Physicians

Division Chief, Medical Genetics

Department / Division
Pediatrics / Pediatrics-Medical Genetics

Address
DUMC 103856
595 Lasalle Street, GSRB 1
4th Floor, Room 4010
Durham, NC 27710

Appointment Telephone
919-684-2036

Office Telephone
919-681-9854

Fax Telephone
919-684-8944

Training

• MB BS, Topiwala National College, Bombay (India), 1986

Residency

• Pediatrics, Bombay University (India), 1987-1990
• Pediatrics, Duke University Medical Center, 1990-1991

Fellowship

• Genetics and Metabolism, Duke University Medical Center, 1992-1995

Clinical Interests
Glycogen Storage Disease with focus on Types I, II, III, and Type IX (natural history, long-term complications, and treatment interventions); lysosomal storage diseases such as Gaucher, Pompe, Fabry, Mucopolysaccharidosis (long-term follow-up, natural history, and treatment interventions such as enzyme-replacement therapy, small molecule therapy); Down syndrome (long-term follow-up, management, and interventions to improve cognition); management and treatment of metabolic disorders such as fat acid-oxidation defects, urea-cycle disorders, and mitochondrial disease

Research Interests
RESEARCH INTERESTS

A multidisciplinary approach to care of individuals with genetic disorders in conjunction with clinical and bench research that contributes to:
1)  An understanding of the natural history and delineation of long term complications of genetic disorders
2)  The development of new therapies for genetic disorders through translational research
3)  The development and execution of large multicenter trials to confirm safety and efficacy of potential therapies
4)  Role of antibodies/immune response in patients on therapeutic proteins.

.  Down syndrome:  The Duke Comprehensive Down syndrome (DS) clinic is a multidisciplinary clinic for the clinical care of approximately 700 children and young adults with Down syndrome.  Research interests include establishing best practices for screening of celiac disease, thyroid dysfunction, and iron deficiency anemia.  The Duke DS Research Team is evaluating the effects of cholinesterase inhibitors on cognition and behavior in children and young adults with Down syndrome.  Research issues focus on establishing a standard dosing regimen and developing a sensitive and specific test battery to detect changes in language and cognitive ability.  These studies are being performed at the Duke Clinical Research Unit at Duke.  We are currently involved in a multi-center Phase 2 pediatric trial using donepezil, a cholinesterase inhibitor. The Duke DS Research team is also exploring how a national Down Syndrome registry program could be built and utilized to expand understanding of the condition.

.  Lysosomal Storage Disease:  The Duke Lysosomal Storage Disease (LSD) treatment center follows and treats patients with Pompe, Gaucher, Fabry, Mucopolysaccharidosis and other LSD's.  The Duke Metabolism Clinical Research Team is exploring many aspects of enzyme replacement therapy (ERT), including impact on different systems, differential response, and long term effects.  Other symptomatic and treatment interventions for this category of diseases are also being explored in the context of clinical care.  The care team has extensive experience in the care of infants and adults with Pompe disease and was instrumental in conducting clinical trials and the bench to bedside work that led to the 2006 FDA approval of alglucosidase alfa, the first treatment for this devastating disease.  We are currently focusing on role of antibodies/immune response on patient outcome and role of immunemodulation/immunesuppression as an adjunct to ERT.

.  Glycogen Storage Disease:  We are actively following subjects with all types of Glycogen Storage Disease, with particular emphasis on types I, II, III, IV, VI and IX.  The goal of the treatment team is to better determine the clinical phenotype and long term complications of these diseases.  Attention to disease manifestations observed  in adulthood, such as adenomas and risk for HCC, is of paramount importance in monitoring and treating these chronic illnesses.  We are establishing clinical algorithms for managing adenomas, and the overall management of these patients including cardiac, bone, muscle and liver issues.

.  Neuromuscular disorders:  We are collaborating with neurologists, cardiologists and neuromuscular physicians to serve as a treatment site for clinical trials in these diseases.  We are currently involved in trials of DMD and are working closely on setting up collaborations for studies in SMA.

Industry Relationships and Collaborations (What's this?)

This physician (or a member of their immediate family) has a working relationship (i.e. consulting, research, and/or educational services) with the companies listed below. These relations have been reported to the health system leadership and, when appropriate, management plans are in place to address potential conflicts.

• Amicus Therapeutics
• Enobia
• Genzyme Corporation (Sanofi Aventis)
• National Institutes of Health
• PTC Therapeutics
• Protalix Biotherapeutics Pfizer)
• Roche
• Shire Pharmaceuticals
• Synageva
• Tolerx, Inc.

Representative Publications
Hardy O, Worley G, Lee MM, Chaing S, Mackey J, Crissman B, Kishnani PS. Hypothyroidism in Down syndrome: screening guidelines and testing methodology. Am J Med Genet. 2004 Feb 1;124A(4):436-7. (2004) Abstract

Heller JH, Spiridigliozzi GA, Sullivan JA, Doraiswamy PM, Krishnan RR, Kishnani PS. Donepezil for the treatment of language deficits in adults with Down syndrome: a preliminary 24-week open trial. Am J Med Genet. 2003 Jan 15;116A(2):111-6. (2003) Abstract

Koeberl DD, Millington DS, Smith WE, Weavil SD, Muenzer J, McCandless SE, Kishnani PS, McDonald MT, Chaing S, Boney A, Moore E, Frazier DM. Evaluation of 3-methylcrotonyl-CoA carboxylase deficiency detected by tandem mass spectrometry newborn screening. J Inherit Metab Dis. 2003;26(1):25-35. (2003) Abstract

Koeberl DD, Young SP, Gregersen NS, Vockley J, Smith WE, Benjamin DK Jr, An Y, Weavil SD, Chaing SH, Bali D, McDonald MT, Kishnani PS, Chen YT, Millington DS. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2003 Aug;54(2):219-23. (2003) Abstract

