RESUMEN
BACKGROUND: Several studies have discovered an association between infant feeding practices and puberty timing; however, most have involved female cohorts. We investigated the association between infant feeding practices and the timing of peak height velocity in boys and girls. METHODS: Data on infant feeding methods and anthropometric measurements were collected from a nationwide Japanese birth cohort study. The age at peak height velocity (APV, years) was estimated and compared. Subsequently, the effects of breastfeeding duration were analyzed. RESULTS: Of the 13,074 eligible participants, 650, 9455, and 2969 were formula-, mixed-, and exclusively breastfed, respectively. Among girls, the mean APV was significantly later in the mixed-fed (standardized regression coefficient (ß): 0.094, 95% confidence interval (CI): 0.004-0.180) and exclusively breastfed (ß: 0.150, 95% CI: 0.056-0.250) groups than in the formula-fed group. Among boys, the mean APV was not significantly different among the three groups; however, a sensitivity analysis that excluded preterm birth revealed more significantly delayed APV in the breastfed-only group compared to the formula-fed group. Furthermore, a multiple linear regression model revealed that a longer breastfeeding period was associated with later APV. CONCLUSIONS: Infant breastfeeding practices can affect the timing of peak height velocity in both boys and girls. IMPACT: Several studies have discovered an association between infant feeding practices and puberty timing; however, most have involved female cohorts. Age at peak height velocity, derived from longitudinal height measurements, is a useful marker of secondary sexual maturity milestones in boys and girls. A Japanese birth cohort study revealed that breastfed children had a later age at peak height velocity than their formula-fed counterparts; this was more prominent among girls than boys. Furthermore, a duration-effect relationship was observed, where longer breastfeeding duration was associated with a later age at peak height velocity.
Asunto(s)
Lactancia Materna , Conducta Alimentaria , Masculino , Niño , Humanos , Lactante , Femenino , Estudios de Cohortes , Japón , Estudios LongitudinalesRESUMEN
Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.
Asunto(s)
Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Hipotiroidismo/diagnóstico , Recién Nacido Pequeño para la Edad Gestacional , Glándula Tiroides/efectos de los fármacos , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/fisiopatología , Terapia de Reemplazo de Hormonas/efectos adversos , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/farmacología , Humanos , Hipotiroidismo/fisiopatología , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Japón , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/fisiopatología , Pruebas de Función de la Tiroides/métodos , Glándula Tiroides/fisiopatología , Hormona Liberadora de Tirotropina/farmacología , Factores de TiempoRESUMEN
Mucopolysaccharidosis type I (MPS I) is a rare inherited metabolic disorder caused by defects in alpha-L-iduronidase (IDUA), a lysosomal protein encoded by IDUA gene. MPS I is a progressive multisystemic disorder with a wide range of symptoms, including skeletal abnormalities and cognitive impairment, and is characterized by a wide spectrum of severity levels caused by varied mutations in IDUA. A human iPSC line was established from an attenuated MPS I (Scheie syndrome) patient carrying an IDUA gene mutation (c.266Gâ¯>â¯A; p.R89Q). This disease-specific iPSC line will be useful for the research of MPS I.
Asunto(s)
Línea Celular , Iduronidasa/genética , Células Madre Pluripotentes Inducidas , Mucopolisacaridosis I/genética , Femenino , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVES: To assess the effects of growth hormone (GH) on lipid profiles in children and whether the effect is pharmacological. METHODS: The authors determined serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and low-density lipoprotein cholesterol (LDL-C) every year during 3-y GH treatment in 48 GH deficient (GHD) short children and 22 children with short stature born small for gestational age (SGA). RESULTS: The abnormally high levels of TC, non-HDL-C, and LDL-C showed a high frequency in GHD short children compared with epidemiological studies in Japan. The high prevalence of high level of TC was also shown in SGA short children. Three-year GH treatment decreased serum TC, non-HDL-C, and LDL-C levels in both patient groups. CONCLUSIONS: GH treatment is clearly a pharmacological therapy in SGA short children and so may also be in GHD short children at the Japanese standard therapeutic dose. Taken together, GH improves lipid profiles, and its effect has the possibility of medical properties.
