Inherited Metabolic Disease

The Team

Professor Fernando Scaglia

Clinical Services

The Joint Metabolic Clinic at the Prince of Wales Hospital was established in January 1997 with an aim of providing a comprehensive and multidisciplinary care to patients with inherited metabolic diseases (IMD). The clinic is the first of its kind in Hong Kong where it is jointly run by paediatricians, chemical pathologists and dieticians. The clinic sessions take place once to twice per month providing continual care to patients with established inherited metabolic diseases. Majority of our patients have their diagnoses confirmed either by enzymatic assays, cultured fibroblasts studies and / or molecular genetic studies. The clinic also accepts new referrals from other departments within the hospital as well as outside referrals from other hospitals or private practitioners. A monthly metabolic round takes place before each clinic session. This serves as a platform for greater in depth discussion of individual cases among all who are involved in the care of these patients. Individual patients’ progress will be discussed and further investigations and treatment will be planned for. Where necessary, other specialists like orthopedic surgeons, neurosurgeons, ENT surgeons and anesthetists may be invited to participate in the discussion.

 

Hematopoietic Stem Cell Transplantation (HSCT)

In 1998, the Paediatric Bone marrow transplant unit at the Prince of Wales Hospital performed the first bone marrow transplant for an inherited metabolic condition in Hong Kong on a patient with Mucopolyssacharidosis I. A total of 12 transplants for various inherited metabolic conditions have been performed since. 9 of these patients have Lysosomal storage diseases which include Mucopolyssacharidosis I (3 patients), Mucopolyssacharidosis VI (3 patients) and Mucolipidosis II (3 patients).  The other 3 transplants were performed on patients with Adrenoleukodystrophy.

While successful HSCT is a highly effective treatment, none the less it carries with it significant morbidity and mortality, largely due to early and late effects of preparative regimens necessary to facilitate engraftment of donor cells in the recipient. Of the 12 patients who underwent transplant, 5 survived with a much improved quality of life compared with the natural course of their untreated diseases. It is hoped that with more experience, more stringent choice of suitable transplant candidates and the development of various strategies to reduce early and late toxicities of transplantation therapy, HSCT will emerge as a significant treatment modality for a number of these diseases that do not yet have other safer or more effective treatment options.

 

Enzyme Replacement Therapy (ERT) 

Enzyme replacement therapy (ERT) is one of the most significant advancement in the treatment of inherited metabolic diseases over the last 30 years. ERT involves replacing an enzyme constituted by recombinant technology in patients in whom that particular enzyme is deficient or absent. ERT patients receive intravenous infusions containing the synthetic enzyme at regular intervals as a lifelong treatment. Currently, ERT is available for the following Lysosomal diseases: Gaucher disease, Fabry disease, Mucopolyssacharidosis I, II, VI and Pompe disease. ERT is safe and effective. However, it is burdensome to the family and extremely costly accounting for hundreds of thousand to million HK dollars per patient per treatment year.

In Hong Kong, the implementation of ERT for the treatment of Lysosomal storage diseases picked up its pace since 2007 when the Hospital Authority set up an Expert Panel on Enzyme replacement therapy for Rare metabolic diseases. The task of the Expert Panel is to oversee the commissioning of ERT in Hong Kong, recommend treatment guidelines for specific disease groups and to review applications for new as well as old patients for continuation of ERT.  Hospital Authority has assigned three designated treatment centres for enzyme replacement  therapy. The Paediatric department of the Prince of Wales Hospital is one of the 3 designated centres.

 

Enzyme replacement therapy (ERT) has changed the treatment of these patients from previous symptomatic management only to therapeutic interventions now. Though this treatment can greatly modify or attenuate the phenotype, it is not a cure for these diseases.  As individual patients with these diseases live longer, it is anticipated that new disease complication will emerge as the disease phenotype changes in response to therapy.  We thus envisage greater need and demand for more well organized multidisciplinary care for these patients. To enhance better treatment outcome, more coordinated team work and collaboration with other dedicated and experienced specialists like neurosurgeons, orthopedic surgeons and others here at the Prince of Wales Hospital will be needed to tackle these patients’ old as well as ‘new’ problems.

