Connecting the PWS Dots | ResearchNotes | Elevated Phenylalanine And Tyrosine

Research Notes: Elevated Phenylalanine and Tyrosine in PWS

Two of the children with PWS that I've reviewed lab test results for had plasma amino acid profiles performed. A two-month-old infant had normal plasma tyrosine (85, reference range: 0-150 umol/L), but the other, a neonate in the NICU, had elevated tyrosine (105, reference range: 20-96). Neither child had plasma phenylalanine outside of reference range.

A 1989 study by Butler (Am J Hum Genet. 1989 Jul. Hypopigmentation: a common feature of Prader-Labhart-Willi syndrome.) noted that -

"An error in amino acid metabolism (e.g., phenylalanine and tyrosine, which are utilized in melanin production) may exist in PLWS, as supported by low tyrosinase activity, albinism (Wiesner et al. 1987; Phelan et al. 1988), and tyrosinemia (Fernhoff et al. 1984)."

The Butler study found that 43% (10/23) of those with PWS for which data was available had plasma phenylalanine and/or tyrosine levels that were outside of reference ranges. The cases included those with PWS due to both deletion and non-deletion (i.e., presumably due to UPD or IC defects) and the age range for those with high phenylalanine and/or tyrosine was 3-24 years, which indicates the cause was not transient tyrosinemia of infancy or muscle catabolization during the neonatal period.

The table below is comprised of data extracted from a table in the Butler study and, aside from showing that 43% of those with PWS had phenylalanine and/or tyrosine levels that were outside of reference ranges, also shows that -

39% (9) had elevated phenylalanine and/or tyrosine.
34.7% (8) had elevated plasma phenylalanine.
8.7% (2) had low plasma phenylalanine.
17% (4) had elevated tyrosine; three of those four also had elevated phenylalanine.
8.7% (2) had elevated phenylalanine and high normal tyrosine

Although the levels of phenylalanine and tyrosine are not as high as are found in phenylketonuria (PKU), tyrosinemia, or clinically significant hyperphenylalaninemia, they do indicate the existence of an impairment in the metabolizing of phenylalanine and tyrosine in a significant number of those with PWS that seems worthy of further investigation.

Plasma Phenylalanine and Tyrosine Levels in PWS - Data Extracted from Butler 1989
	Case #	Sex	Age (yrs)	PWS Type	Phenylalanine [38-78 nmol/ml]	Tyrosine [33-91 nmol/ml]
1	2	M	4.0	del	82	100
2	5	M	12.0	del	70	47
3	7	M	14.0	del	62	71
4	10	M	18.0	del	69	79
5	12	M	18.0	del	57	55
6	13	M	20.0	del	37	39
7	15	F	5.0	del	84	87*
8	16	F	5.0	del	72	101
9	20	F	16.0	del	65	65
10	23	F	20.0	del	101	111
11	24	F	20.0	del	75*	59
12	26	M	23.0	del	35	46
13	29	F	35.0	del	53	41
14	33	M	7.0	not del	96	88*
15	37	M	11.0	not del	89	100
16	40	M	19.0	not del	54	46
17	41	M	20.0	not del	48	53
18	42	M	24.0	not del	87	66
19	43	F	3.0	not del	90	70
20	45	F	11.0	not del	68	58
21	47	F	14.0	not del	106	81
22	49	F	16.0	not del	39*	53
23	50	F	17.0	not del	53	55

Pathway map showing fumarate as an end-product of tyrosine metabolism. Interestingly, some children respond extremely well to the fumarate chelate of L-carnitine (L-carnitine fumarate). (Graphic from Pediatrics. 2006 May. Stacpoole, et al. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children.)