PURPOSE: The mucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal storage disorders. They are caused by a deficiency of the enzymes involved in the degradation of glycosaminoglycans. Early recognition is important because recombinant enzyme replacement therapy is now available for MPS. We studied the clinical characteristics of 80 MPS children with the object of determining the epidemiological, clinical and radiological features in Korean MPS children. METHODS: Diagnosis of MPS was confirmed by skin fibroblast enzyme analysis in 80 patients between February 1995 and December 2004. Charts were retrospectively reviewed for clinical and radiological findings, as well as for intelligence and speech evaluations. RESULTS: Hunter syndrome (MPS type II) was the most prevalent type, appearing in 51/80 cases (64 %), followed by Sanfilippo syndrome (MPS III-18%), Hurler syndrome (MPS I-15%), and Morquio syndrome (MPS IV-4%). The average age at diagnosis was 5.5 years (range 1 to 20), and the male-to-female ratio was 4.7: 1. Typical radiographic changes were observed in 45/54 cases (83%). Mitral regurgitation was the most common cardiac defect. Moderate to profound mental retardation and hearing loss were present in 14/35 cases (56%) and 33/38 cases (82%), respectively. Four MPS II patients had bone marrow transplantation, with mixed outcomes. Five MPS I patients are currently on enzyme replacement therapy. CONCLUSION: Our study showed a high proportion of MPS II cases (64%), which may represent population variability. By studying the clinical features of these patients, we hope to alert pediatricians of the warning signs of MPS.
Bone Marrow Transplantation ; Child ; Diagnosis ; Enzyme Replacement Therapy ; Fibroblasts ; Glycosaminoglycans ; Hearing Loss ; Hope ; Humans ; Incidence ; Intellectual Disability ; Intelligence ; Korea ; Mitral Valve Insufficiency ; Mucopolysaccharidoses* ; Mucopolysaccharidosis I ; Mucopolysaccharidosis II ; Mucopolysaccharidosis III ; Mucopolysaccharidosis IV ; Retrospective Studies ; Skin

Consensus ; Humans ; Mucopolysaccharidoses/therapy* ; Mucopolysaccharidosis IV ; Mucopolysaccharidosis VI

Mucopolysaccharidosis type III (MPS III) is a rare genetic disorder caused by lysosomal storage of heparan sulfate. MPS IIIB results from a deficiency in the enzyme alpha-N-acetyl-D-glucosaminidase (NAGLU). Affected patients begin showing behavioral changes, progressive profound mental retardation, and severe disability from the age of 2 to 6 years. We report a patient with MPS IIIB with a long-term follow-up duration. He showed normal development until 3 years. Subsequently, he presented behavioral changes, sleep disturbance, and progressive motor dysfunction. He had been hospitalized owing to recurrent pneumonia and epilepsy with severe cognitive dysfunction. The patient had compound heterozygous c.1444C>T (p.R482W) and c.1675G>T (p.D559Y) variants of NAGLU. Considering that individuals with MPS IIIB have less prominent facial features and skeletal changes, evaluation of long-term clinical course is important for diagnosis. Although no effective therapies for MPS IIIB have been developed yet, early and accurate diagnosis can provide important information for family planning in families at risk of the disorder.
Diagnosis ; Epilepsy ; Family Planning Services ; Follow-Up Studies ; Heparitin Sulfate ; Humans ; Intellectual Disability ; Lysosomal Storage Diseases ; Mucopolysaccharidoses* ; Mucopolysaccharidosis III* ; Pneumonia

Morquio syndrome is a subtype of mucopolysaccharidoses, wherein the accumulation of glycosaminoglycans (GAGs) in various organ systems lead to alteration of anatomy and physiology. Most prominent features are extensive bony abnormalities, which normally require surgical correction. This paper reports the case of a 7-year-old child with Morquio syndrome who successfully underwent correction of genu valgum under general endotracheal anesthesia via asleep induction and videolaryngoscopy, with supplemental peripheral nerve block. The precautions and anesthetic care done to ensure a safe procedure are discussed, especially with anticipation of a possible difficult airway.
Mucopolysaccharidosis IV ; Mucopolysaccharidoses ; Anesthesia