Asunto(s)
Enanismo Hipofisario/tratamiento farmacológico , Hormona de Crecimiento Humana/farmacología , Lípidos/sangre , Niño , Preescolar , Femenino , Hormona del Crecimiento , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Recién Nacido , Masculino , Maduración SexualRESUMEN
Turner syndrome is a chromosomal disorder usually caused by complete deletion of an X chromosome, with deletion in the short arm of the X chromosome being a rare cause of the condition. Patients with Turner syndrome commonly develop hypertension, and associated vascular complications such as aortic dissection or cerebral hemorrhage have been reported. Cerebral hemorrhage in Turner syndrome is a rare complication, and only a few reports have been published. In these reports, all patients have XO karyotypes or a mosaic type as the cause of Turner syndrome, while no other Turner syndrome types have been documented. In this report, we present for the first time a patient with Turner syndrome caused by deletion in the short arm of the X chromosome who experienced hypertensive hemorrhage as a late complication.
Asunto(s)
Hemorragia Cerebral , Deleción Cromosómica , Cromosomas Humanos X/genética , Hemorragia Intracraneal Hipertensiva , Síndrome de Turner/complicaciones , Adulto , Femenino , Humanos , Náusea/etiología , Síndrome de Turner/genéticaRESUMEN
Early initiation of enzyme replacement therapy (ERT) has demonstrated clinical benefit in patients with mucopolysaccharidosis type VI (MPS VI), a progressive, multisystem autosomal recessive lysosomal disorder caused by N-acetylgalactosamine-4-sulphatase (ASB) deficiency and the consequent accumulation of glycosaminoglycan. A previous case report highlighted that 3 years of ERT with recombinant human ASB (galsulfase) was well tolerated and effective in two Japanese siblings with MPS VI who initiated ERT at 5.6 years and 6 weeks of age, respectively. This report describes 10-year follow-up data from these two siblings who continued ERT with weekly infusions of galsulfase 1 mg/kg. Ten years of ERT was well tolerated, and the older sibling reached puberty. He had typical MPS VI phenotypic features, but exhibited significant improvement in shoulder range of motion and had largely unchanged hearing and cardiac function. His skeletal deformity remained unchanged. In contrast, in the younger sibling, typical symptoms of MPS VI, including progressive dysmorphic facial features, hepatosplenomegaly, and hearing impairment were largely absent. Her joint mobility was preserved, although skeletal deformity, including claw-hand deformity, was observed. Both siblings had progressive corneal clouding. The observations in these two patients suggest that early ERT initiated in newborns can be well tolerated and effective in preventing or slowing MPS VI disease progression, but is limited in terms of its effects on bone symptoms. For this, new approaches or bone-targeting treatments would be necessary.
RESUMEN
Gaucher disease (GD) is the most common type of lysosomal storage disease, with type 2 being the most severe subtype. Type 2 GD patients suffer significant progressive neurological impairment, including spasticity, opisthotonus, seizure, and apnea. The recently developed enzyme replacement therapy (ERT) has shown therapeutic benefit for GD. However, as the enzymes do not cross the blood-brain barrier, ERT does not ameliorate neurological impairment in GD. Intrathecal baclofen therapy (IBT) is indicated for spastic neurological diseases, such as cerebral palsy, and studies have shown its therapeutic benefit in improving several manifestations of GD, such as scoliosis caused by muscle spasticity and respiratory function. To date, the potential benefits of IBT for treating lysosomal storage diseases such as GD have not been examined. Here we provide the first report of a patient with type 2 GD treated with IBT, and demonstrate its therapeutic benefit in ameliorating the neurological aspects of this disease.
Asunto(s)
Baclofeno/administración & dosificación , Enfermedad de Gaucher/diagnóstico por imagen , Enfermedad de Gaucher/tratamiento farmacológico , Bombas de Infusión Implantables , Relajantes Musculares Centrales/administración & dosificación , Preescolar , Femenino , Humanos , Inyecciones EspinalesRESUMEN
We report a 16-year-old man with disorders of tetrahydrobiopterin metabolism due to dihydropteridine reductase (DHPR) deficiency. He revealed moderate mental retardation, parkinsonism, and spastic paralysis with levodopa and 5-hydroxytryptophan (5-HTP) supplementation from the age of 2 months. Brain MRI showed high intensity areas in bilateral frontal and posterior deep white matter on fluid-attenuated inversion recovery (FLAIR). Coronal FLAIR image showed a high signal in bilateral pyramidal tracts. Single photon computed tomography (SPECT) imaging of the dopamine transporter was normal. This imaging indicates no dopaminergic cell loss. Our patient had no motor fluctuations or dyskinesias. Early diagnosis and replacement treatment might lead to a favorable outcome.