Selected Research Grants 

Sir Robert Ho Tung Charitable Fund

 

Selected Publications

 

  1. J Hui, PMP Yuen, NLS Tang, KF To, ELK Law, JNP Ruiter, RJA Wanders, TF Fok, NM Hjelm.  Reye syndrome’ got another diagnosis.  Journal of Paediatrics and Child Health, Abstract from the 9th Asian Congress of Paediatrics, 23-27 March 1997, 1997;33:S139 (PP16/552).

  2. J Hui, KL Kwok.  A rare but treatable cause of dystonia.  Journal of Paediatrics and Child Health, abstract from the 9th Asian Congress of Paediatrics, 23-27 March 1997, 1997;33:S144 (PP19/572).

  3. KF To, J Hui, NLS Tang, LK Law, NM Hjelm, TF Fok.  Extensive pulmonary infiltration in a Chinese Niemann Pick disease type C (NPc) patient.  Journal of Inherited Metabolic Disease, abstract from SSIEM 36th Annual Symposium, York, 1-4 September 1998, 1998;21:118(A236).

  4. J Hui, TF Leung, E Shoubridge, CK Li, KW Chik, MK Shing, GWK Wong, WL Yeung, NLS Tang, PMP Yuen.  Kearns-sayre syndrome in association with aplastic anaemia.  Journal of Inherited Metabolic Disease, abstract from SSIEM 36th Annual Symposium, York, 1-4 September 1998, 1998;21:78(A156).

  5. NLS Tang, J Hui, LK Law, KF To, JPN Ruiter, L Ijlst, RJA Wanders, CS Ho, TF Fok, PMP Yuen, NM Hjelm.  Primary plasmalemmal carnitine transporter defect manifested with discarboxylic aciduria and impaired fatty acid oxidation. Journal of Inherited Metabolic Disease 1998;21: 423-5.

  6. TF Leung, J Hui, WL Yeung and K Goh.  A Chinese girl with Leigh syndrome: Effect of botulinum toxin on dystonia.  J. Paediatr. Child Health 1998;34:480-2.

  7. Nelson L.S. Tang, Joannie Hui, K.F. To, H.K. Ng, N.M. Hjelm and T.F. Fok.  Severe hypokalemic myopathy in gitelman’s syndrome.  Muscle & Nerve 1999:545-7.

  8. N.L.S. Tang, L.K. Law, J. Hui, K.L. Cheung, Y.Y. Lam, W.L. Yeung and T.F. Fok.  Novel mutations of the Glutaryl-CoA Dehydrogenase Gene in Three Chinese patients with Glutaric aciduria Type I.  The American Journal of Human Genetics 1999;65 (No. 4):A430 (2440).

  9. Joannie Hui, Nelson Tang, KL Cheung, LK Law, Lorena Cheung, Sadie Chen, NM Hjelm, CK Li and TF Fok.  The spectrum of metabolic diseases in Hong Kong Chinese.  The 6th Annual Meeting, Chunchon, Korea, 26-30th October 1999, 1999:44 (VIII-3).

  10. Nelson L.S. Tang, V. Ganapathy, Xiang Wu, Joannie Hui, Pankaj Seth, Patrick M.P. Yuen, T.F. Fok & N.M. Hjelm.  Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency.  Human Molecular Genetics, 1999;8(4):655-660.

  11. J Hui, WL Yeung, N Tang, KW Chik, MK Shing, CK Li, PMP Yuen & TF Fok.  4 Chinese families with adrenoleukodystrophy – clinical presentation and treatment.  The 10th Asian Congress of Paediatrics, Taipei, Taiwan, 26-30 March 2000, 2000:148 (PP24).

  12. Nelson Leung-sang Tang, Hui Joannie, Law Lap-kay, To Ka-fai, Cheung Kam-lau, Hjelm N. Magnus, Patrick Man-pan Yuen & Fok tai-fai.  Primary carnitine deficiency in the Chinese.  Chinese Medical Journal, 2000;113(4):376-380.

  13. Tang, N.L.S., Hui, J., Law E.L.K., Cheung, K.L. and Fok, T.F.  Genetic Mutations of Prevalent Metabolic Diseases in Hong Kong Chinese.  Chinese Congress of Clinical Chemistry & Laboratory Medicine 2000, 2000:49(SC5-4).

  14. J. Hui.  Joint Metabolic Clinic at the Prince of Wales Hospital.  Hong Kong Society of Child Neurology & Developmental Paediatrics Education Bulletin, 2000;1 (No. 3):6-7.