Snyder MJ, Bradford WD, Kishnani PS, Hale LP. Idiopathic hyperammonemia following an unrelated cord blood transplant for mucopolysaccharidosis I. Pediatr Dev Pathol. 2003 Jan-Feb;6(1):78-83. (2003) Abstract

Kishnani PS, Faulkner E, VanCamp S, Jackson M, Brown T, Boney A, Koeberl D, Chen YT. Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia). Vet Pathol. 2001 Jan;38(1):83-91. (2001) Abstract

Kishnani PS, Spiridigliozzi GA, Heller JH, Sullivan JA, Doraiswamy PM, Krishnan KR. Donepezil for Down's syndrome. Am J Psychiatry. 2001 Jan;158(1):143. (2001) Abstract

Mackey J, Treem WR, Worley G, Boney A, Hart P, Kishnani PS. Frequency of celiac disease in individuals with Down syndrome in the United States. Clin Pediatr (Phila). 2001 May;40(5):249-52. (2001) Abstract

Shaiu WL, Kishnani PS, Shen J, Liu HM, Chen YT. Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease. Mol Genet Metab. 2000 Jan;69(1):16-23. (2000) Abstract

Van Hove JL, Kishnani PS, Demaerel P, Kahler SG, Miller C, Jaeken J, Rutledge SL. Acute hydrocephalus in nonketotic hyperglycemia. Neurology. 2000 Feb 8;54(3):754-6. (2000) Abstract

Ahmad A, Amalfitano A, Chen YT, Kishnani PS, Miller C, Kelley R. Dubowitz syndrome: a defect in the cholesterol biosynthetic pathway? Am J Med Genet. 1999 Oct 29;86(5):503-4. (1999) Abstract

Ahmad A, Kahler SG, Kishnani PS, Artigas-Lopez M, Pappu AS, Steiner R, Millington DS, Van Hove JL. Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. Am J Med Genet. 1999 Dec 3;87(4):331-8. (1999) Abstract

Kishnani PS, Boney A, Chen YT. Nutritional deficiencies in a patient with glycogen storage disease type Ib. J Inherit Metab Dis. 1999 Oct;22(7):795-801. (1999) Abstract

Kishnani PS, Sullivan JA, Walter BK, Spiridigliozzi GA, Doraiswamy PM, Krishnan KR. Cholinergic therapy for Down's syndrome. Lancet. 1999 Mar 27;353(9158):1064-5. (1999) Abstract

REFERRED JOURNAL: (1999)

Ahmad A., Miller C., Goldstrum R., Scherer G., Kishnani P. Acampomelic campomelic dysplasia and campomelic dysplasia - A continuous spectrum. J Med. Genet., 1998 (1998)

REFEERED JOURNALS: (1998)

Kishnani PS, Bao Y, Wu JY, Brix AE, Lin JL, Chen YT. Isolation and nucleotide sequence of canine glucose-6-phosphatase mRNA: identification of mutation in puppies with glycogen storage disease type Ia. Biochem Mol Med. 1997 Aug;61(2):168-77. (1997) Abstract

REFEERED JOURNALS: (1997)

Bao Y, Kishnani P, and Chen YT. Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen branching enzyme gene. J Clin Invest. 97:941-948, 1996. (1996)

Kishnani PS, Van Hove JL, Shoffner JS, Kaufman A, Bossen EH, Kahler SG. Acute pancreatitis in an infant with lactic acidosis and a mutation at nucleotide 3243 in the mitochondrial DNA tRNALeu(UUR) gene. Eur J Pediatr. 1996 Oct;155(10):898-903. (1996) Abstract

Kishnani, P., Bangur, A.R., Chen, Y.T., Pulmonary Hypertension in Glycogen Storage Disease Type I (GSD-I). J. Inher. Metab. Dis. 19:213-216, 1996 (1996)

Kishnani, P., Van Hove, J.L.K., Shoffner, J.S., Kauffman, A., Bossen, E.H., Kahler, S.G. Severe infantile lactic acidosis and pancreatitis in a boy heteroplasmic for mt3243 (tRNALeu) mutation. European Journal of Pediatrics. Eur J Pediatr. 155:898-903, 1996 (1996)

REFEERED JOURNALS: (1996)

Rosell, A.M., Wilson, C., Picoli, D.A., Boyle, J., DeClue, T., Kishnani, P., Shen, J., Boney, A., Brown, B., Chen, Y.T. Clinical and laboratory findings in four patients with a variant nonprogressive form of type IV glycogen storage disease. J. Inher. Metab. Dis. 19:51-58, 1996 (1996)

Wang M., Kishnani P., Decker-Phillips M., Kahler, S.G., Chen, Y.T., Godfrey, M. Double mutant fibrillin-1(FBN1) allele in a patient with neonatal marfan syndrome. J Med Genet. 33:760-763, 1996 (1996)

Bao Y., Kishnani P., Chen Y.-T. Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen branching enzyme gene. The Journal of Clinical Investigation, 1995 (In press) (1995)

Kishnani P., Iafolla A.K, McConkie-Rosell A., Kanter R.J., Van Hove J.L.K., Kahler S.G. Hemangiomas, midline raphe, and coarctation of a right aortic arch. A continuous spectrum? Am. J. Med. Genet 59:44-48, 1995 (1995)

Van Hove J.L.K., Kishnani P., Muenzer J., Wenstrup R.J., Summar M.L., Brummond M.R., Lachiewicz A.M., Millington D.S., Kahler S.G. Benzoate and carnitine deficiency in non-ketotic hyperglycinemia. Am. J. Med. Genet 59:444-453, 1995 (1995)