Hi Tom,
My first reaction upon seeing that PHA 1 was autosomal dominant was exactly like yours, i.e. your son couldn’t possibly have it if both his parents are alive and kicking. However, in taking a quick look through Pub-Med, it does appear that it is entirely possible to have PHA 1 and be completely asymptomatic. Odd, but apparently true. I’ll paste in a couple of those references below. One of the articles is even fittingly titled, "The Enigma of PHA."
Looked at another way, I suppose you could wonder the same thing about the parents of the children who HAVE been diagnosed with PHA 1, i.e. how did they manage to live through infancy to pass this condition on to their children, or live long enough to have children, in the first place? Since all the subjects in the documented cases are now older than your son, it seems reasonable to conclude that their parents are older than you and your wife---or at least contemporaries---so you could probably say the same thing about lack of testing available, unsophisticated medical care, etc., when they were growing up. It sounds like most of these parents were not cases detected and successfully treated at birth...but rather folks who were asymptomatic and did not know they carried genes for this condition until their children were later diagnosed with the illness.
Please don’t get me wrong---I am not trying to "push" this idea on you. It’s for your doctors to make the case for a specific diagnosis. I’m just trying to point out that being asymptomatic apparently doesn’t preclude one from having PHA 1, even if it is autosomal dominant. Also, I do agree with you completely that what your son has is not mild.
As far as genetic testing: Before trying to figure out where best to get genetic testing, I think the doctors really need to narrow down a diagnosis first. The problem is that if you don’t know what it is you’re looking for, or if you start out with the wrong hypothesis, the genetic testing will be pretty useless. It’ll tell you what your child DOESN’T have, but it won’t tell you what your child DOES have.
Once you know with more certainty what it is you’re trying to find, you’ll be able to figure out which lab or which doctor might be the most qualified to evaluate that particular condition.
***************************************************************
| 1: J Clin Endocrinol Metab 1990 Mar;70(3):638-41 | Related Articles,[unauthorised script deleted] language=JavaScript1.2> Links |
Pseudohypoaldosteronism in eight families: different forms of inheritance are evidence for various genetic defects.
Kuhnle U, Nielsen MD, Tietze HU, Schroeter CH, Schlamp D, Bosson D, Knorr D, Armanini D.
University of Munich, Children’s Hospital, West Germany.
Pseudohypoaldosteronism is a rare hereditary disorder presenting in early infancy with renal salt loss leading to hyponatremia and hyperkalemia despite high levels of plasma aldosterone. The patients are insensitive to mineralocorticoids; however, sodium supplementation is able to correct electrolyte abnormalities. Absent or greatly diminished type I aldosterone receptors in peripheral mononuclear leucocytes have been recently demonstrated and explain the lack of response to mineralocorticoids. We have studied the mode of inheritance in eight families with a total of nine patients. There was evidence for an autosomal recessive form of inheritance in four families, while the other four families appeared to have an autosomal dominant mode of transmission. In three families the autosomal recessive form was characterized by normal receptor as well as hormone data in both parents, while in one family receptor levels in both parents were greatly reduced, but hormone levels were normal. In the four families with an autosomal dominant mode of transmission there was always one parent with reduced receptor binding in peripheral mononuclear leucocytes and elevated serum hormone levels. These parents were entirely asymptomatic. In an extended family we were able to study an aunt and her newborn daughter, who were both also biochemically affected but clinically asymptomatic. It, therefore, appears that this dual pattern of genetic transmission may indicate differing genetic defects which cause the same clinical picture of pseudohypoaldosteronism.
***************************************************************
The enigma of pseudohypoaldosteronism.
Zennaro MC, Borensztein P, Soubrier F, Armanini D, Corvol P.
INSERM U36, College de France, Paris.
The syndrome of primary pseudohypoaldosteronism (PHA) is a hereditary disease characterized by increased aldosterone secretion associated with clinical signs of hypoaldosteronism. These include salt wasting and failure to thrive in the newborn, high urinary sodium, hyponatremia, hyperkalemia, and metabolic acidosis. Plasma renin activity is usually elevated in association with aldosterone. The clinical manifestation of the disease is variable, including severely affected patients who may die in infancy and patients who are asymptomatic. The disease seems to result from a cellular resistance to mineralocorticoid action, which could be either generalized, or restricted to the kidney. The condition is inherited as an autosomal dominant or an autosomal recessive trait; however, sporadic cases have been described. In this paper we report a 20-year follow-up study of a French family affected by PHA and we discuss the pathogenesis of the disease.
PMID: 8191555 [PubMed - indexed for MEDLINE]
*******************************************************************