  15. Nelson LS Tang, Joannie Hui, LK Law, KL Cheung, WL Yeung, CK Li, TF Fok.  X-linked Adrenoleukodystrophy (ALD) in Chinese - A mutation analysis.  Journal of Inherited Metabolic Disease, 2000;23 (Suppl. 1):253 (506-P).

  16. Nelson L.S. Tang, Joannie Hui, L.K. Law, Y.Y. Lam, K.Y. Chan, W.L. Yeung, Albert Y.W. Chan, K.L. Cheung and T.F. Fok.  Recurrent and novel mutations of GCDH gene in Chinese glutaric acidemia type I families.  Human Mutation, Mutation in Brief #375 (2000) Online.

  17. Ching-wan Lam, Wai-lan Yeung, Chung-hung Ko, Priscilia MK Poon, Sui-fan Tong, Kwok-yin Chan, Ivan FM Lo, Lisa YS Chan, Joannie Hui, Virginia Wong, Chi-pui Pang, Dennis YM Lo, Tai-fai Fok.  Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome.  J. Med Genet 2000;37.

  18. Nelson L.S. Tang, Joannie Hui, L.K. Law, K.F. To, T.W.L. Mak, K.L. Cheung, Peter Vreken, Ronald J.A. Wanders, T.F. Fok.  Overview of common inherited metabolic diseases in a Sothern Chinese population of Hong Kong.  Clinica Chimica Acta 313 (2001) 195-201.

  19. A. Horinishi, M. Okubo, N.L.S. Tang, J. Hui, K.F. To, T. Mabuchi, T. Okada, H. Mabuchi, T. Murase.  Mutational and haplotype analysis of AGL in patients with  glycogen storage disease type III. J Hum Genet 2002;47:55-59.

  20. J. Hui, ELW Fung, NLS Tang, MHM Chan, KF To & TF Fok.  Instructive Case – Diagnosing Wilson’s disease in a 5-year-old child.  J. Paediatr.  Child Health 2002;38:412-3.

  21. Nelson L.S. Tang, Joannie Hui, Collin K.K. Young, Lawrence T.K. Wong, Derek A. Applegarth, Hilary D, Vallance, L.K. Law, Simon L.M. Fung, Tony W.L. Mak, Y.M. Sung, K.L. Cheung, T.F., Fok.  A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency.  Clinical Biochemistry  2003;36:145-149.

  22. Nelson L.S. Tang, Joannie Hui, Elisabeth Young, Viki Worthington, Ka-Fai To, Kam-Lau Cheung, Chi-Kong Li and Tai-Fai Fok.  A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity.  Molecular Genetics and Metabolism 2003;79:142-145.

  23. L.K. Law, N.L.S. Tang, J. Hui, C.W.K. Lam and T.F. Fok.  3-Methylglutaconic aciduria in a Chinese patient with glycogen storage disease Ib.  J. Inherit. Metab. Dis 2003;26:705-9.

  24. KW Chik, CK Li, MM Shing, J Hui, V Lee, PM Yuen, PC Ng.  Haematopoietic Cell Transplantation (HCT) in I cell disease – Local experience.  Joint Annual Scientific Meeting 2004, Hong Kong, 27 November, 2004, P. 44.

  25. J Hui, KF To, NL Tang.  Homozygous Y55X mutation in NPC 2 gene resulting in Niemann Pick Type C2 disease with early severe pulmonary involvement.  Joint Annual Scientific Meeting 2004, Hong Kong, 27 November, 2004, P. 50.

  26. Joannie Hui.  Inherited Metabolic Diseases in Hong Kong.  The 3rd Hong Kong Medical Genetics Conference 2005:17 (S35).

  27. J. Hui, NL Tang, LK Law, SL Ma, W Huang, KL Cheung, CWL Lam & TF Fok.  Phenotype of Chinese patients with ethylmalonic aciduria due to a gly209SER mutation in the ACADS gene encoding for short-chain acyl-COA dehydrogenase.  The 3rd Hong Kong Medical Genetics Conference 2005:27 (P05).

  28. Wai Lan Yeung, Ching Wan Lam, Joannie Hui, Sui Fan Tong & Shun Ping Wu.  Galactorrhea – A strong clinical clue towards the diagnosis of neurotransmitter disease. Brain and Development, online 10 January 2006.

