Research Overview

Our major interest is the development of better diagnostic tools and treatments of metabolic diseases.

For the past two decades, we have focused our studies on phenylketonuria (PKU). PKU is a genetic disease in which the body is deficient in an enzyme, phenylalanine hydroxylase (PAH), that breaks down the amino acid phenylalanine. Without a special diet or other intervention within the first months of life, PKU patients can develop serious medical complications, including intellectual disability.

A new treatment for PKU
In an international clinical trial, we have shown that in some patients, BH4 (the natural cofactor of PAH) reduces phenylalanine levels and allows their severe dietary restrictions to be relaxed. The drug, known as Kuvan, is the first and only drug now approved specifically for PKU.

Maternal PKU
Expectant mothers with PKU are at great risk of having children with birth defects or intellectual disability. Scientific studies suggest that if these women go on a special diet, preferably before conception, these risks are severely reduced. In a long-term study, we are monitoring the health and well being of children born to mothers with PKU to determine the extent of these risks and, in the future, to better predict their health outcomes.

In 2008, we joined a national long-term study of the urea cycle disorders, a group of diseases in which toxic levels of ammonia build up in the bloodstream, causing brain damage and death. With new drugs now available to reduce blood ammonia levels, we hope this observational study, which began in 2006, will provide insight on how to most effectively treat these patients.

About Harvey Levy

Harvey Levy is a Senior Physician in Medicine at Boston Children's Hospital and a Professor of Pediatrics at Harvard Medical School. He was formerly the Director of the Metabolic Program at Boston Children's Hospital and currently serves as an attending physician within the program.

A strong advocate of the expansion of newborn screening, Levy was instrumental in Massachusetts becoming the first state to include 20 additional metabolic disorders in its newborn screening program. He is currently Chairman of the Standing Committee for the American College of Medical Genetics (ACMG)'s Newborn Screening Translational Research Network (NBSTRN, a five-year, federally sponsored program that aims to better predict the outcomes of children with metabolic disorders identified by newborn screening. He also chairs the Workgroup for ACT Sheets of the ACMG. These sheets inform clinicians about the nature and treatment of the specific metabolic disorder identified.

Levy received his MD from the Medical College of Georgia. He then completed an internship in pediatrics at Boston City Hospital, residencies in pediatric pathology at Columbia-Presbyterian Medical Center, pediatrics at Johns Hopkins Hospital, pediatrics at Boston City Hospital and a research fellowship in metabolic disorders at Massachusetts General Hospital. He is board-certified in Pediatrics, Medical Genetics and Clinical Biochemical Genetics.