GM2 gangliosidosis II(Sandhoff disease) is a lysosomal storage disease due to deficiency of beta-hexosaminidase activity, transmitted by mode of autosomal recessive. Clinical features are so variable, ranging from infantile onset resulting death before 4 years, to subacute or chronic forms with more slowly progressive neurologic condition. We experienced a case of GM2 gangliosidosis II in a 14 months old male who had developmental deterioration and seizures, so we report and review the related literatures.
beta-N-Acetylhexosaminidases ; Gangliosidoses, GM2* ; Hexosaminidases ; Humans ; Infant ; Lysosomal Storage Diseases ; Male ; Seizures

PURPOSE: To investigate the ophthalmologic manifestations of Korean patients with Gaucher disease. METHODS: Clinical records of 5 patients who were referred to the pediatric ophthalmology clinic of Seoul National University Bundang Hospital after diagnosis of Gaucher disease at the genetics clinic of Ajou University Hospital between 2007 and 2008 were retrospectively reviewed. RESULTS: Five patients with type 3 Gaucher disease had hepatosplenomegaly and oculomotor apraxia, and 4 patients had growth and developmental delay. The most commonly detected genetic mutation was L444P. In addition, P201H, F2131, R257Q, and D315E+Rec 1b were identified. Five patients had oculomotor apraxia and limitation of abduction, and 4 patients had esotropia. One of the 4 patients who showed combined limitation of abduction, oculomotor apraxia, and esotropia, yet did not have growth and developmental delay. CONCLUSIONS: Most of the patients who were referred for ocular motor abnormalities with Gaucher disease showed a limitation of abduction, oculomotor apraxia, and esotropia. In patients with a limitation of abduction, oculomotor apraxia, and esotropia, Gaucher disease should be considered. Ophthalmologic examination is essential for subtyping and prognosing Gaucher disease.
Apraxias ; Diagnosis ; Esotropia ; Gaucher Disease* ; Genetics ; Growth and Development ; Humans ; Lysosomal Storage Diseases ; Ophthalmology ; Retrospective Studies ; Seoul

Sphingolipidoses are a subgroup of lysosomal storage disorders. They are characterized by relentless progressive storage in affected organs and concomitant functional impairments. No overall screening procedure for these disorders is available. Their course and appearance, however, are usually characteristic and, together with relevant technical procedures such as magnetic resonance imaging (MRI), clinical neurophysiology, ophthalmologic examination, etc., a provisional diagnosis can be made, after which enzymatic diagnosis can close the gap in the diagnostic process. Subgroups of sphingolipidoses are grouped together, such as disorders with prominent hepatosplenomegaly (Niemann-Pick A, B and Gaucher disease) and disorders with central and peripheral demyelination (metachromic leukodystrophy and Krabbe disease). Farber disease and Fabry disease are unique in themselves. The last decade has seen hopeful progress in therapeutic strategies, especially for Gaucher disease. Therefore, emphasis of this review has been placed on these new developments.
Demyelinating Diseases ; Diagnosis ; Fabry Disease ; Farber Lipogranulomatosis ; Gangliosidoses, GM2 ; Gangliosidosis, GM1 ; Gaucher Disease ; Hope ; Leukodystrophy, Globoid Cell ; Magnetic Resonance Imaging ; Mass Screening ; Neurophysiology ; Niemann-Pick Diseases ; Sphingolipidoses*

