633L (1986C>T) mutation, previously reported to cause MPS I, together with 9 other heterozygous polymorphisms also found in normal controls. The other patient had the previously described frameshift mutation 252insert C and a new nonsense mutation E299X (983G>T).

Hurler's disease.

Hurler's disease, also known as mucopolysaccharidoses 1H, an autosomal recessive disease due to enzyme alpha-iduronidase deficiency has generally a spectrum of findings involving the eye, skeletal abnormality, organomegaly, joint stiffness, hernia, mental retardation and cardiovascular abnormalities. The two cases presented here are related to each other as brother of 9 years age and sister of 7 years of age with their parents had consanguineous marriage. On ocular examination in both the cases there was dense bilateral corneal opacities. Glycosaminoglycan's level was found to be 4 mg/mmol cr in the first case and 5 mg/mmol cr in the second case. In the first case no ocular treatment was planned and in the second case penetrating keratoplasty was the choice of management.