  29. Joannie Hui, Denise M Kirby, David R. Thorburn, Avihu Boneh.  Decease activities of mitochondrial respiratory chain complexes in non-mitochondrial respiratory chain diseases.  Developmental Medicine & Child Neurology 2006;48:132-136.

  30. Law LK, Tang NLS, Hui J, Pang EWH, Ho CS, Ruiter J, Fok TF, Wanders RJA, Lam CWK.  Detection of fatty acid oxidation defects using simultaneous measurements of total fatty acid b-oxidation flux and acylcarnitine profiling in fibroblasts cultured with H31-palmitate by isotope ratio mass spectrometry and electrospray tandem mass spectrometry.  Journal of Inherited Metabolic Disease 2007;30 (Suppl 1):182P.

  31. Law LK, Tang NLS, Hui J, Chien YH, Hwu WL, Pang EWH, Fung SLM, Ho CS, Ruiter J, Fok TF, Wanders RJA, Lam CWK. Total acylcarnitine level determined by in-vitro probe assay using H31-palmitage can differentiate carnitine uptake defect from other fatty acid oxidation disorders.  Journal of Inherited Metabolic Disease 2007; 30 (Suppl 1): 185P.

  32. Lap-kay Law, Nelson LS Tang, Joannie Hui, Simon LM Fung, Jos Ruiter, Ronald JA Wanders, Tai-fok Fok, Christopher WK Lam.  Novel mutations in ETFDHgene in Chinese patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.  Clinica Chimica Acta 2009;404:95-99.

  33. Joannie Hui and Nelson Tang.  Scaly Rash.  Journal of Paediatrics and Child Health 2010;46 (7-8):441.

  34. J. Hui, KF To, NLS Tang, HC Yau, ELK Law, PC Ng.  Combination of Hyperammonaemia and Tachyarrhythmia in a Newborn with Carnitine-acylcarnitine Translocase Deficiency.  Hong Kong Journal of Paediatrics (New Series) 2010:15:307-310.

  35. Wai-lan Yeung, Kwok-yin Chan, Joannie Hui, Cheuk-wing Fung, Eric Yau, Chun-hung Ko, Ching-wan Lam, Chloe M. Mak, Simon Siu, Louis Low.  Expanding Phenotype and Clinical Analysis of Tryosine Hydroxylase Deficiency.  Journal of child neurology 2010; 26:179-87.

  36. Mak CM, Lam CW, Siu TS, Chan KY, Siu WK, Yeung WL, Hui J, Wong VC, Low LC, Ko CH, Fung CW, Chen SP, Yuen YP, Lee HC, Yau E, Chan B, Tong SF, Tam S, Chan YW.  Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese.  Mol Genet Metab. 2010 Apr; 99(4):431-3.

  37. Eva Lai-wah Fung, Yuan Yuan Ho, Joannie Hui, Jack Ho Wong, Tzi-Bun Ng, Nga-yin Fion Fong, Joerg Klepper, Kwok-Wing Stephen Tsui.  First report of GLUT1 deficiency syndrome in Chinese patients with novel and hot spot mutations in SLC2A1 gene.  Brain & Development 2011;33:170-17.

  38. Chi-kong Lau, Joannie Hui, Fion NY Fong, Ka-fai To, Tai-fai Fok, Nelson LS Tang, Stephen KW Tsui.  Novel mutations in PHKA2 gene in glycogen storage disease type IX patients from Hong Kong, China.  Molecular Genetics and Metabolism 2011;102-222-225.

DEPARTMENT OF PAEDIATRICS

Faculty of Medicine

The Chinese University of Hong Kong

6/F Lui Che Woo Clinical Sciences Building

Prince of Wales Hospital

Shatin

HONG KONG

Office Hours:

08:45 - 13:00 and 14:00 - 17:30 (Mon - Thur)

08:45 - 13:00 and 14:00 - 17:45 (Fri)

Email:  paediatrics@cuhk.edu.hk

Tel:       +852 3505-2851

Fax:      +852 2636-0020

Copyright © 2018.

All Rights Reserved.

The Chinese University of Hong Kong.

  • Instagram Social Icon
  • Facebook Social Icon