PURPOSE: Gaucher disease (GD) is the most common lysosomal storage disease caused by beta-glucocerebrosidase (GBA) deficiency. Oral substrate reduction therapy with miglustat (Zavesca®) was approved for the treatment of adults with GD type 1, for whom enzyme replacement therapy (ERT) is unsuitable or not a therapeutic option. In this study, we report the effect of miglustat (Zavesca®) in three Korean GD patients. MATERIALS AND METHODS: Clinical findings comprising age at diagnosis, presenting signs, laboratory findings at diagnosis, GBA activity and mutations, and clinical courses of the three patients were reviewed. RESULTS: Miglustat was administered to three patients who reported allergic reactions during intravenous imiglucerase infusions. One patient withdrew after 15 months of miglustat administration owing to continuous elevation of disease biomarker levels (chitotriosidase, acid phosphatase, and angiotensin-converting enzyme). Poor adherence to medication was suspected but was denied by the patient. In the other two patients, platelet count and levels of hemoglobin and other biomarkers remained stable during miglustat administration. However, they suffered from severe diarrhea and weight loss, which led to miglustat discontinuation after 1 and 12 months of administration. CONCLUSION: Our study shows that although miglustat is suggested to GD patients as an alternative treatment to ERT, significant adverse reactions may lead to discontinuation of miglustat. In addition, it is difficult to monitor the drug adherence.
Acid Phosphatase ; Adult ; Biomarkers ; Diagnosis ; Diarrhea ; Enzyme Replacement Therapy ; Gaucher Disease* ; Glucosylceramidase ; Humans ; Hypersensitivity ; Lysosomal Storage Diseases ; Platelet Count ; Weight Loss

Type 1 Gaucher disease is one of the most common genetic lysosomal storage disease caused by the deficiency of glucocerobrosidase. Deficiency of this enzyme results in accumulation of glucoceramide in the macrophage and leads to hepatosplenomegaly, pancytopenia, bone damage and sometimes can be fatal. Recently, enzyme replacement has been considered as a major therapeutic strategy and about 2,000 patients have been treated successfully by macrophage- targeted human placental glucocerebrosidase worldwide. Our patient was a 16-month-old female child who visited our clinic with complaints of petechiae and splenomegaly. Complete blood count showed pancytopenia. Bone marrow study revealed Gaucher cells. Glucocerebrosidase activity was remarkably reduced. We infused macrophage-targeted (mannose-terminated) glucocerebrosidase into the patient for 18 months (30U/kg every 2 weeks for 2 months, 10U/kg every other day for 6 months, 5U/kg every other day for 6 months, and 20U/kg every 2 weeks for 4 months). After treatment, substantial increase in hemoglobin and thrombocyte counts was observed. In addition, hepatic and splenic volumes were strikingly decreased on volumetric CT scan. She felt better after treatment and catch-up growth has been achieved. In conclusion, enzyme replacement therapy should be considered as a major therapeutic option in type 1 Gaucher disease.
Blood Cell Count ; Blood Platelets ; Bone Marrow ; Child ; Cone-Beam Computed Tomography ; Enzyme Replacement Therapy ; Female ; Gaucher Disease* ; Glucosylceramidase ; Humans ; Infant ; Lysosomal Storage Diseases ; Macrophages ; Pancytopenia ; Purpura ; Splenomegaly

Cystinosis, an autosomal recessively inherited lysosomal storage disease, results from impaired transport of the amino acid cystine out of cellular lysosomes. The consequent accumulation and crystallization of cystine destroys tissues, causing growth retardation, Fanconi syndrome, renal failure, eye problems, and endocrinopathies. The gene for cystinosis, CTNS, was mapped to chromosome 17p13. The diagnosis of cystinosis was made by measuring the leukocyte cystine content. The presence of typical corneal crystals on slit-lamp examination is also diagnostic. Since treatment with cysteamine has proved extremely effective, early diagnosis and treatment are critical aspects. We experienced a typical case of cystinosis in a 12-year-old boy with growth retardation.
Child ; Crystallization ; Cysteamine ; Cystine ; Cystinosis* ; Diagnosis ; Early Diagnosis ; Fanconi Syndrome ; Humans ; Leukocytes ; Lysosomal Storage Diseases ; Lysosomes ; Male