Researcher Services

Researcher Areas

  • Genetics

Research Departments

Research Divisions

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Stroup BM, Nair N, Murali SG, Broniowska K, Rohr F, Levy HL, Ney DM. Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria. J Nutr. 2018 Feb 01; 148(2):194-201. View abstract
  2. Rodan LH, Aldubayan SH, Berry GT, Levy HL. Acute Illness Protocol for Maple Syrup Urine Disease. Pediatr Emerg Care. 2018 Jan; 34(1):64-67. View abstract
  3. Stroup BM, Ney DM, Murali SG, Rohr F, Gleason ST, van Calcar SC, Levy HL. Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropeptide Medical Foods. J Nutr Metab. 2017; 2017:6859820. View abstract
  4. Rodan LH, Aldubayan SH, Berry GT, Levy HL. Acute Illness Protocol for Urea Cycle Disorders. Pediatr Emerg Care. 2017 Nov 14. View abstract
  5. Stroup BM, Murali SG, Nair N, Sawin EA, Rohr F, Levy HL, Ney DM. Dietary amino acid intakes associated with a low-phenylalanine diet combined with amino acid medical foods and glycomacropeptide medical foods and neuropsychological outcomes in subjects with phenylketonuria. Data Brief. 2017 Aug; 13:377-384. View abstract
  6. Ney DM, Murali SG, Stroup BM, Nair N, Sawin EA, Rohr F, Levy HL. Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria. Mol Genet Metab. 2017 Jun; 121(2):96-103. View abstract
  7. Aldubayan SH, Rodan LH, Berry GT, Levy HL. Acute Illness Protocol for Fatty Acid Oxidation and Carnitine Disorders. Pediatr Emerg Care. 2017 Apr; 33(4):296-301. View abstract
  8. Aldubayan SH, Rodan LH, Berry GT, Levy HL. Acute Illness Protocol for Organic Acidemias: Methylmalonic Acidemia and Propionic Acidemia. Pediatr Emerg Care. 2017 Feb; 33(2):142-146. View abstract
  9. Landau YE, Waisbren SE, Chan LM, Levy HL. Long-term outcome of expanded newborn screening at Boston children's hospital: benefits and challenges in defining true disease. J Inherit Metab Dis. 2017 Mar; 40(2):209-218. View abstract
  10. Rosenblatt DS, Watkins D, Rajabi F, Levy HL. Confounding factors in identification of disease-resilient individuals. Nat Biotechnol. 2016 Nov 08; 34(11):1103-1104. View abstract
  11. Ney DM, Stroup BM, Clayton MK, Murali SG, Rice GM, Rohr F, Levy HL. Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial. Am J Clin Nutr. 2016 Aug; 104(2):334-45. View abstract
  12. Levy HL. The remarkable S. Harvey Mudd - A reminiscence. Mol Genet Metab. 2016 07; 118(3):143-4. View abstract
  13. Rajabi F, Levy HL. Hyperphenylalaninemia and the genomic revolution. Mol Genet Metab. 2015 Mar; 114(3):380-1. View abstract
  14. Rohr F, Wessel A, Brown M, Charette K, Levy HL. Adherence to tetrahydrobiopterin therapy in patients with phenylketonuria. Mol Genet Metab. 2015 Jan; 114(1):25-8. View abstract
  15. Hecht LE, Wessel AE, Levy HL, Berry GT. The complexity of newborn screening follow-up in phenylketonuria. JIMD Rep. 2014; 17:37-9. View abstract
  16. Wessel AE, Mogensen KM, Rohr F, Erick M, Neilan EG, Chopra S, Levy HL, Gray KJ, Wilkins-Haug L, Berry GT. Management of a Woman With Maple Syrup Urine Disease During Pregnancy, Delivery, and Lactation. JPEN J Parenter Enteral Nutr. 2015 Sep; 39(7):875-9. View abstract
  17. Camp KM, Parisi MA, Acosta PB, Berry GT, Bilder DA, Blau N, Bodamer OA, Brosco JP, Brown CS, Burlina AB, Burton BK, Chang CS, Coates PM, Cunningham AC, Dobrowolski SF, Ferguson JH, Franklin TD, Frazier DM, Grange DK, Greene CL, Groft SC, Harding CO, Howell RR, Huntington KL, Hyatt-Knorr HD, Jevaji IP, Levy HL, Lichter-Konecki U, Lindegren ML, Lloyd-Puryear MA, Matalon K, MacDonald A, McPheeters ML, Mitchell JJ, Mofidi S, Moseley KD, Mueller CM, Mulberg AE, Nerurkar LS, Ogata BN, Pariser AR, Prasad S, Pridjian G, Rasmussen SA, Reddy UM, Rohr FJ, Singh RH, Sirrs SM, Stremer SE, Tagle DA, Thompson SM, Urv TK, Utz JR, van Spronsen F, Vockley J, Waisbren SE, Weglicki LS, White DA, Whitley CB, Wilfond BS, Yannicelli S, Young JM. Phenylketonuria Scientific Review Conference: state of the science and future research needs. Mol Genet Metab. 2014 Jun; 112(2):87-122. View abstract