RESUMEN
Acromicric dysplasia (AD) and geleophysic dysplasia (GD) are rare skeletal dysplasias characterized by short stature, acromelia, joint contracture, hepatomegaly, hoarseness and respiratory distress. Compared with GD, AD presents with milder clinical and radiological features. Radiological findings of AD and GD consist of shortened tubular bones of the hands and feet, and deformed capital femoral epiphyses. The genetic cause of AD and some cases of GD was shown to be mutations in the transforming growth factor (TGF) ß-binding protein-like domain 5 of the fibrillin 1 gene (FBN1), which is also mutated in Marfan syndrome. In the present study, we report and compare the highly varied clinical and radiological features of three Japanese AD/GD children. Our patients, harboring FBN1 mutations p.Tyr1699Cys, p.Ser1750Arg, and p.Gly1762Ser, shared common clinical symptoms such as severe short stature, acromelia and hepatomegaly. Short tubular bones of hands and deformities of femur heads are common radiological features of our patients.
Asunto(s)
Enfermedades del Desarrollo Óseo/genética , Fibrilina-1/genética , Hepatomegalia/genética , Deformidades Congénitas de las Extremidades/genética , Mutación/genética , Enfermedades del Desarrollo Óseo/diagnóstico por imagen , Enfermedades del Desarrollo Óseo/patología , Niño , Preescolar , Femenino , Hepatomegalia/diagnóstico por imagen , Hepatomegalia/patología , Humanos , Japón , Deformidades Congénitas de las Extremidades/diagnóstico por imagen , Deformidades Congénitas de las Extremidades/patología , Masculino , Pronóstico , Radiografía/métodosRESUMEN
BACKGROUND: This study assessed whether non-fasting lipid markers could be substituted for fasting markers in screening for dyslipidemia, whether direct measurement of non-fasting low-density lipoprotein cholesterol [LDL-C (D)] could be substituted for the calculation of fasting LDL-C [LDL-C (F)], and the utility of measuring non-high-density lipoprotein cholesterol (non-HDL-C). METHODS: In 33 children, the lipid profile was measured in the non-fasting and fasting states within 24 h. Correlations were examined between non-fasting LDL-C (D) or non-HDL-C levels and fasting LDL-C (F) levels. RESULTS: Non-fasting triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C (D), and non-HDL-C levels were all significantly higher than the fasting levels, but the mean difference was within 10% (except for TG). Non-fasting LDL-C (D) and non-HDL-C levels were strongly correlated with the fasting LDL-C (F) levels. CONCLUSIONS: In conclusion, except for TG, non-fasting lipid parameters are useful when screening children for dyslipidemia. Direct measurement of non-fasting LDL-C and calculation of non-fasting non-HDL-C could replace the calculation of fasting LDL-C because of convenience.
Asunto(s)
Biomarcadores/análisis , Enanismo/fisiopatología , Dislipidemias/fisiopatología , Ayuno/fisiología , Lípidos/análisis , Adolescente , Niño , Preescolar , HDL-Colesterol/análisis , LDL-Colesterol/análisis , Femenino , Estudios de Seguimiento , Humanos , Lipoproteínas/análisis , Masculino , Pronóstico , Estudios Prospectivos , Triglicéridos/análisisRESUMEN
Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or dihydropteridine reductase (DHPR), respectively. Although BH4 metabolism disorders and its metabolisms have been studied, it is unclear how gene variants cause aberrant DA synthesis in patient neurons. Here, we generated induced pluripotent stem cells (iPSCs) from BH4 metabolism disorder patients with PTPS or DHPR variants, corrected the gene variant in the iPSCs using the CRISPR/Cas9 system, and differentiated the BH4 metabolism disorder patient- and isogenic control iPSCs into midbrain DA neurons. We found that by the gene correction, the BH4 amount, TH protein level and extracellular DA level were restored in DA neuronal culture using PTPS deficiency iPSCs. Furthermore, the pharmacological correction by BH4 precursor sepiapterin treatment also improved the phenotypes of PTPS deficiency. These results suggest that patient iPSCs with BH4 metabolism disorders provide an opportunity for screening substances for treating aberrant DA synthesis-related disorders.
Asunto(s)
Biopterinas/análogos & derivados , Dopamina/genética , Células Madre Pluripotentes Inducidas/metabolismo , Enfermedades Metabólicas/genética , Enfermedad de Parkinson/genética , Biopterinas/metabolismo , Diferenciación Celular/genética , Dopamina/biosíntesis , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Genotipo , Humanos , Cariotipo , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Pterinas/metabolismo , Tirosina 3-Monooxigenasa/genéticaRESUMEN
We assessed the clinical characteristics and efficacy of neurotransmitters and levetiracetam in a patient with hyperphenylalaninemia due to dihydropteridine reductase (DHPR) deficiency who developed epileptic seizures. A boy with DHPR deficiency, who had been successfully treated with tetrahydrobiopterin (BH4), levodopa, and 5-hydroxytryptophan (5-HTP) since he was 2 months old, started having monthly episodes of blurred vision, loss of consciousness, and falls at the age of 12 years. He was taking BH4 510 mg/day, levodopa 670 mg/day, 5-HTP 670 mg/day, and entacapone 300 mg/day. We evaluated the seizure semiology, EEG findings, and efficacy of levodopa, 5-HTP, and levetiracetam (LEV). His seizures were comprised of an abrupt loss of awareness and eye deviation to the right. Interictal EEG showed slightly slow posterior-dominant rhythm in 7-8 Hz; intermittent, irregular slowing in the bilateral parieto-occipital region; and multiregional independent spikes in bilateral hemispheres. Ictal EEG showed a seizure pattern starting at the left temporal region. Brain MRI showed diffuse signal increase of deep white matter on T2-weighted and FLAIR images. Dosage increase of levodopa to 1340 mg/day, of 5-HTP to 1500 mg/day, or of both did not suppress seizures. Levetiracetam 2000 mg/day markedly reduced seizures without any adverse events. Patients with DHPR deficiency can develop epileptic seizures of partial onset which can be successfully and safely treated with LEV.
RESUMEN
Methionine adenosyltransferase I/III deficiency (MAT I/III deficiency) is an inborn error of metabolism that results in isolated persistent hypermethioninemia. Definitive diagnosis is now possible by molecular analyses of the MAT1A gene. Based on newborn screening (NBS) data collected between 2001 and 2012 in Hokkaido, Japan, the estimated incidence of MAT I/III deficiency was 1 in 107,850. 24 patients (13 males, 11 females) from 11 prefectures in Japan were referred to our laboratory for genetic diagnosis of MAT I/III deficiency. They were all found between 1992 and 2012 by the NBS program in each region. In these 24 individuals, we identified 12 distinct mutations; 14 patients were heterozygous for an R264H mutation; R264H caused an autosomal dominant and clinically benign phenotype in each case. The mutations in the other 10 patients showed autosomal recessive inheritance and included eight novel MAT1A mutations. Putative amino acid substitutions at R356 were observed with six alleles (three R356P, two R356Q, and one R356L). MAT I/III deficiency is not always benign because three of our cases involved brain demyelination or neurological complications. DNA testing early in life is recommended to prevent potential detrimental neurological manifestations.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Metionina Adenosiltransferasa/deficiencia , Metionina/metabolismo , Tamizaje Neonatal , Alelos , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encéfalo , Femenino , Glicina N-Metiltransferasa/deficiencia , Humanos , Recién Nacido , Japón , Masculino , Metionina/genética , Metionina Adenosiltransferasa/genética , Mutación , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/genética , FenotipoRESUMEN
Enzyme replacement therapy (ERT) for Fabry disease does not show a clear benefit in angiokeratoma. We describe two Japanese siblings with Fabry disease, who were diagnosed when angiokeratomas were found on the older sibling at the age of 13 years. Neither of the boys complained of pain, while both suffered from hypohidrosis. We evaluated the safety and efficacy of ERT with recombinant human agalsidase alfa (Replagal®, Dainippon-Sumitomo Pharma. Co., Osaka, Japan) in these siblings over a 5-year period. In both siblings, sweating was observed 3 months after the initiation of ERT, which motivated them to adhere to ERT. Pain sensation was regained after 12 to 36 months of ERT, followed by a decrease after 48 to 60 months. Angiokeratomas on the lateral side of the knee of the older sibling partially disappeared after 48 months of ERT. Although the height of both siblings at baseline was lower than the corresponding average age-related heights in the normal Japanese population, during ERT they were within, or close to, the average +1 standard deviation in the non-Fabry population. Their growth rate seemed to indicate catch-up growth. Other clinical symptoms were maintained at baseline levels. Immunoglobulin G anti-agalsidase alfa antibodies were not detected in both sibling during ERT, and no infusion-associated reaction was observed. The treatment was generally well tolerated. ERT was a safe and effective treatment for angiokeratoma and neuropathic pain for these two siblings with Fabry disease.