  18. Levy HL. Newborn screening: the genomic challenge. Mol Genet Genomic Med. 2014 Mar; 2(2):81-4. View abstract
  19. Landau YE, Lichter-Konecki U, Levy HL. Genomics in newborn screening. J Pediatr. 2014 Jan; 164(1):14-9. View abstract
  20. Cederbaum S, Levy HL. Is melatonin synthesis a new biomarker for the pathogenesis and treatment of phenylketonuria? J Pediatr. 2013 May; 162(5):893-4. View abstract
  21. Levy HL. Congenital heart disease in maternal PKU. Mol Genet Metab. 2012 Dec; 107(4):648-9. View abstract
  22. Saranjam H, Chopra SS, Levy H, Stubblefield BK, Maniwang E, Cohen IJ, Baris H, Sidransky E, Tayebi N. A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders. Eur J Hum Genet. 2013 Jan; 21(1):115-7. View abstract
  23. Waisbren SE, Potter NL, Gordon CM, Green RC, Greenstein P, Gubbels CS, Rubio-Gozalbo E, Schomer D, Welt C, Anastasoaie V, D'Anna K, Gentile J, Guo CY, Hecht L, Jackson R, Jansma BM, Li Y, Lip V, Miller DT, Murray M, Power L, Quinn N, Rohr F, Shen Y, Skinder-Meredith A, Timmers I, Tunick R, Wessel A, Wu BL, Levy H, Elsas L, Berry GT. The adult galactosemic phenotype. J Inherit Metab Dis. 2012 Mar; 35(2):279-86. View abstract
  24. Levy HL. Newborn screening conditions: What we know, what we do not know, and how we will know it. Genet Med. 2010 Dec; 12(12 Suppl):S213-4. View abstract
  25. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010 Oct 23; 376(9750):1417-27. View abstract
  26. Yusupov R, Finegold DN, Naylor EW, Sahai I, Waisbren S, Levy HL. Sudden death in medium chain acyl-coenzyme a dehydrogenase deficiency (MCADD) despite newborn screening. Mol Genet Metab. 2010 Sep; 101(1):33-9. View abstract
  27. Marsden D, Levy H. Newborn screening of lysosomal storage disorders. Clin Chem. 2010 Jul; 56(7):1071-9. View abstract
  28. Levy H, Burton B, Cederbaum S, Scriver C. Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH(4)) in phenylketonuria and its use in treatment. Mol Genet Metab. 2007 Dec; 92(4):287-91. View abstract
  29. Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz FK, Whitley CB, Feillet F, Feigenbaum AS, Bebchuk JD, Christ-Schmidt H, Dorenbaum A. Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study. Lancet. 2007 Aug 11; 370(9586):504-10. View abstract
  30. Waisbren SE, Noel K, Fahrbach K, Cella C, Frame D, Dorenbaum A, Levy H. Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab. 2007 Sep-Oct; 92(1-2):63-70. View abstract
  31. Dobrowolski SF, Ellingson C, Coyne T, Grey J, Martin R, Naylor EW, Koch R, Levy HL. Mutations in the phenylalanine hydroxylase gene identified in 95 patients with phenylketonuria using novel systems of mutation scanning and specific genotyping based upon thermal melt profiles. Mol Genet Metab. 2007 Jul; 91(3):218-27. View abstract
  32. Wattanasirichaigoon D, Khowsathit P, Visudtibhan A, Suthutvoravut U, Charoenpipop D, Kim SZ, Levy HL, Shih VE. Pericardial effusion in primary systemic carnitine deficiency. J Inherit Metab Dis. 2006 Aug; 29(4):589. View abstract
  33. Marsden D, Larson C, Levy HL. Newborn screening for metabolic disorders. J Pediatr. 2006 May; 148(5):577-584. View abstract
  34. Smith SE, Kinney HC, Swoboda KJ, Levy HL. Subacute combined degeneration of the spinal cord in cblC disorder despite treatment with B12. Mol Genet Metab. 2006 Jun; 88(2):138-45. View abstract
  35. Lawson-Yuen A, Levy HL. The use of betaine in the treatment of elevated homocysteine. Mol Genet Metab. 2006 Jul; 88(3):201-7. View abstract