Asunto(s)
Angioqueratoma/tratamiento farmacológico , Terapia de Reemplazo Enzimático , Enfermedad de Fabry/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , alfa-Galactosidasa/uso terapéutico , Adolescente , Angioqueratoma/patología , Niño , Terapia de Reemplazo Enzimático/efectos adversos , Enfermedad de Fabry/diagnóstico , Humanos , Masculino , Linaje , Hermanos , Resultado del Tratamiento , Trihexosilceramidas/sangre , Trihexosilceramidas/orina , alfa-Galactosidasa/efectos adversosRESUMEN
Methionine adenosyltransferase I/III (MAT I/III) deficiency, caused by mutations in the MAT1A gene, is an inherited metabolic disorder characterized by persistent hypermethioninemia, usually detected by newborn mass screening. There is a wide range of clinical manifestations, from completely asymptomatic to neurological problems associated with brain demyelination. Physiological role of S-adenosylmethionine (SAM), the metabolic product of methionine catalyzed by MAT, in the central nervous system has been investigated in vivo and in vitro, and case reports demonstrated an effectiveness of supplementary treatment of SAM in the improvement of neurological development and myelination. Methionine restriction can be an additional therapeutic strategy because hypermethioninemia alone may be neurotoxic; however, lowering methionine carries a risk to decrease the synthesis of SAM.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Encéfalo/metabolismo , Enfermedades Desmielinizantes/metabolismo , Metionina Adenosiltransferasa/metabolismo , Metionina/metabolismo , S-Adenosilmetionina/metabolismo , Alelos , Errores Innatos del Metabolismo de los Aminoácidos/dietoterapia , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/patología , Encéfalo/patología , Enfermedades Desmielinizantes/dietoterapia , Enfermedades Desmielinizantes/genética , Enfermedades Desmielinizantes/patología , Dieta , Pruebas Genéticas , Glicina N-Metiltransferasa/deficiencia , Humanos , Recién Nacido , Isoenzimas/genética , Isoenzimas/metabolismo , Metionina Adenosiltransferasa/deficiencia , Metionina Adenosiltransferasa/genética , Mutación , S-Adenosilmetionina/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
Reported is a female patient with methionine adenosyltransferase I/III (MAT I/III) deficiency, who was found to have pronounced hypermethioninemia on newborn mass spectroscopy screening, and had two compound heterozygous missense mutations in the gene encoding human MAT1A protein. Hypermethioninemia persisted and her mental development was deficient. At 4 years and 8 months, we started with the supplementary treatment of S-adenosylmethionine, the metabolic product of methionine catalyzed by MAT, which was effective in her neurological development.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Metionina Adenosiltransferasa/deficiencia , Metionina Adenosiltransferasa/genética , S-Adenosilmetionina/uso terapéutico , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Niño , Femenino , Humanos , Metionina/deficiencia , Metionina/metabolismo , Mutación MissenseRESUMEN
Mucopolysaccharidosis type VI (MPS VI) is a progressive, multisystem autosomal recessive lysosomal disorder resulting from deficient N-acetylgalactosamine-4-sulphatase (ASB) and the consequent accumulation of glycosaminoglycan (GAG). Preclinical and clinical studies had demonstrated clinical benefits of early initiation of systemic therapies in patients with MPS. In this case report, two siblings with MPS VI started enzyme replacement therapy (ERT) with weekly infusions of recombinant human ASB (Galsulfase) at 1mg/kg. Sibling 1 started ERT 5.6 years of age and Sibling 2 was 6 weeks old. The disease status in these two siblings prior to and for no less than 36 months of ERT was followed up and compared. The treatment was well tolerated by both siblings. During 36 months of ERT, symptoms typical of MPS VI including short stature, progressive dysmorphic facial features, hepatosplenomegaly, hearing impairment, corneal clouding, and dysostosis multiplex were largely absent in the younger sibling. Her cardiac functions and joint mobility were well preserved. On the other hand, her affected brother had typical MPS VI phenotypic features described above before commencing ERT at the equivalent age, of 3 years. There was significant improvement in the shoulder range of motion and hearing loss after 36 months of treatment and cardiac function was largely preserved. His skeletal deformity and short stature remained unchanged. The results showed that early ERT initiated at newborn is safe and effective in preventing or slowing down disease progression of MPS VI including bone deformities. These observations indicate that early diagnosis and treatment of MPS VI before development of an irreversible disease is critical for optimal clinical outcome.