  36. James PM, Levy HL. The clinical aspects of newborn screening: importance of newborn screening follow-up. Ment Retard Dev Disabil Res Rev. 2006; 12(4):246-54. View abstract
  37. Browning MF, Levy HL, Wilkins-Haug LE, Larson C, Shih VE. Fetal fatty acid oxidation defects and maternal liver disease in pregnancy. Obstet Gynecol. 2006 Jan; 107(1):115-20. View abstract
  38. Levy HL. Metabolic disorders in the center of genetic medicine. N Engl J Med. 2005 Nov 03; 353(18):1968-70. View abstract
  39. Sahai I, Baris H, Kimonis V, Levy HL. Krabbe disease: severe neonatal presentation with a family history of multiple sclerosis. J Child Neurol. 2005 Oct; 20(10):826-8. View abstract
  40. Waisbren SE, Rones M, Read CY, Marsden D, Levy HL. Brief report: Predictors of parenting stress among parents of children with biochemical genetic disorders. J Pediatr Psychol. 2004 Oct; 29(7):565-70. View abstract
  41. Waisbren SE, Levy HL. Expanded screening of newborns for genetic disorders. JAMA. 2004 Feb 18; 291(7):820-1; author reply 821. View abstract
  42. Koch R, Azen C, Friedman E, Hanley W, Levy H, Matalon R, Rouse B, Trefz F, Ning J, de la Cruz F. Research design, organization, and sample characteristics of the Maternal PKU Collaborative Study. Pediatrics. 2003 Dec; 112(6 Pt 2):1519-22. View abstract
  43. Levy HL. Historical background for the maternal PKU syndrome. Pediatrics. 2003 Dec; 112(6 Pt 2):1516-8. View abstract
  44. Levy HL, Waisbren SE, Güttler F, Hanley WB, Matalon R, Rouse B, Trefz FK, de la Cruz F, Azen CG, Koch R. Pregnancy experiences in the woman with mild hyperphenylalaninemia. Pediatrics. 2003 Dec; 112(6 Pt 2):1548-52. View abstract
  45. Koch R, Hanley W, Levy H, Matalon K, Matalon R, Rouse B, Trefz F, Güttler F, Azen C, Platt L, Waisbren S, Widaman K, Ning J, Friedman EG, de la Cruz F. The Maternal Phenylketonuria International Study: 1984-2002. Pediatrics. 2003 Dec; 112(6 Pt 2):1523-9. View abstract
  46. Güttler F, Azen C, Guldberg P, Romstad A, Hanley WB, Levy HL, Matalon R, Rouse BM, Trefz F, de la Cruz F, Koch R. Impact of the phenylalanine hydroxylase gene on maternal phenylketonuria outcome. Pediatrics. 2003 Dec; 112(6 Pt 2):1530-3. View abstract
  47. Waisbren SE, Albers S, Amato S, Ampola M, Brewster TG, Demmer L, Eaton RB, Greenstein R, Korson M, Larson C, Marsden D, Msall M, Naylor EW, Pueschel S, Seashore M, Shih VE, Levy HL. Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress. JAMA. 2003 Nov 19; 290(19):2564-72. View abstract
  48. Levy HL. Lessons from the past--looking to the future. Newborn screening. Pediatr Ann. 2003 Aug; 32(8):505-8. View abstract
  49. Toone JR, Applegarth DA, Levy HL, Coulter-Mackie MB, Lee G. Molecular genetic and potential biochemical characteristics of patients with T-protein deficiency as a cause of glycine encephalopathy (NKH). Mol Genet Metab. 2003 Aug; 79(4):272-80. View abstract
  50. Harvey Mudd S, Braverman N, Pomper M, Tezcan K, Kronick J, Jayakar P, Garganta C, Ampola MG, Levy HL, McCandless SE, Wiltse H, Stabler SP, Allen RH, Wagner C, Borschel MW. Infantile hypermethioninemia and hyperhomocysteinemia due to high methionine intake: a diagnostic trap. Mol Genet Metab. 2003 May; 79(1):6-16. View abstract
  51. Picker JD, Puga AC, Levy HL, Marsden D, Shih VE, Degirolami U, Ligon KL, Cederbaum SD, Kern RM, Cox GF. Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. J Pediatr. 2003 Mar; 142(3):349-52. View abstract
  52. Fearing MK, Levy HL. Expanded newborn screening using tandem mass spectrometry. Adv Pediatr. 2003; 50:81-111. View abstract
  53. Fowler DJ, Picker J, Waisbren SE, Levy HL. Neonatal screening for medium--chain acyl-CoA dehydrogenase deficiency. Lancet. 2002 Feb 16; 359(9306):628. View abstract